An outbreak of a pandemic COVID-19 disease caused by a novel coronavirus SARS-CoV-2 has posed a serious threat to human health and the economy of the whole world. Bangladesh is one of the most densely populated countries in the world, which has also come under the attack of this viral disease. This perspective report aimed to describe the responses of Bangladesh to tackle the COVID-19, particularly on how Bangladesh is dealing with this novel viral disease with limited resources. The first case of a COVID-19 patient was detected in Bangladesh on March 8, 2020. Since then, a total of 2,144 peoples are officially reported as COVID-19 infected with 84 deaths. To combat the COVID-19, the government has taken various steps to tackle the epidemic outbreak of it such as diagnosis of the suspected cases, quarantine of doubted people and isolation of infected patients, local or regional lockdown, grant general leave from all offices for staying home of people, increase public awareness and enforce social distancing and so on. In addition, to address the socio-economic situations, the government announced several financial stimulus packages of about USD 11.17 billion. However, very limited diagnostic facilities, health workers, resources such as hospital beds, personal protective equipment, intensive care unit, and ventilators in the hospitals along with limited public unawareness are the major challenges for Bangladesh to tackle the situation effectively. This report described the responses of Bangladesh to tackle the COVID-19 and discusses prevailing challenges to mitigate this highly contagious disease with limited resources.

On March 11^th 2020, the World Health Organization (WHO) declared the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV2) as a pandemic. Until an effective treatment or a vaccine is developed, the current recommendations are to contain the disease, and control its transmission. It is now clear that the primary mode of SARS-CoV2 transmission is aerosol/droplet spread, and by contacting virus contaminated surfaces acting as fomites (inanimate vectors). Furthermore, recent data indicate that the live virus particles are present in saliva, and, more alarmingly, asymptomatic individuals may transmit the infection. By virtue of the nature of the practice of dentistry where intrinsically, a high volume of aerosols are produced, as well as the close proximity of dentists and patients during treatment, dentists and allied dental staff are considered the highest risk health professional group for acquiring SARS-CoV2 during patient management. Therefore, several organizations and specialty associations have proposed guidelines and recommendations for limiting the transmission of SARS-COV2 from carriers to dentists and vice versa. This paper aims to provide a review of these guidelines, and concludes with a brief look at how the practice of dentistry may be impacted by COVID-19, in the post-pandemic era.

With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.

In December 2019, outbreak of novel coronavirus (COVID-19) occurred in Wuhan, Hubei Province, China and exported across the world leading to thousands of deaths and millions of suspected cases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection into the host undergoes a huge number of complex replicative machineries which still remains unclear. Understanding the mechanism (s) of replication and mode of infection of SARS-CoV2 to human cells will help us in the development of novel vaccines or drugs for the eradication and prevention of the disease. This review compiles the knowledge of SARS-CoV2 replicative machinery, mode of infection to the human cells and the development of drugs and vaccines which are currently under clinical trials.

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.

Spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) made a historic transition between December 2019 to March 2020. In the present scenario SARS-CoV-2 as becomes a major burden on public health and economic stability of societies around the globe. From the substantial evidences gained from the pandemic of SARS-CoV-2 and MERS-CoV (Middle East respiratory syndrome coronavirus), scientists and clinicians strongly believes that these pathogenic viruses share common homology of some biologically active enzymes which includes RNA-dependent RNA polymerase (RdRP), 3-chymotrypsin-like protease (3CL^pro), papain-like protease (PL^pro) etc. RdRP relatively grabs higher level of clinical importance in comparison with other enzyme target. Indian system of traditional medicine pioneering the therapy towards infectious disease since several centuries. In view of this potential therapeutic leads from some of the Indian medicines along with standard drug favipiravir subjected to docking investigation targeting SARS-CoV-2- RNA dependent RNA polymerase (RdRp). Residual proximity analysis reveals 18 out of 28 compounds reveals potential binding affinity of about 100% with the target amino acid residue (618 ASP, 760 ASP,761 ASP), 7 out of 28 reveals 75% binding efficacy and 3 out of 28 reveals 25% binding efficacy with that of the target residue. Hence further clinical validation may be warranted with proper in-vitro and in-vivo studies prior to the clinical recommendation in treating COVID-19 patient’s.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

