SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

SARS-CoV-2, the causal agent of the globally spreading COVID-19, is capable of infecting variable animals besides human being. We evaluated the potential susceptibility of important livestock, pets and aquatic mammals by performing a multi-species sequence analysis of ACE2 based on the reported affected and unaffected animals. We identified a triple amino acid pattern of ACE2, at position 30, 31 and 34, that might be associated with SARS-CoV-2 infection and H34 might be an indicator of the susceptibility to COVID-19.

Global emerge of zoonotic novel corona virus (COVID-19) became a pandemic and its effect to mankind is talk of the town now a days. This tiny, invisible enemy has affected every country in the world and almost every living directly or indirectly and nationwide complete lockdown has triggered a short-term environmental impact. Since 2003, corona virus came into existence in the form of Severe Acute Respiratory Syndrome (SARS) and more evolved Middle East Respiratory Syndrome (MERS) in 2012. This time, at the end of December 2019, outbreak of novel corona virus COVID-19 (also known as SARS-CoV₂, nCoV-2019) draw attention as global health emergency. World Health Organization (WHO) report says that the outbreak of this virus is so immense, it has already affected 35,57,235 people and caused death to 2,45,150 people worldwide and 46,433 Indians got affected with 1568 death as on 5^th May 2020 (2:00 am) and these numbers are increasing exponentially day by day. Virologist, micro-biologist and science community are hammering their head very hard to find out cure and vaccine against this powerful virus and to prevent mass demise of mankind. In order to curb the spread of COVID-19, Janta curfew on 22.03.2020 and nationwide complete lockdown was implemented in India for 21 days (phase-I, from 25.03.2020 to 14.04.2020) to stop community transmission of third stage, for 19 days (phase-II, 15.04.2020 to 03.05.2020) and 14 days (phase-III, 04.05.2020 to 17.05.2020) complete lockdown to minimize the community transmission effect. During complete lockdown and quarantine period a drastic change in Earth’s atmosphere, including reduction in emission of greenhouse gases, air pollution (~50% fall in air quality index), noise pollution, water pollution and solid waste pollution, have been recorded by government agencies as well as private agencies. In this paper we considered data of Janta curfew, phase-I and phase-II lockdown to link between geological and environmental aspect related to environmental impact due to emerge of COVID-19 and massive reduction in pollution level during complete lockdown in India. We propose future lockdown strategies to minimize the emission of greenhouse gas by ~100 Mt to ~200Mt (3.33% to 6.66%) of GHG_total per year by 2-4 days per month nationwide lockdown or ~70 Mt to ~140 Mt (2.33% to 4.66%) of GHG_total per year by 2-4 days per month complete lockdown of energy sectors only.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine for other potential interactions between the virus and other cell receptors. Based on the clinical observation of low smoking prevalence among hospitalized COVID-19 patients, we recently identified a “toxin-like” amino acid (aa) sequence on the receptor binding domain of the spike glycoprotein of SARS-CoV-2 (aa 375-390) with homology to a sequence of a snake venom toxin, which could interact with nicotinic acetylcholine receptors (nAChRs). We now present computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 spike glycoprotein and the extracellular domain of the nAChR alpha9 subunit. We identified an interaction between the aa381-386 of the SARS-CoV-2 spike glycoprotein and the aa189-192 of the extracellular domain of the nAChR alpha9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the alpha9 nAChR and alpha-bungarotoxin. A similar interaction was observed between the pentameric alpha7 AChR and the SARS-CoV-2 spike glycoprotein. Our findings support the hypothesis that severe COVID-19 may be associated with disruption of the nicotinic cholinergic system which could be caused by an interaction between SARS-CoV-2 and nAChRs.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

An important stage in SARS-CoV-2 life cycle is the fusion of spike(S) protein with the ACE2 host-cell receptor. Therefore, to explore conserved features in S protein dynamics and to identify potentially novel regions for drugging, we measured variability derived from 791 viral genomes and studied its properties by MD simulation. The findings indicated that S2 subunit (HR1, CH, and CD domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the RBD domain, which is typically targeted in drug discovery programmes, exhibits more sequence variability and flexibility. Interpretations from MD suggest that the monomer is in constant motion showing transitions up-to-down state, and the trimer cavity may function as a 'bouncing spring' that may facilitates S protein interactions with ACE2. Feasibility of trimer cavity for potential drug target was examined by SBVS screening. Several hits that have already been validated or suggested to inhibit the SARS-CoV-2 virus in cell systems were identified; in particular, the data suggest an action mechanism for such molecules including Chitosan and macrolide types. These findings identify a novel binding-site formed by the S protein, that might assist in future drug discovery programmes aimed at targeting the CoV family of viruses.

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

SARS CoV-2 or COVID-19 pandemic global-outbreak created the most unstable situation of human health-economy. Last two decades different parts of the word experienced smaller or bigger outbreak related to human-coronaviruses. The spike-glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting-enzyme (ACE-2) and transit over a stabilized open-state for the viral-internalization to the host-cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less-sensitive to the protein/nucleic-acid based-drugs. In this emergent situation, drug-induced destabilization of spike-binding to RBD could be a good strategy. In the current study we demonstrated by Bioinformatics (CASTp: Computed-Atlas-of-Surface-Topography, PyMol: molecular-visualization) and Molecular docking (PatchDock) experiments that tea flavonoids catechin-products mainly EGCG or other like theaflavin gallate demonstrated higher Atomic Contact Energy (ACE), surface area and more amino-acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike-protein. Moreover, out of three distinct binding-sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the vCoV-RBD of ACE2 contact), EGCG and TG bind all three sites. As because site I and II is in closer contact with open state location and viral-host contact area so these drugs might have significant effects. Taking into account the toxicity/side-effects by CQ/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation etc. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, M^pro of the COVID-19 virus. With the high-resolution X-ray crystallography structure of this viral enzyme recently being solved, CADD provides a veritable tool for rapidly screening diverse sets of compounds with the aim of identifying ligands capable of forming energetically favorable complexes with M^pro . From our screening of 1,082,653 compounds derived from the ZINC, the DrugBank, and our in-house African natural product libraries, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective M^pro inhibitors, which include FDA-approved drugs, drug candidates in clinical trials, as well as natural products. The top-ranking compounds are characterized by the presence of an extended ring system combined with functional groups that allow the ligands to adapt flexibly to the M^pro active site as, for example, present in the biflavonoid amentoflavone, one of the most promising compounds identified here. This particular chemical architecture leads to considerable stronger binding than found for reference compounds with in vitro demonstrated M pro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (M^pro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 M^pro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 M^pro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 M^pro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.