Background: Coronavirus disease 2019 (COVID-19) is a new viral respiratory disease and whether pregnant women are at increased risk of infection is unknown. Viral pneumonia is an important indirect cause of maternal death. Little is known about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Objective: To describe the clinical characteristics of COVID-19 in pregnancy and their newborn infant, and we sought to explored whether the SARS-CoV-2 can be intrauterine vertically transmitted. Study Design: The study was a case series study conducted in the obstetric ward of Tongji Hospital affiliated to Huazhong University of science and technology, Wuhan, China. Demographic, clinical, laboratory and radiological profiles of the SARS-CoV-2 infection case series. A systematic testing procedure for SARS-CoV-2 infection using oropharyngeal swab, placenta tissue, vaginal mucus, and breast milk of mothers. and oropharyngeal swab, umbilical cord blood, and serum of newborns was conducted. Results: We have conducted the most thorough virological assessment to date, and we include a longer clinical observation in mother-infant dyads during hospitalization. The clinical course and outcomes of three pregnant women who acquired SARS-CoV-2 infection late pregnancy are described in mother-infant dyads. Two had caesarean delivery in their third trimester. All patients showed an uneventful perinatal course, and a successful outcome. No infants became infected by vertical transmission or during delivery. Conclusion: No evidence to suggest the potential risk of intrauterine vertical transmission in the case series and further in-depth study is needed. Both the pregnancy woman and infant showed fewer adverse maternal and neonatal outcomes.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

G-protein-coupled receptors (GPCR) belong to a large family of molecules eliciting different responses to a variety of signaling molecules. These receptors participate in various physiologic pathways such as metabolism, growth, immune responses, inflammation, vision, taste, olfaction, neurotransmission and even and pathologic responses including chronic inflammatory and vascular diseases. Receptors contributing to the biological responses of renin-angiotensin system (RAS) are members of GPCR family. COVID-19-induced inflammatory cascade has been attributed to acute ACE2 downregulation and imbalance of proinflammatory ACE/AngII/AT1R and anti-inflammatory ACE2/angiotensin (1-7)/Mas axes in favor of the former. Some of the receptors contributing to activities of proteins in RAS including AT1R, AT2R and Mas receptors are members of GPCR family. It is notable that these receptors induce their effects both through G protein and β-arrestin pathway; the former exerts temporary and the latter more sustained effects. In addition to the imbalance of GPCR responses contributing to RAS activities, it has been suggested that SARS-CoV2 pathogenesis might be attributed to the activation of GPCRs or modulating G-proteins involved in adenosine-CFTR regulation system and epithelial Na channel function.This article includes a minireview about the physiological functions of GPCRs and their contribution to COVID-19.

Beginning in December 2019, a novel coronavirus known as SARS-CoV-2 has caused an international outbreak of respiratory illness termed COVID-19. This disease may cause mild to moderate respiratory illness. However, older individuals and those with underlying medical conditions like diabetes, cancer, and cardiovascular disease are more likely to develop serious illnesses (progressive pneumonia, multi-organ failure, and even death) (1). The main target for antiviral therapy for COVID-19 is the 3CL protease (3CLpro, Main protease, Mpro, Nsp5). The 3CL protease plays an integral role in viral replication and is often known as the “Achilles heel” of the SARS-CoV-2 virus (2). Thus, NLC Pharma utilized a unique and novel technology termed Quantum Core Technology (QCT) to design a mechanism-based potent inhibitor against the SARS-Cov-2 3CL protease. 3CL Pharma has designed an oral anti-viral for COVID-19 called Tollovir. Biochemical assays have revealed that 40uM of Tollovir in PBS can achieve 90% maximum inhibition of 3CL protease. Furthermore, the oral anti-viral has completed clinical trial phase 2b/3. Tollovir has proven to be safe and significantly decreases mortality rates of hospitalized patients with COVID-19 infection.

Isolation, quarantine, and contact tracing were some of the most critical and commonly employed non-pharmaceutical interventions to control the COVID-19 pandemic. However, the effectiveness of these strategies after their implementation depends upon many factors such as the country's population, availability of sufficient resources to diagnose and effectively isolate the infected individuals, and feasibility, and acceptability of isolation and quarantine policy by the public. This narrative review aims to appraise the current evidence on the correct implementation strategies and shortcomings made in the isolation and quarantine strategies during the COVID-19 pandemic. PubMed, SCOPUS, EMBASE, and Web of Science citation index with the following keywords were searched: Pandemic, COVID-19, Coronavirus, Quarantine, and Isolation. The results showed that quarantine and isolation of COVID-19 patients were more effective than late adoption (5-fold versus 2.6-fold)’. Around 90% of outbreaks could have been managed if 80% of contacts were monitored, traced, and isolated within 4 days. For each new case of COVID-19, around thirty-six individuals should have been traced. When the percentage of individuals without symptoms is greater than 30%, isolation and contact tracing alone cannot contain the infection. The delay between the onset of symptoms and isolation is the most important factor determining whether an outbreak is controllable. The ideal day for testing should start on the 6th of the quarantine. However, this evidence is mostly based on mathematical modeling studies, and evidence for its effectiveness in real scenarios is required. Symptom-based isolation strategy should not be considered the sole criterion for considering isolation.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

To discover potential micro(mi)RNAs biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. A totally of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow.

Severe acute respiratory syndrome coronavirus 2 infects many people, but many infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus, and it is associated with liver injury and other complications leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for treatment of hospitalized patients with COVID-19 to improve time to recovery, reduce duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than 5 times the upper limit of normal in hospitalized patients with COVID-19 but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir and that a 5-day course of remdesivir seems to be safe in regards to hepatotoxicity.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

Abstract: The COVID-19 pandemic significantly disrupted global healthcare systems. The impacts of SARS-CoV-2 infection on urticaria and its management are unknown. To collect information about patients with urticaria infected with SARS-CoV-2 and to investigate the impact of SARS-CoV-2 infection on urticaria severity, course, and treatment to better support recovery. This was a questionnaire-based study of patients with urticaria infected with SARS-CoV-2. Changes in urticaria severity (measured with the urticaria activity score (UAS)), course, and treatment were assessed before, during, and after SARS-CoV-2 infection. Mean (± SD) UAS scores were 5.17 ± 1.67, 4.23 ± 1.98, and 4.37 ± 1.93 before, during, and after SARS-CoV-2 infection, respectively (F = 8.839, p < 0.01). The median (IQR) wheal score was 0.464 (0.464, 0.763), 0.464 (0.138, 0.763), and 0.464 (0.138, 0.763) before, during, and after infection, respectively (Kruskal-Wallis H-test, H=12.230, p = 0.02). The median (IQR) pruritus score was 0.695 (0.395, 0.695), 0.394 (0.123, 0.695), and 0.394 (0.123, 0.695) before, during, and after infection, respectively (Kruskal-Wallis H-test, H = 21.001, p < 0.01). Within the limitations of a questionnaire study, urticaria appears to improve during SARS-CoV-2 infection, worsens slightly after recovery, and the frequency of Western medicine use increases.

Objectives: The aim of our study was to evaluate patients after suicide attempts treated at the Department of Trauma Surgery for Children before and after the outbreak of the Covid-19 pandemic. Material and methods: Retrospective review of the medical database at equal time intervals of 24 months to identify patients treated before and after the COVID-19 was done. Thorough analysis including injury mechanism, medical procedures, history of previous mental disorders or suicidal behavior was performed. Furthermore, results were compared with the Polish police suicide statistics. Results: Based on our retrospective review we found 4 patients treated in our department before the pandemic and 10 patients treated after COVID-19 outbreak. The group before SARS-Cov-2 era consisted of three girls and one boy with a mean age of 14.97 (12.7-17.6). The group treated in the pandemic crisis consisted of 8 boys and 2 girls, the mean age was 15.49 (10.8-17.2). In the pre-COVID-19 group, 2 out of 4 patients had received psychiatric treatment before, but none had attempted suicide before. In the COVID-19 group, 6 out of 10 patients had previously received psychiatric treatment, moreover 3 of them attempted suicide before. Based on our analysis, the number of individuals who displayed suicidal attempts has raised. Between 2018 and 2021 the largest number of suicides concerned the 13-18 y.o. group, both for the Silesian Voivodeship (H=9.374; p=0.0092) and for the whole country (H= 10.203; p=0.0061). Conclusions: 1. Results of our study indicate that the pandemic may have caused a wide range of negative mental health consequences for young individuals; 2. During the SARS-Cov-2 era, we observed an alarming 2.5-fold increase in the number of patients treated after suicide attempts at the children's orthopedic trauma department; 3. Suicide attempts in children are often related with high energy trauma.