The 2019 Coronavirus pandemic which was initially referred to as 2019-nCoV, was first identified in Wuhan, China. Early response from the Chinese government included quarantine of infected persons, isolation and total lockdown of Wuhan province to prevent further spread. With the spread of the disease across national borders and declaration of the disease as a global pandemic, there has been a robust response by the international community to contain this deadly virus and prevent its further spread worldwide. Africa is not left out of this rampaging pandemic with documented cases in over 40 countries and still rising. Although extensive studies have been carried out on the novel SARS-CoV-2 on its pathogenesis, mode of infection and virulence but much is still unknown. However, potentially infectious samples are received routinely in the medical laboratory for analysis. This technical note reviews good laboratory practice (GLP) and processes across the different specialities of Medical Laboratory practice that should minimize the risk of infection to laboratory staff especially in resource-limited settings.

The 2019 Novel Coronavirus (COVID-19) has caused an acute reduction in world supplies of personal protective equipment (PPE) due to increased demand. To combat the impending shortage of equipment including N95 masks, the George Washington University Hospital (GWUH) developed a 3D printed reusable N95 comparable respirator that can be used with multiple filtration units. We evaluated several candidate prototype respirator models, 3D printer filaments, and filtration units detailed here. Our most recent working model was based on a respirator found on an open source maker website and was developed with PLA (printer filament), a removable cap, a removable filtration unit consisting of two layers of MERV 16 sandwiched between MERV 13, and removable elastic bands to secure the mask. Our candidate mask passed our own suction test protocol to evaluate leakage and passed a qualitative Bitrix N95 fit test at employee health at GWUH. Further efforts are directed at improving the current model for seal against face, comfort, and sizing. The 3D model is available upon request and in the supplement of this paper. We welcome collaboration with other institutions and suggest other facilities consider mask fit for their own population when exploring this concept.

Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

The current outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 in Wuhan, China has killed more than 2600 people since December 2019. Currently there is no effective treatment for this epidemic. Drug for anti SARS-CoV-2 are urgently needed. In this study we evaluated two compound libraries containing launched drugs and compounds from 300 kinds of Traditional Chinese Medicine in order to find anti SARS-CoV-2 drugs. Docking and then calculating binding free energy were performed as workflow against four key anti-SARS-CoV-2 drug targets, 3CLpro, PLpro and RdRp from SARSCoV-2, and AAK1 from human as well. As a result, drugs launched with potential for antiviral usage were selected in the hope of providing some knowledge for future drug discovery.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

The SARS-CoV-2 was confirmed to cause the regional outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. The 3C-like protease (3CL^pro), an essential enzyme for viral replication, is a valid target to compacts SARS-CoV and MERS-CoV. In this research, an integrated library consisting of 1000 compounds from Asinex Focused Covalent (AFCL) library and 16 FDA-approved protease inhibitors were screened against SARS-CoV-2 3CL^pro. Top compounds with significant docking scores and making stable interactions with catalytic dyad residues were obtained. The screening results in identification of compound 621 from AFCL library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of SARS-CoV-2 3CL^pro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CL^pro were characterized using 50 nanoseconds (ns) molecular dynamic (MD) simulation approach. The identified compounds are potential inhibitors worthy of further development as SARS-CoV-2 3CLpro inhibitors/drugs. Importantly, the identified FDA-approved therapeutics could be ready for clinical trials to treat infected patients and help to curb the COVID-19.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

During the coronavirus disease 2019 (COVID-19) pandemic, individuals with immune-mediated inflammatory diseases (IMIDs), such as systemic lupus erythematosus and rheumatoid arthritis, face a heightened risk of infection and severe outcomes due to immunological alterations resulting from their underlying conditions and immunosuppressive treatments. Even as the pandemic has transitioned to an endemic state, it remains crucial to recognize that these patients continue to be at risk. In this narrative review, we analyzed existing literature to explore the impact of IMIDs, clinical risk factors, and the influence of immunosuppressive therapies on COVID-19-related risks and outcomes. Notably, certain disease-modifying antirheumatic drugs (DMARDs), like rituximab, are associated with worse COVID-19 outcomes, and rituximab-treated patients show impaired immune responses to COVID-19 vaccination. Additionally, we outline the diverse effects of glucocorticoids on COVID-19 outcomes and management. To highlight real-life challenges faced by clinicians caring for patients with IMIDs, we present an illustrative scenario that underscores the importance of effective vaccination, timely boosting, and additional mitigation strategies against COVID-19. Given the clinical heterogeneity and diverse disease states within IMIDs, it is crucial to understand the ongoing implications and risks associated with COVID-19 in these patients, to guide the implementation of appropriate measures and optimize care and outcomes in the current endemic era.

Myocarditis has been recognized as a possible rare complication of COVID-19 mRNA vaccination. It concerns between one and five vaccinated people per 100,000 in the general population, with increased incidence in adolescent and young adult men. Most often, cases of myocarditis have been reported in the days following the second dose of vaccine mainly in younger male patients. This rare complication of vaccination usually resolves within days or weeks. However, the pathophysiological events responsible for the increase in frequency of myocarditis after COVID-19 vaccination remain unclear. Several recent reports have highlighted that free spike proteins circulating in the blood of patients at high levels appear to play a major role in myocarditis. Here, we review the most relevant data that partly lift the veil on the molecular mechanisms of the induction of myocarditis following mRNA-based COVID-19 vaccination. We hypothesize that a mechanism of molecular mimicry of the viral spike triggers transient dysregulation of angiotensin-converting enzyme 2, leading to increased soluble angiotensin II binding to the transmembrane receptor angiotensin II type I receptor, similar to what is observed during SARS-CoV-2 infection. We suggest to standardize management of suspected cases of mRNA-based COVID-19 vaccine-induced myocarditis, including angiotensin II and spike antigenemia monitoring.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