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all the cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays of PBMC. We included 5 nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT to at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

We introduce a magnetic bead-based sample preparation scheme for enabling a Raman spectroscopic differentiation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positive and negative samples. The beads were functionalized with the angiotensin-converting enzyme 2 (ACE2) receptor protein, which is used as recognition element to selectively enrich SARS-CoV-2 on the surface of the magnetic beads. Subsequent Raman measurements directly enable discriminating SARS-CoV-2 positive and negative samples. The proposed approach is applicable for other virus species, too, when the specific recognition element is exchanged. Series of Raman spectra were measured on three types of samples, namely SARS-CoV-2, Influenza A H1N1 virus and a negative control. For each sample type, eight independent replicates were considered. All spectra are dominated by the magnetic bead substrate and no obvious differences between sample types are apparent. In order to address the subtle differences in the spectra, we calculated different correlation coefficients, namely the Pearson coefficient and the Normalized Cross Correlation coefficient. By comparing the correlation with the negative control differentiating between SARS-CoV-2 and Influenza A virus is possible. This study provides a first step towards the detection and potential classification of different viruses with the use of conventional Raman spectroscopy.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. During September 28, 2021 to April 11, 2022, we conducted a cross-sectional survey of community members adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥12 years, 127 (55%) received >1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥12 years old unvaccinated (n=106) were more likely to be female (73% vs 41%, p<0.001) and homemakers (69% vs 24%, p<0.01) compared with vaccinated participants (n=127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. By our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD) is a pervasive public health concern, intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and metabolic dysfunction-associated fatty liver disease (MAFLD) is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among metabolic dysfunction-associated fatty liver disease (MAFLD) patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.

Acute appendicitis is the most common surgical emergency worldwide with peak incidence in the age range of 10 – 19 years, and the standard treatment procedure is the surgical removal of the appendix to avoid complications such as its rupture, peritonitis, and sepsis. The COVID-19 pandemic required the global population to stay indoors to stop the spread of virus, which led to a decline in the number of patients visiting the hospital for non- COVID -19 related emergencies. This is a case of a 9-year-old girl who tested positive for COVID -19 and developed acute appendicitis and benefited from individualised classical homeopathy. Further scientific investigation is necessary to establish the relevance of individualised classical homeopathy in treating serious acute conditions such as acute appendicitis.

Since the beginning of 2020, tetracycline (TC), such as minocycline (MINO), has been used to inhibit coronavirus disease 2019 (COVID-19). Traditional Japanese Kampo medicine, such as Saiko-keishi-to (SKT), has recently received a lot of attention for its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects. We describe a COVID-19 patient treated with MINO and SKT in anticipation of their anti-SARS-CoV-2 properties. A 90-year-old male patient with Alzheimer’s disease was referred to a medical clinic due to fever, appetite loss, and general malaise. Based on positive SARS-CoV-2 rapid antigen tests, he was diagnosed with COVID-19. He did not have COVID-19 pneumonia, but he had difficulty in eating on his own. As a result, he was referred to a hospital for admission. After admission, he was treated with molnupiravir to avoid aggravation. Seven days after his admission, he was discharged. After his discharge, he was referred to our hospital as an outpatient due to a prolonged mild fever and general malaise. As a precaution, a real-time reverse transcription-polymerase chain reaction (RT-PCR) test was performed, which yielded a positive result. Therefore, the aforementioned symptoms were thought to be caused by prolonged COVID-19. He was treated with MINO and SKT due to the anti-viral properties of these two drugs. The RT-PCR test became negative 7 days after receiving this treatment, and the fever and general malaise subsided.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths to date worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence as well as immune and vaccine escape capabilities highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to get infected by the virus, more likely to develop severe disease and exhibit higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and in particular androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2 as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection and antiandrogens could be used as a preventative measure at the pre- or early-hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.

Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.

Matrix metalloproteinases are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are involved in the inflammatory response by regulating the activities of TNF-alpha and IL-1beta, which are pro-inflammatory cytokines, in addition to extracellular matrix components. Since the regulation of inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases, many studies have been conducted on the role of MMPs in pathogenesis. In addition, various studies have demonstrated that MMPs are involved in the pathogenesis of infectious diseases by regulating the expression and activity of MMPs by infection with pathogens. In this review, we discuss the role of MMPs in infectious diseases and the role of MMPs in inflammatory responses and present their potential as therapeutic targets in infectious diseases.

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.

The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.

To determine the ethical-attitudinal profile of university students in the education career during the pandemic with a tendency towards a new normality. University students of the education career were surveyed online, in an ethical key (axiological attitude, moral attitude and attitude towards new normality). The research was descriptive of univariate hypothesis, with non-probabilistic snowball sampling, reaching a sample of 480 participants. The Ethical-Attitudinal Profile Scale (EPEA) was designed, whose reliability was 0.93 in Lawshe's formula and 0.89 in Cronbach's Alpha. In the axiological attitude, values were obtained more frequently: respect with 79%, sincerity with 73%, prudence with 72%. In the moral attitude, a polar result is contrasted between laxity (67%) and kindness (45%); while, in the attitude towards new normality, there was no spike in frequencies, being distributed more homogeneously between indicators, with a low resilience index. There is an adequate evaluative profile of the university students of the education career despite the context of the pandemic and the trend towards a new normality; having a moral attitude of laxity inferred by the circumstances of uncertainty that are experienced in adverse contexts.

Following the WHO's declaration of a public health emergency due to the COVID-19 outbreak, the subsequent quarantine and confinement measures that were adopted, including distance learning measures, were shown to have caused a significant deterioration in the mental health of medical students. The goal of this study was to explore the mediating role of resilience and life satisfac-tion in the relationship between perceived stress and burnout among medical students in the con-text of COVID-19. A transversal assessment was performed using an online questionnaire, to which 462 students responded. The instruments applied were the Perceived Stress Scale-10, the Resilience Scale-25 items, the Satisfaction with Life Scale (SWLS) and the Burnout Scale (Olden-burg Inventory). A regression model was estimated for each dimension of burnout. The results revealed that resilience and life satisfaction play a mediating role in the association between stress and the dimensions of burnout. This suggests that measures of promoting mental health based on resilience and improving perceptions of life should be implemented.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.

There is a relatively high risk of virus transmission in dental procedures and oropharyngeal examinations. We investigated the effects of mouthwashes on covid-19 viral load reduction during dental practices and oro-pharyngeal assessments. We performed a systematic search in PubMed, EMBASE, Scopus, Web of Science, Cochrane library for relevant studies up to February 2021. Papers evaluating patients with covid-19 infection (patients) who rinse mouthwashes (intervention) compared to patients who don’t rinse them (comparison) for reducing covid-19 viral load or reducing cross-infection of covid-19 (outcome) in the randomized and non-randomized clinical trial and quasi-experimental studies (study) were included due to PICOS question. Three independent authors conducted literature screening and data extraction. We extracted the most relevant data and we evaluated the risk of bias from the included studies. Out of 344 potentially eligible articles, six studies were included in this systematic review. Regarding viral load and negative cycle threshold (ct) values, 1% PVP_I and Listerine mouthwash were effective. 0.12% CHX mouthwash was effective 0-2 hours post rinsing, but it was not effective after 2 hours. A mixture solution of 0.2% Chlorhexidine gluconate and 6% Hydrogen peroxide was effective on day 5 of intervention. Gargling 1% hydrogen peroxide, 0.075% Cetylpiridinum Chloride (CPC), 0.5%PVP-I and 0.2% CHX mouthwashes was not effective on SARS-COV-2. It cannot be guaranteed that rinsing a specific kind of mouthwash prevents cross-infection of covid-19; however, the viral load of SARS-COV-2 in saliva will be decreased after rinsing mouthwashes containing 1%PVP-I and Listerine.

A global event such as the COVID-19 crisis presents new, often unexpected responses that are fascinating to investigate from both, scientific and social standpoints. Despite several documented similarities, the Coronavirus pandemic is clearly distinct from the 1918 flu pandemic in terms of our exponentially increased, almost instantaneous ability to access/share information, offering an unprecedented opportunity to visualise rippling effects of global events across space and time. Personal devices provide “big data” on people’s movement, the environment and economic trends, while access to the unprecedented flurry in scientific publications and media posts provides a measure of the response of the educated world to the crisis. Most bibliometric (co-authorship, co-citation, or bibliographic coupling) analyses ignore the time dimension, but COVID-19 has made it possible to perform a detailed temporal investigation into the pandemic. Here, we report a comprehensive network analysis based on more than 20000 published documents on viral epidemics, authored by over 75,000 individuals from 140 nations in the past one year of the crisis. In contrast to the 1918 flu pandemic, access to published data over the past two decades enabled a comparison of publishing trends between the ongoing COVID-19 pandemic and those of the 2003 SARS epidemic, to study changes in thematic foci and societal pressures dictating research over the course of a crisis.