At present Coronavirus disease-2019 (COVID-19) is one of the leading contributing factor to mortality and the impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on the sinonasal tract has become more prominent, particularly with the rising awareness of olfactory dysfunction (OD). We extracted data from published papers available in electronic databases (Wiley online library, PubMed, and Nature). We used the following search terms alone or with combinations - Olfactory dysfunction, SARS-CoV-2, mechanism and treatments. We found worldwide up to 98% of patients confirmed OD due to COVID-19. Current studies have implied that regardless of the high self-reported recovery rate, 25–40% of patients after 1 or 2 months and approximately 15%–28% of patients at six months struggle to fully restore their sense of smell. Moreover, female sex, younger and older age, active smoking, and chronic lung disease are reported as the associated risk factors of OD. Although the pathophysiological mechanism of action(s) of the OD is yet to be explored in depth, central nervous system (CNS) entrance, olfactory bulb (OB) and sustentacular cell damage, neural routes inflammation, non-neuronal cells damage, decreased OB volume and deregulation of olfactory receptor genes are among the commonly reported mechanisms for the development of OD.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

Background: In March 2020, a COVID-19 outbreak associated with the Falles Festival in Borriana, Spain, led to significant infections. Methods: In June 2022, we conducted a cross-sectional follow-up study of 473 socially engaged adults aged 18 to 64, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse weighted probability analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count. Results: 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Not complying with long COVID criteria associated with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ‐producing‐CD8+ response, and infection during the Omicron period. Conversely, increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56.4% to 91.7%) and symptom count by 55.2% (95% CI: 31.6% to 78.7%). Conclusion: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination’s role in mitigating SARS-CoV-2 infection consequences.

Hypertension is one of the most common and significant cardiovascular risk factor. With the emergence of COVID-19, concerns have arisen about its potential to exacerbate cardiovascular morbidity and mortality. Several theories have emerged linking hypertension with COVID-19. However, the relationship between SARS-CoV-2 infection and long-term risk of hypertension remains insufficiently explored. Therefore, our study aimed to investigate the impact of COVID-19 infection on blood pressure and long-term risk of hypertension developing. A comprehensive search was conducted in the PubMed and SCOPUS databases up to 10th August 2023 for relevant papers. The analysis included 35 eligible articles. The majority of the latest studies pointed to increase BP after COVID-19 infection. However, several observations contradicted the influence of SARS-CoV-2 on the hypertension development or suggesting a transient effect. The possible role of the loss of angiotensin-converting enzyme 2, cytokine storm, increased sympathetic activity, and endothelial dysfunction were considered. On the other hand, BP changes following COVID-19 could be a consequence of lifestyle changes, which often accompanied COVID-19 infection. Our findings highlight the urgent need for comprehensive research on the COVID-19 and hypertension link. These insights are crucial for implementing effective prevention and management strategies for individuals with the history of COVID-19 infection.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

Results from an explorative study revealing spatio-temporal patterns of the SARS-CoV-2/COVID-19 epidemic in Germany are presented. We dispense with contestable model assumptions and show the intrinsic spatio-temporal patterns of the epidemic dynamics. The analysis is based on COVID-19 incidence data, which are age-stratified and spatially resolved at the county level, provided by the Federal Government’s Public Health Institute of Germany (RKI) for public use. Although the 400 county-related incidence time series show enormous heterogeneity both with respect to temporal features as well as spatial distributions, the counties’ incidence curves organise into well distinguished clusters that coincide with East and West Germany. The analysis is based on dimensionality reduction, multidimensional scaling, network analysis, and diversity measures. Dynamical changes are captured by means of difference-in-difference methods which are related to fold changes of the effective reproduction numbers. The age-related dynamical patterns suggest a considerably stronger impact of children, adolescents and seniors on the epidemic activity than previously expected. Besides these concrete interpretations, the work mainly aims at providing an atlas for spatio-temporal patterns of the epidemic which serves as a basis to be further explored with the expertise from different disciplines, particularly sociology and policy makers. The study should also be understood as a methodological contribution to getting a handle on the unusual complexity of the COVID-19 pandemic.

The COVID-19 pandemic has led to a significant and enduring influence on global health, in-cluding maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above hiatus, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women, immediately after term delivery, of which seven had confirmed SARS-CoV-2 in-fection by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We extracted total RNA from placental tissues, separately from maternal and fetal compartments, constructed cDNA li-braries, and sequenced them to assess mRNA and small RNA expression. Our analysis revealed 727 differentially expressed genes (DEG) in the maternal placental tissue, with 608 upregulated and 109 downregulated in SARS-CoV-2-positive women compared with healthy, negative wom-en. In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. Specifically, we observed significant downregulation of seven genes belonging to the pregnancy-specific glycoprotein (PSG), related to the immunoglobulin superfam-ily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28, FDR ≤ 0.05). Additionally, comparing symptomatic women with healthy, we identified 14,223 DEGs, with high expression of the inflammatory cytokine IL6 in the maternal placenta of the symptomatic women. Furthermore, KEGG analysis revealed that pathways relat-ed to viral infection, vascular smooth muscle contraction, and oxytocin signaling were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risk of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta’s anti-viral effects in ma-ternal SARS-CoV-2 infection.

Despite the fact that COVID-19 treatment and management are now considerably regulated, SARS-CoV-2 is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component) have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Abundant resources and excellent antiviral performance make natural products a relatively cheap and easily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

The COVID-19 pandemic has posed a significant global threat, leading to several initiatives for its control and management. One such initiative involves wastewater-based epidemiology, which has gained attention for its potential to provide early warning of virus outbreaks and real-time information on its spread. In this study, water samples from two wastewater treatment plants (WWTPs) located at the south east of Spain (Region of Murcia) namely Murcia, and Cartagena, were analyzed by RT-qPCR, Phylogenetic Analysis, and Machine Learning Approach. The aim was to determine whether SARS-CoV-2 detection in the WWTPs of these two cities could serve as a proxy for the virus's spread in the population. The results confirmed that the levels of SARS-CoV-2 in these wastewater samples changed concerning the number of SARS-CoV-2 cases detected in the population and variant occurrences were in line with clinical reported data. Additionally, the phylogenetic analysis showed that samples obtained in close sampling times exhibited a higher similarity than those obtained more distantly in time. A second analysis using a machine learning approach based on the mutations found in the SARS-CoV-2 spike protein was also conducted. Hierarchical Clustering (HC) was used as an efficient unsupervised approach for data analysis. Results indicated that samples obtained in October 2022 in Murcia and Cartagena were significantly different, which corresponded well with the different virus variants circulating in the two locations. The proposed methods in this study are adequate for comparing the Accumulated Natural Vector (ANV) of the SARS-CoV-2 sequences as a preliminary evaluation of potential changes in the variants that are circulating in a given population at a specific time point.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on immune system. There was a high incidence of COVID-19 induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity, long-term disability, and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show a significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF.

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Evolution of SARS-CoV-2 has followed similar trends as other RNA viruses, e.g., HIV-1 and influenza A. Rapid initial diversification was followed by strong competition and rapid succession of dominant variants. Host-initiated RNA editing has been the primary mechanism for introducing mutations. A significant number of mutations were detrimental and were quickly purged. Fixed mutations are mostly diversifying mutations selected for host adaptation and immune evasion, with the latter accounting for more of the changes. However, immune evasion often comes at the cost of functionality, so that optimal functionality is still far from being accomplished. Instead, selection for antibody-escaping variants and accumulation of near-neutral mutations has led to suboptimal codon usage and reduced replicative capacity as demonstrated in non-respiratory cell lines. Beneficial adaptation of the virus includes reduced infectivity in lung tissues and increased tropism for the upper airway, resulting in shorter incubation periods, milder diseases, and more efficient transmission between people.

Background: After its initial detection in Wuhan, China, in December 2019, SARS-CoV-2 has spread rapidly, causing successive epidemic waves worldwide. This study aims to provide a genomic epidemiology of SARS-CoV-2 in Burkina Faso. Methods: Three hundred and seventy-seven SARS-CoV-2 genomes obtained from PCR-positive nasopharyngeal samples (PCR cycle threshold score <35) collected between May 5, 2020, and January 31, 2022 were analysed. Genomic sequences were assigned to phylogenetic clades using NextClade and to Pango lineages using pangolin. Phylogenetic and phylogeographic analyses were performed to determine the geographical sources and time of virus introduction in Burkina Faso. Results: The analyzed SARS-CoV-2 genomes could be assigned to 10 phylogenetic clades and 27 Pango lineages already described worldwide. Our analyses revealed the important role of cross-border human mobility in the successive SARS-CoV-2 introductions in Burkina Faso from neighboring countries. Conclusion: This study provides additional insights into the genomic epidemiology of SARS-CoV-2 in West Africa. It highlights the importance of land travel in the spread of the virus and the need to rapidly implement preventive policies. Regional cross-border collaborations and the adherence of the general population to government policies are key to prevent new epidemic waves.

Recent lines of evidence suggest the intriguing hypothesis that consuming common culinary herbs of the mint family might help prevent or treat Covid. Individual citizens could easily explore the hypothesis using ordinary kitchen materials. I offer a philosophical framework to account for the puzzling lack of public health messaging about this interesting idea.

Coronavirus is a disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic in 2019 from Wuhan, China. Since its emergence, it has caused immense suffering to human life, 6.27 million lives have been lost, movement curtailed and social dynamics disrupted. The golden standard for getting samples for SARS-CoV-2 detection is through oral- nasopharyngeal swab, this method of sample collection is invasive and uncomfortable, thus stigmatized the general population, and thereby impeded the progress of controlling the spread through mass testing. Being a contact disease, mechanisms to encourage mass testing is key to reduce the spread. This study thus developed a complimentary sample type to test for SARS-CoV-2, the use of human feces. Fecal samples were collected from 100 asym-symptomatic individuals suspected to be infected with COVID-19, virus RNA was then extracted and profiled through Real Time Polymerase Chain Reaction (RT-qPCR). The antigen rapid diagnostic test revealed high positivity rate of 44%, but the real time polymerase chain reaction results on nasopharyngeal and fecal samples revealed a significant variation, high number of the patients tested positive with stool samples compared to the nasopharyngeal swabs, with 43 and 37%, respectively. SARS-CoV-2 virus was detected in both symptomatic and asymptomatic individuals; however, the symptomatic registered a higher positivity of 25% compared to 20% among the asymptomatic patients. Vaccination only lowered the risk of infection, fully and partially vaccinated lowered the infection level to 10% compared to 20% among the unvaccinated. Finally, gender parity in relation to COVID19 was evaluated, more females (56%) compared to males were recruited in this study, out of which (20; 43.4%) were positive, and 26 (56.6%) were negative based on fecal RT-qPCR outcomes. Based on the outcome of this study, rapid diagnostic test (Ag-RDT) however cheap and or fast does not provide accurate information, moreover, the virus does not stay longer within the Oro-nasopharyngeal region, thus the invalid or negative results, thus use of feces should be adopted as a confirmatory test to ascertain the COVID19 status of an individual.

Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.

Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and anti-viral activity, which may limit sexual transmission of infectious diseases during intercourse. We have recently discovered that PDC-109 inhibits the membrane fusion activity of influenza virus particles and significantly impairs viral infections at micromolar concentrations. Here we investigated whether the antiviral activity of PDC-109 is restricted to Influenza or if other mammalian viruses are similarly affected. We focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 19 (COVID-19), thoroughly assessing PDC-109 inhibition with SARS-CoV-2 Spike (S)-pseudotyped reporter virus particles, but also live-virus infections. Consistent with our previous publications we found significant virus inhibition, albeit accompanied by substantial cytotoxicity. Using time-of-addition experiments however, we discovered treatment regimen that enable virus suppression without affecting cell viability. We furthermore demonstrated that PDC-109 is also able to impair infections mediated by the VSV glycoprotein (VSVg) thus indicating a broad pan-antiviral activity against multiple virus species and families.

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic, however, the need for orally available antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using 5 two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were conducted three times and in triplicate. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p<0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p<0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p=0.01) and 13.08 (p<0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro.