Background: CoronaVirus Disease 2019 (COVID-19) is the main discussed topic world-wide in 2020 and at the beginning of the Italian epidemic, scientists tried to understand the virus diffusion and the epidemic curve of positive cases with controversial findings and numbers. Objectives: In this paper, a data analytics study on the diffusion of COVID-19 in Lombardy Region and Campania Region is developed in order to identify the driver that sparked the second wave in Italy Methods: Starting from all the available official data collected about the diffusion of COVID-19, we analyzed google mobility data, school data and infection data for two big regions in Italy: Lombardy Region and Campania Region, which adopted two different approaches in opening and closing schools. To reinforce our findings, we also extended the analysis to the Emilia Romagna Region. Results: The paper aims at showing how different policies adopted in school opening / closing may have on the impact on the COVID-19 spread. Conclusions: The paper shows that a clear correlation exists between the school contagion and the subsequent temporal overall contagion in a geographical area.

CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

Based on comprehensible non-parametric methods, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented. Where appropriate, the estimates for Germany are compared with the results for seven other countries (FR, IT, US, UK, ES, CH, BR) to get an idea of the breadth of applicability and a relational understanding. Thereby, only prevalence data of daily reported new counts of diagnosed cases and fatalities provided by the Johns Hopkins University are used. Drawing on uncertain a priori knowledge is avoided. Specifically, we present estimates resulting from delay-time correlations for the duration from diagnosis to death being 13 days for Germany and Switzerland. The delay-time correlation applied to time series from other countries exhibit less pronounced peaks suggesting high variabilities for the corresponding time-to-death durations. With respect to the German data, the two time series of new cases and fatalities exhibit a strong coherence within the frequency range of interest, which backs our findings. Furthermore, based on the knowledge of this time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality-case ratios are calculated having superiority compared to the commonly published case-fatality rate. The temporal median of the instantaneous fatality-case ratio with proper delay of 13-days between cases and deaths for Germany turns out to be 0.02. Time courses of asymptotic fatality-case ratios are presented for other countries which substantially differ during the first half of the pandemic, however, converge to a narrow range with standard deviation 0.57% and mean 2.4%. Additionally, the time courses of instantaneous fatality-case ratios with optimal delay for the 8 exemplarily chosen countries are calculated and compared by means of the temporal medians. Similarly to the asymptotic fatality-case ratios, the differences are much smaller than expected from mass media reports. The basic reproduction number, R₀, for Germany is estimated to be between 2.4 and 3.4. The uncertainty stems from uncertain knowledge of the generation time. A delay autocorrelation shows resonances at about 4 days and 7 days, where the latter resonance is at least partially attributable to the sampling process with weekly periodicity. The calculation of the basic reproduction number is based on an evaluation of cumulative numbers of cases yielding time-dependent doubling times as an intermediate step. This allows to infer to the reproduction number during the early phase of onset of the epidemic. In a second approach, the instantaneous reproduction number is derived from the incident (counts of new) cases and allows, in contrast to the first version, to infer to the temporal behaviour of the reproduction number during the later epidemic course. The time course of the reproduction number is compared to an alternative control measure given by the per capita growth, which largely confirms the conclusions drawn from the reproduction number. To conclude, by avoiding complicated parametric models we provide insights into basic features of the COVID-19 epidemic in an utmost transparent and comprehensible way. The perhaps most striking insight is that the fatality-case ratios do not differ between countries as much as previously suspected.

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective is to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1, 48 h or continuously with 10-7 M Nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-beta-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca+2, ATP and EMT were evaluated by ELISA and/or western blotting. (3) Results: Nicotine induced through α7-nAChR (i) increase in cell viability (ii) cell proliferation; (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation (v) EGFR/pEGFR over-expression; (vi) increase in basal Ca+2 concentration, (vii) reduction of ATP production; (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that Nicotine potentiates viral infection it is likely that Nicotine is involved in SARS-CoV-2 infection and severity

Historically, 2020 will be remembered as the year of COVID-19 pandemic, that limited people move and their social habits. This virus, becomes the first daily tracked public health burden that leads to more than 1,2 million deaths in the World by the end of October 2020, and until now no countries' best control strategies are cited as the example of long term success.Since March 2^nd, 2020, date of the first SARS-COV-2 detected case in Morocco; many decisions were adopted as COVID-19 control strategies. If the first period of COVID-19 noticed a few numbers of cases and deaths, the second half from July is marked with an exponential increase of the number of cases and a spread in almost all provinces with more intensive care needs and more deaths. The policy analysis approach was followed as a method to define the pitfalls themes and to compare with the updated available international information any significant similarities or divergences. Thus, this report has the aim to present an overview of how the COVID-19 pandemic was dealt in Morocco during these 200 days, by highlighting some discrepancies with corrective advice provided in the first version of the manuscript to be confronted by a Moroccan health policymaker’s community, then to notice the decisions adopted during another one month by the MoH to get better future control results against COVID-19.Unfortunately, despite the MoH decision to increase the diagnostic facilities for molecular tests, the overall number of laboratory tests do not go further than 21000 tests per day. The actual insidious transmission is a dangerous blind threat that dissipates the collaborating efforts, due to this limited number of confirmation and follows up tests.Accurate, standardised and up to ten times per day tests of molecular biology represented by RT-qPCR, to interpret results following the time progress of cycle quantification values is the primary action to be done to enhance the overall control strategy.