The evolution of some epidemics, as influenza, shows common patterns both in different regions and from year to year. On the contrary, epidemics like the novel COVID-19 show quite heterogeneous dynamics and are extremely susceptible to the measures taken to mitigate their spread. In this paper we propose empirical dynamic modeling to predict the evolution of influenza in Spain’s regions. It is a non-parametric method that looks into the past for coincidences with the present to make the forecasts. Here we extend the method to predict the evolution of other epidemics at any other starting territory and we test also this procedure with Spanish COVID-19 data. We finally build influenza and COVID-19 networks to check possible coincidences in the geographical distribution of both diseases. With this, we grasp the uniqueness of the geographical dynamics of COVID-19.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD) and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD and SOT showed activity against the WT (ID50 6,295 [4,355-8,075] for BAM/ETE; 18,214 [16,248-21,365] for CAS/IMD and 456 [265-592] for SOT) and the delta (14,780 [ID50 10,905-21,020] for BAM/ETE, 63,937 [47,211-79,971] for CAS/IMD and 1,103 [843-1,334] for SOT). Notably, only SOT was active against BA.1 (ID50 200 [37-233]) while BA.2 was neutralized by CAS/IMD (ID50 174 [134-209] ID50) and SOT (ID50 20 [9-31] ID50) but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5±0.1/1.5±0.7/1.0±0.5/0.8±0.01 μM for WT/delta/BA.1/BA.2, respectively); nirmatrelvir (0.05±0.02/0.06±0.01/0.04±0.02/0.04±0.01 μM) and remdesivir (0.08±0.04/0.11±0.08/0.05±0.04/0.08±0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, however antivirals have so far remained unaffected.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

Physical distancing and wearing a face mask are key interventions to prevent COVID-19. While this remains difficult to practice for millions of firefighters in fire engines responding to emergencies, the delayed forthcoming of evidence on the physical effectiveness of such safety interventions in this setting presents a major problem. In this field experimental study, we provided initial evidence to close this gap. We examined total aerosol burden in the cabin of a fire engine whilst manipulating crew size, natural ventilation, use of FFP2 respirators and use of SCBA full-face masks during 15-minute driving periods. At the same time, we controlled for crew activity and speaking, vehicle speed, cabin air temperature, pressure and humidity. Limiting the crew size, using FFP2 respirators and not donning SCBA full-face masks was associated with a reduction of the arithmetic mean of total aerosol burden of up to 49%. Natural ventilation as tested in this study was associated with both an increase and a decrease of total aerosol burden. This study provided initial evidence on the physical effectiveness of safety interventions in fire engines to reduce potential airborne transmission of SARS-CoV-2 through aerosols. More research about the physical and clinical effectiveness of such safety interventions is needed.

Identifying the SARS-CoV-2 virus has been a unique challenge for the scientific community. In this paper, we discuss a practical solution to help guide clinicians with interpretation of the probability that a positive, or negative, COVID-19 test result indicates an infected person, based on their clinical estimate of pre-test probability of infection.The authors conducted a small survey on LinkedIn to confirm that hypothesis that that the clinical pre-test probability of COVID-19 increases relative to local prevalence of disease plus patient age, known contact, and severity of symptoms. We examined results of PPA (Positive Percent Agreement, sensitivity) and NPA (Negative Percent Agreement, specificity) from 73 individual laboratory experiments for molecular tests for SARS-CoV-2 as reported to the FIND database ¹, and for selected methods in FDA EUA submissions^2,3. Authors calculated likelihood ratios to convert pre-test to post-test probability of disease and designed an online calculator to create graphics and text to report results. Despite best efforts, false positive and false negative Covid-19 test results are unavoidable^4,5. A positive or negative test result from one laboratory has a different probability for the presence of disease than the same result from another laboratory. Likelihood ratios and confidence intervals can convert the physician or other healthcare professional’s clinical estimate of pre-test probability to post-test probability of disease. Ranges of probabilities differ depending on proven method PPA and NPA in each laboratory. We recommend that laboratories verify PPA and NPA and utilize a the “Clinician’s Probability Calculator” to verify acceptable test performance and create reports to help guide clinicians with estimation of post-test probability of COVID-19.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Purpose: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running an high risk of being infected by the SARS-CoV-2 virus. This study investigates the epidemiological, clinical and lifestyles characteristics that might play roles in the susceptibility of HCWs to COVID-19 in a hit Italian hospital. Methods:Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs which underwent a nasopharyngeal swab for SARS-CoV-2 were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. Results: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33 (9.72-13.21). Working in a COVID-19 ward, being a former smoker (vs being a person who never smoked) and BMI were positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. Conclusions: Assuming an equal accessibility and proper use of PPE of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

Evidence was brought forward in England and the USA that Black, Asian, Latino and Minority Ethnic people exhibit higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the Interferon-induced transmembrane protein 3 (IFITM3) gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. IFITM3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up to these two developments in the ongoing SARS-CoV-2 pandemic, the present study investigates a possible association between the differences in mortality of ethnic groups in England and the combined haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for 26 populations from 1000 Genomes Project and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A significant correlation (r=0.9687, p= 0.0003) was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles, suggesting that the combination of reference alleles of the specific SNPs may be implicated in more severe outcomes of COVID-19. This study calls for further focus on the role of IFITM3 variants in the mechanism of cellular invasion of SARS-CoV-2, their impact in COVID-19 severity and their possible implications in vaccination efficacy.

The role of the immune response to SARS-CoV-2 infection is not yet well known, in particular about the persistence of circulating antibodies. The aim of the study is to compare the results of two automated systems for the determination of IgG antibodies against SARS CoV-2 and to assess the time course of the IgG response after the onset of symptoms for a period longer than that evaluated to date. IgG were measured in 98 specimens of 55 subjects with COVID-19 (time from the onset of symptoms from 3 to 109 days) using the automated tests "Abbott SARS-COV-2 IgG" and the "MAGLUMI 2019-nCoV IgG". The two methods had a concordance of 91.8%, but the quantitative correlation showed very dispersed results. All the specimens resulted positive after 17 days from the onset of the synptoms. However, the median concentrations of IgG, after a rapid increase up to about 20 days, quickly decrease to about 15% of the maximum for Maglumi. The same samples measured by Architect showed a quite constant trend up to 80 day, and then an only moderate decline. The titer of IgG against SARS-CoV-2 in patients exposed to COVID-19 may significantly and rapidly decrease, with a different time-course depending on the method used for the determination.

Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is $\sim 1.59\pm 0.17$ times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2$\mathrm{=0.74}$; correlation p-value (p) of 5x10^-13$$). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

Among the many approaches to COVID-19 prevention, the possible role of diet has so far been somewhat marginal. Nutrition is very rich in substances with a potential beneficial effect on health and some of these could have an antiviral action or in any case be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of Citrus fruits and especially of the orange (Citrus sinensis), well known for its vitamin content, but less for the function of its flavonoids. Among the latter, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the SARS-CoV-2 virus. Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy both with the coronavirus "spike" protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The affinity of hesperidin for these proteins is comparable if not superior to that of common chemical antivirals. The preventive efficacy of vitamin C, at dosage attainable by diet, against viral infections is controversial, but recent reviews suggest that this substance may be useful in case of increased stress on the immune system. Finally, the reasons that suggest undertaking appropriate research on the Citrus fruits addition in the diet, as a complementary prevention and treatment of COVID-19, are discussed.