Increased demand for wearing face masks, lack of surgical masks and N95 respirators during the coronavirus pandemic created alternative needs for cloth masks. Therefore, to determine filtration efficacy, reusability and duration of wearing new and hand washed cloth masks, the bacteria filtration efficacy was tested using Staphylococcus aureus and Escherichia coli. Cotton cloth masks; single layer without pleats and with pleats, double layer with canvas filter in the middle, double layer with stiff filter in the middle, double layer with pleats on both sides and locally made and imported surgical masks and N95 respirators were used. Bacterial suspension was sprayed over outer surface and swabbed from inner surface at 0hrs, 4thhr, 8thhr and 12thhr. Similar procedure was performed to hand washed and ironed cotton cloth masks. After 24 hours of incubation, single layer without pleats and with pleats had no filtration efficacy(0-100%). Double layer with stiff filter in the middle and double layer with pleats on both sides had higher filtration efficacy(99.96-100%), this filtration efficacy remained up to three occasions of hand washing with soap and water, conferring protection up to 12hours. Filtration efficacy of surgical masks made locally, imported and N95 respirators were 90-100%, 99.99-100%, and 99.99-100% respectively.

Taking advantage of tourists’ intensive flow, the SARS-CoV-2 virus rapidly spread causing thousands of deaths globally. Trying to contain the already pandemic virus, government travel restrictions were suddenly imposed. Consequently, the tourism industry, which at that moment employed one in ten workers globally, suddenly collapsed. Hundreds of thousands of workers immediately lost their income. Flights were cancelled, and thousands of tourists were stuck abroad with no means to return to their home countries. The gravity of the situation raised the question of whether there was scholarly knowledge that could have helped manage tourism during the current pandemic. To answer this question, a methodical literature review was performed, allowing for up to 900 publications to be analysed. Keywords used were pandemic, tourism, tourist and travel. Based on this process, 63 publications were selected for further analysis. Among these, less than 5% were focused on the tourism side of the problem. As such, this research concludes that, by the time the novel coronavirus emerged, there was, virtually, no scholarly knowledge on how to manage tourism during pandemic times so as to avoid chaos, and that the scholarly community studying related issues is very small. Moving forward, this article recommends that research funding agencies and universities encourage the sound development of this area of knowledge. Aspects that should be investigated include when, how and by whom should tourism be halted, as well as the feasibility of a Tourism World Fund for supporting related costs.

Human civilizations are under enormous threats due to the outbreak of novel coronavirus (COVID-19) originated from Wuhan, China. The asymptomatic carriers are the potential spreads of this novel virus. Since, guaranteed antiviral treatments have not been available in the market so far, it is really challenging to fight against this contagious disease. To save the living mankind, it is urgent to know more about how the virus transmits itself from one to another quite rapidly and how we can predict future infections. Scientists and Researchers are working hard in investigating to understand its high infection rate and transmission process. One possible way to know is to use our existing COVID-19 infection data and prepare a useful model to predict the future trend. Mathematical modelling is very useful to understand the basic principle of COVID-19 transmission and provide necessary guidelines for future prediction. Here, we have reviewed 9 distinct commonly used models based on Mathematical implementations for COVID-19 transmission and dig into the deep head to head comparison of each model. Finally, we have discussed interesting key behaviour of each model, relevant upcoming important issues, challenges and future directions.