Since December 2019, a rapid increase in the number of SARS-CoV-2 (COVID-19) cases was reported worldwide, despite strict infection control and lock down measures. Current paper investigated the actual facts behind this rapid increase in the number of cases. Study of genomic sequence reveals that domestic and wild animals were likely ancestors and zoonotic source for SARS-CoVs, MERS-CoVs, and SARS-CoV-2. Strong evidence suggest that these viruses already existed and replicated in animals and humans during past several decades, exhibiting diverse mutations, evolutions and self-limiting diseases, except during outbreaks. Serious zoonotic reservoir investigations are required to investigate animal transmission of SARS-CoVs and SARS-CoV-2 to limit current pandemic. This might be the reason of increasing number of cases via animals. SARS-CoV-2 has been retrospectively isolated in different studies in August 2019, several months before Wuhan announced. Hence, there is a possibility that viruses existed, went undetected, infecting subclinically, in past several years, and SARS-CoV-2 antigens and neutralizing antibodies may have been present in humans since long time. This might be another reason of increasing number of cases by screening as mass screening and antigen or antibody testing was not carried out in the past years. Randomized controlled trials are required to investigate human to human transmission by touch, as the current evidence is limited with conflicting results. As all SARS-CoVs are basically respiratory viruses, droplet precautions and infection control measures are essential, especially for hospital staff. Increased number of SARS-CoV-2 asymptomatic, or subclinical cases are detected worldwide. This silent phase of transmission can be beneficial for humans. Lack of symptoms eventually lessen virus transmission and reduce the pathogen's long-term survival and provide humoral herd immunity up to several years. Hence, seropositivity with diverse antibodies develops against mutating SARS-CoVs which will confer strong immunity during epidemics. Strategies such as identification, contact tracing and quarantine are costly and practically difficult. Hence, asymptomatic persons can continue their work with droplet precautions and standard infection control procedures, while symptomatic or sick persons can isolate themselves in their homes without the need for strict quarantine until clinical recovery, with reduced hospital visits and minimizing chances of hospital acquired infections. RT-PCR has low sensitivity and specificity, carries a high risk of handling live virus antigens, and requires difficult protocols. As viral load also sharply declines after few days of onset of infection, this technique might overlook infection. Furthermore, SARS-CoV-2 infection may be present in blood when oropharyngeal swabs are negative by RT-PCR. Additionally, RT-PCR usually gives false negative and false positive results and must be interpreted cautiously. This might be again a reason of increasing number of cases by false positive RT-PCR reporting. Moreover, antibodies against SARS-CoVs develop robustly in serum even by reduced amount of antigens. In contrast to RT-PCR, ELISA for diagnosing antibodies against SARS-CoV-2 demonstrates 100% specificity and 100% sensitivity, even in clinically asymptomatic individuals. These antibodies can be used for serologic surveys, monitoring and screening. However, screening tests for SARS-COV-2 should be avoided in unhygienic public places by nasopharyngeal swabs, which carry a high risk of further transmission, co-infection or superinfection. Such highly infectious virus must be isolated and tested in highly sterilized laboratory. Further strict international laws and policies are required to stop the possible spread of experimental viruses, biological warfare and bioterrorism.

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

Background: It is unclear why certain countries have been more severely affected by COVID-19 than other countries. Methods: In this ecological study we compared COVID-19 mortality and incidence/100,000 as well as 4 putative explanatory factors by WHO world region. Linear regression was then used to assess the country-level predictors of COVID-19 mortality/100,000 and incidence/100,000 in 204 countries with available data. Results: COVID-19 incidence and mortality/capita were greater in Europe than other regions. This was despite a higher testing rate in Europe than other regions. Europe had an older population than all other regions and a higher prevalence of obesity than Africa, South East Asia and the Eastern Mediterranean. Country level multiple linear regression revealed positive associations between mortality/capita and testing rate, percent of the population 65 years or older, and Europe compared to Western Pacific and South East Asia (all P<0.005). Results for the analyses with cases/100,000 as outcome variable were similar. Conclusion: Our results suggest that older populations as well as other undefined regional and national factors, possibly related to efficacy of control efforts, are responsible for differences in national severity COVID-19 epidemics.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

Early detection, isolation, and management of COVID-19 patients are crucial to contain the current pandemic. The CDC in USA recently included "sudden loss of taste (dysgeusia/ageusia) and smell (anosmia/hyposmia)” as symptoms of COVID-19. If these symptoms are reliable forerunner symptoms of COVID-19, then it may facilitate early detection and containment of the disease. Hence, we systematically evaluated the contemporary evidence on dysgeusia and anosmia as trigger symptoms in COVID-19. Ovid MEDLINE, EBSCO host, and Web of Science databases were searched between December 25, 2019-May 30, 2020.Of the 13 identified records, eight (totaling 11,054 COVID-19 patients), were included, as per the selection criteria. The studies emanated mostly from the European community, as well as China, the USA, and Iran. In total, anosmia and dysgeusia symptoms were present in 74.9 % and 81.3% ambulatory as well as hospitalized, mild-to-severe cases of COVID-19 patients, respectively. The European, US, and Iran data indicate that olfactory, and gustatory symptoms appear prior to general COVID-19 symptoms in a majority of the patients. To our knowledge, this is the first systematic review analyzing the prevalence of chemosensory dysfunction in COVID-19. Further, studies are essential to evaluate their utility as harbingers of COVID-19 onset, and to establish clinical practice guidelines.

A compartmental epidemiological model with seven groups is introduced herein, to account for the dissemination of diseases similar to the Coronavirus disease 2019 (COVID-19). In its simplified version, the model contains ten parameters, four of which relate to characteristics of the virus, whereas another four are transition probabilities between the groups; the last two parameters enable the empirical modelling of the effective transmissibility, associated in this study with the cumulative number of fatalities due to the disease within each country. The application of the model to the fatality data (the main input herein) of five countries (to be specific, of those which had suffered most fatalities by April 30, 2020) enabled the extraction of an estimate for the basic reproduction number $R_0$ for the COVID-19 disease: $R_0=4.91(33)$.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

Causative agent of the viral pneumonia outbreak in the World identified as SARS-CoV2 leads to a severe respiratory illness like SARS and MERS. The pathogen spreading has turned into a pandemic dissemination and increased the mortality rate. Therefore, useful information is urgently necessary for effective control of the disease. Our study shows the existence of unvarying sequence with no mutation, including ORF1ab regions in 134 high-quality filtered genome sequences of SARS-CoV2 downloaded from the GISAID database. We have detected this sequence stability by using MAUVE analysis and pairwise alignment with Global Needleman Wunsch algorithm for each two different sequences, reciprocally. They also confirmed all these results were also with the Clustal W analysis. The first 6500 bp including ORF1ab region is an unvarying sequence. According to the highest TM-score of predicted protein structure analysis, the results showed it is very similar to spike protein of feline infectious peritonitis virus strain UU4 (PDB 6JX7) depending on amino acid sequences encoded by this unvarying region, and N-acetyl-D-glucosamine is the ligand of this protein. These results have confirmed that N-acetyl-D-glucosamine could play an important role in controlling of SARS-CoV-2. Also, our molecular docking analysis data supports a strong protein-ligand interaction of N-acetyl-D-glucosamine with spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS CoV-2. Therefore, binding of N-acetyl-D-glucosamine to these proteins could inhibit SARS CoV-2’s replication. In the present work, we have suggested providing a repurposing compound for further in vitro and in vivo studies and new insights for ongoing clinical treatments as a new strategy to control of SARS-CoV-2 infections.

Introduction: Due to the spread of SARS CoV-2 virus responsible for COVID-19 disease, there is an urgent need to analyse COVID-19 epidemic perception in Poland. This study aims to investigate social perception of coronavirus in the Internet media during the epidemic. It is a signal report highlighting the main issues in public perception and medical commutation in real time. Methods: We study the perception of COVID-19 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet on platforms: Google, Twitter, YouTube, Wikipedia and electronic media represented by Event Registry, from January 2020 to 29.04.2020 (before and after official introduction to Poland on 04.03.20). We present trend analysis with a support of natural language processing techniques. Results: We identified seven temporal major clusters of interest on the topic COVID-19: 1) Chinese, 2) Italian, 3) Waiting, 4) Mitigations, 5) Social distancing and Lockdown, 6) Anti-crisis shield, 7) Restrictions releasing. There was an exponential increase of interest when the Polish government “declared war against disease” around 11/12.03.20 with a massive mitigation program. Later on, there was a decay in interest with additional phases related to social distancing and an anti-crisis legislation act with local peaks. We have found that declarations of mitigation strategies by the Polish prime minister or the minister of health gathered the highest attention of Internet users. So enacted or in force events do not affect interest to such extent. Traditional news agencies were ahead of social media (mainly Twitter) in dissemination of information. We have observed very weak or even negative correlations between a colloquial searching term 'antiviral mask' in Google, encyclopaedic definition in Wikipedia “SARS-CoV-2” as well official incidence series, implying different mechanisms governing the search for knowledge, panic related behaviour and actual risk of acquiring infection. Conclusions: Traditional and social media do not only reflect reality, but also create it. Risk perception in Poland is unrelated to actual physical risk of acquiring COVID-19. As traditional media are ahead of social media in time, we advise to choose traditional news media for a quick dissemination of information, however for a greater impact, social media should be used. Otherwise public information campaigns might have less impact on society than expected.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Covid-19 has given a halt to all the activities in the world. Europe was most affected, followed by the United States of America. It has taken more than 350000 lives until now. In this study, we have assessed the severity of Covid-19 by analyzing the mortality rate of Covid-19 and other chronic diseases. The Covid-19 data and “death rate” data caused by other diseases were downloaded from the world health organization (WHO) website. A normalized method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths caused by Covid-19 in April 2020 have overtaken the average number of deaths caused by Cancer, Cardiovascular diseases, and other diseases in Belgium, the United Kingdom (UK), Spain, France, and Ireland. Covid-19 was found to be strongly correlated with non-communicable respiratory diseases and Cancer with correlation coefficients 0.73 and 0.67 respectively. The severity of Covid-19 in the United States of America (USA) was moderate. The severity of Covid-19 in Asian countries was found to be low. Europe showed the highest diversity in the mortality rate of Covid-19. On average, except for a few European countries, Cardiovascular diseases, cancer, and non-communicable respiratory diseases were still more lethal and caused more deaths than Covid-19.

Background: There are no known medicines or vaccines to control the COVID-19 pandemic caused by SARS-CoV-2 (nCoV). Antiviral peptides are superior to conventional drugs and may also be effective against COVID-19. Hence, we investigated the SARS-CoV-2 Spike RBD (nCoV-RBD) that interacts with hACE2 for viral attachment and entry. Methods: Three strategies and bioinformatics approaches were employed to design potential nCoV-RBD - hACE2 interaction-blocking peptides that may restrict viral attachment and entry. Firstly, the key residues interacting with nCoV-RBD - hACE2 are identified and hACE2 sequence based peptides are designed. Second, peptides from five antibacterial peptide databases that block nCoV-RBD are identified; finally, a chimeric peptide design approach is used to design peptides that can bind to key nCoV-RBD residues. The final peptides are selected based on their physiochemical properties, numbers and positions of key residues binding, binding energy, and antiviral properties. Results: We found (i) three amino acid stretches in hACE2 interact with nCoV-RBD; (ii) effective peptides must bind to three key positions of nCoV-RBD: Gly485/Phe486/Asn487, Gln493, and Gln498/Thr500/Asn501; (iii) Phe486, Gln493, and Asn501 are critical residues; (iv) AC20 and AC23 derived from hACE2 may block two key critical positions; (iv) DBP6 identified from databases can block the three sites of the nCoV-RBD interacting with one critical position Gln498; (v) seven chimeric peptides were considered promising among which cnCoVP-3, cnCoVP-4, and cnCoVP-7 are the top three; and (vi) cnCoVP-4 meets all the criteria and is the best peptide. Conclusion: All the ten peptides need experimental validation for their therapeutic efficacy.

Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.

Outbreaks of coronavirus disease 2019 (COVID-19) have been recorded in different countries across the globe. The virus is highly contagious, hence early detection, isolation, and quarantine of infected patients will play an important role in containing the viral spread. Diagnosis in a mobile lab can aid to find infected patients in time. Here, we develop a field-deployable diagnostic workflow that can reliably detect COVID-19. Instruments used in this workflow could easily fit in a mobile cabin hospital and also be installed in the community. Different steps from sample inactivation to detection were optimized to find the fastest steps and portable instruments in detection of COVID-19. Each step was compared to that of the normal laboratory diagnosis set-up. From the results, our proposed workflow (80 min) was two times faster compared to that of the normal laboratory workflow (183 min) and a maximum of 32 samples could be detected at each run. Additionally, we showed that using 1% Rewocid WK-30 could inactivate the novel coronavirus directly without affecting the overall detection results. Comparison of our workflow using an in-house assay to that of a commercially acquired assay produced highly reliable results. From the 250 hospital samples tested, there was a high concordance 247/250 (98.8%) between the two assays. The in-house assay sensitivity and specificity were 116/116 (100%) and 131/134 (97.8%) compared to that of the commercial assay. Based on these results, we believe that our workflow is fast, reliable, adaptable and most importantly, field deployable.

In the past decades, several new diseases have emerged in new geographical areas, with pathogens including Ebola, Zika, Nipah, and coronaviruses (CoVs). Recently, a new type of viral infection has emerged in Wuhan City, China, and initial genomic sequencing data of this virus does not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed as severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although Coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes such as food-borne transmission should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses such as Ebola virus, avian H7N9, SARS-CoV, or MERS-CoV, SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus may have been transferred from an animal source such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since, no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended.

Based on recent computational and experimental studies, hesperidin, a bioactive flavonoid abundant in citrus peel, stands out for its high binding affinity to the main cellular receptors of SARS-CoV-2, outperforming drugs already recommended for clinical trials. Thus, it is very promising for prophylaxis and treatment of COVID-19, along with other coexistent flavonoids such as naringin, which could help restraining the pro-inflammatory overreaction of the immune system. Controlled hydrodynamic cavitation processes showed the highest speed, effectiveness and efficiency in the integral and green aqueous extraction of flavonoids, essential oils and pectin from citrus peel waste. After freeze-drying, the extracted pectin showed high quality and excellent antioxidant and antibacterial activities, attributed to flavonoids and essential oils adsorbed and concentrated on its surface. This study reviews the recent evidence about hesperidin as a promising molecule, and proposes a feasible and affordable process based on hydrodynamic cavitation for the integral aqueous extraction of citrus peel waste resulting in hesperidin-rich products, either aqueous extracts or pectin tablets. The uptake of this process on a relevant scale is urged, in order to achieve large-scale production and distribution of hesperidin-rich products. Meanwhile, experimental and clinical studies could determine the effective doses either for therapeutic and preventive purposes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic – also known as COronaVIrus Disease 19 (COVID-19) – could have been favored by specific weather conditions. It was found that the 2020 winter weather in the region of Wuhan (Hubei, Central China) – where the virus first broke out in December and spread widely from January to February 2020 – was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic has been very severe from February to March. The similarity suggests that this pandemic worsens under weather temperatures between 4°C and 11°C. Based on this result, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From January to March, this isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, coinciding with the geographic regions most affected by the pandemic from January to March. It is predicted that next spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year. Google-Earth-Pro interactive-maps are provided as supplements.

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

Human-to-animal SARS-CoV-2 transmission was observed, including a veterinarian contracting COVID-19 through close contact with an infected cat, suggesting an atypical anthropozoonotic transmission. This study investigated the prevalence of SARS-CoV-2 antibodies in cats during human outbreaks and elucidated the correlation between cat infections and human epidemics. A total of 1,107 cat sera samples were collected and screened for SARS-CoV-2 antibodies using a modified indirect ELISA human SARS-CoV-2 antibodies detection kit. The samples were confirmed using a cPass surrogate viral neutralization assay. The SARS-CoV-2 seropositivity rate was 22.67% (199/878), mirroring the trend observed in concomitant human case numbers. The waves of an epidemic and provinces did not significantly impact ELISA-positive cat. Notably, Chon Buri ex-hibited a strong positive correlation (r = 0.99, P = 0.009) between positive cat sera and reported human case numbers. Additionally, cPass surrogate viral neutralization revealed a 3.99% (35/878) seropositivity rate. While there were significant differences in positive cat numbers and proportions between epidemic waves. In Samut Sakhon, a positive correlation (r = 1, P = 0.042) was noted between the proportion of positive cat sera and reported human cases. The findings emphasize the need for ongoing surveillance to comprehend SARS-CoV-2 dynamics in both human and feline populations.

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. Background: This study offers an approach on histopathological and immunohistochemical placental observations from SARS-CoV-2 positive mothers compared negative ones. Methods: Out of 44 examined placentas, 24 were collected from patients with SARS-CoV-2 infection during pregnancy and 20 without infection. Results: The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblast and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV), thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%) and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), chorioamnionitis (5%) and two cases of meconium (19%). Our results were consistent with literature. Conclusions: This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p=0.01) and fibrin deposition (p=0.01). Further research is necessary to establish whether SARS-CoV-2 is the cause of vascular pathologies during pregnancy.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

During the COVID-19 pandemic, the circulation of non–SARS-CoV-2 respiratory viruses changed throughout the world. This study aimed to analyze the effect of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (RV), and parainfluenza (PIV)-3 single infection, dual co-infection, and viral load on cytokine and chemokine expression in 300 Mexican patients with ARIs negative for SARS-CoV-2. Molecular detection and viral load were performed by RT-qPCR. Cytokine and chemokine expression was determined in samples positive for single RSV, MPV, RV, or PIV-3 infection, and in the most frequent dual co-infections, by a cytokine panel using a magnetic-bead-based multiplex immunoassay. Of the patients positive for viral infection, 91.7% had a single infection and 8.3% had dual co-infections. In this study, RSV was the respiratory virus with the highest prevalence, and the most common dual co-infection was RV+RSV. On the other hand, RV infections had the highest viral loads compared to the other viruses detected. FGF basic, MIP-1α IL-8, IP-10, MCP-1, IFN-γ, and RANTES showed differential expression between single infections and dual co-infections compared to healthy patients. We report, for the first time, the circulation of non-SARS-CoV-2 viruses in the south of Mexico and the cytokine and chemokine profiles associated with these viruses.

Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode for transmission. In addition to tools like vaccination and testing, counter-measures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model. Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to un-treated air. Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a muti-day exposure period during peak viral shedding from hamsters. Conclusion: These findings demonstrate the efficacy of the UV-C light to mitigate airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool to reduce infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden collected between March 2022 and May 2023 were whole-genome sequenced using next-generation sequencing, mainly with the Nanopore sequencing method. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. The dominant sublineages changed over time and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.