Abstract The COVID-19 pandemic has tremendously affected the African continent and the rest of the world. Most businesses have closed and a lot of people have lost their jobs. The aviation industry has been shaken to the core with airlines losing millions of dollars and flights being cancelled. The tourism industry has consequently been affected due to restricted travel of tourists, impacting wildlife conservation and livelihoods. Schools, colleges and universities have been closed. The virus has infected millions of people and hundreds of thousands of people have died globally putting strain on health systems especially those of hard hit countries. Various countries all over the world have put measures to control the spread of the virus through lockdowns and social distancing policies. The reduced economic activities and mobility of people has resulted in improved air quality, cleaner water and beaches in some countries. However there are also negative impacts such as challenges in waste management, increased pharmaceutical and household waste and discovery of the corona virus in wastewater, a potential threat to public health. A considerable amount of research has been done on the socio-economic impacts of COVID-19 in Africa but there is still limited research on its impact on the environment. This paper serves to highlight the observed and potential environmental impacts of COVID-19 in Africa.

Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

The rapidly evolving understanding of Coronavirus Disease 2019 (COVID-19) respiratory failure pathogenesis, limited disease-specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. In this single-centre retrospective cohort study we describe the outcomes of COVID-19 patients admitted to Guy’s and St. Thomas’ NHS Foundation Trust (GSTT) critical care service. Patients were managed according to a local respiratory failure management pathway that was predicated on timely invasive ventilation when indicated and tailored ventilatory strategies according to pulmonary mechanics. Between 2nd March and 25th May 2020 GSTT critical care service admitted 316 patients with confirmed COVID-19. Of the 201 patients admitted directly through the Emergency Department with a completed critical care outcome, 71.1% survived to critical care discharge. These favourable outcomes may serve to inform the wider debate on the optimal ventilatory management in COVID-19.

Herd immunity happens when a relatively large proportion of a population becomes infected by an agent, subsequently recovers, and attains immunity against the same agent. That proportion thus indirectly protects the naïve population by preventing the spread of the infection. Herd immunity has been suggested to interrupt and control the COVID-19 pandemic. However, relying on establishing herd immunity can be catastrophic considering the virulence and lethality of SARS-CoV-2. Meanwhile our understanding of the pathogenesis, case-fatality rate, transmission routes, and antiviral therapy for COVID-19 remains limited now. Interrupting or slowing the COVID-19 transmission seems more opportune than vaccination, antiviral therapy, or herd immunity, all of which will take some time to yield. Thus, social distancing, face-masking, and hygiene are the most appropriate immediate countermeasures. Because the social fabrics, economic implications, and local demands of various nations are unique, early relaxation of restrictions may seem hasty particularly when fatality rates are high, or when the healthcare systems could be inadequate or become inundated. Conclusively, avoiding any overwhelmingly risky approach in fighting the pandemic is prudent.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

COVID-19 is a pandemic with no cure. There is an urgent need for low-cost interventions. Macroclimate work through affecting microclimate. In many situations, man-made microclimate, such as air conditioning, may override the effect of natural macroclimate in determining SARS-CoV-2 pathogenicity. Ambient temperature (AT) has been roughly associated to SARS-CoV-2 transmission. To translate into a feasible practice in controlling COVID-19 pandemic, in-depth and implementable knowledge of AT role in SARS-CoV-2 transmission should be unveiled. This study aimed to determine if there is a ‘safe’ temperature that is comfortable to human beings while significantly inhibitory for SARS-CoV-2 pathogenicity. Data on monthly new deaths or new cases per million population (MDPM or MCPM) and monthly cumulated days with more cases than the previous day (DI) from March 2 to June 30, 2020 were collected from all 118 countries with population over five million. Monthly average AT negatively correlated with the transmission parameters. A significant decrease in transmission was observed when AT reached above 20 ºC. Monthly average (not average high) AT of countries with MDPM <2, MCPM<10, or DI<=7 was found to be between 24.54 and 26.89 ºC (25.18 ºC on average) with average standard error of 4.81. Thus, average AT <20, 20-25, >25 ºC were considered as high, medium, and low risk AT. Furthermore, MDPM in countries with AT <20 ºC were 80.93, 50.23, 13.52, and 5.05 times of those in countries with AT >25 ºC in March, April, May, and June, respectively. MDPM low-risk rates (<2) in countries with AT >25 ºC were 100, 83.33, 52.73, and 52.46%, respectively. In countries with AT <20 ºC, the trends were opposite. Setting indoor temperature to 25 ºC could decrease the need of social distancing for containing SARS-CoV-2 transmission. Ventilation and sanitizing the air with ultraviolet light in nonbusiness hours may be additionally effective. Cooling indoor temperature too low may be a reason of COVID-19 outbreak in some high AT countries. Authorities and the general population can evaluate COVID-19 risk level and manipulate microclimate to reduce the risk anywhere anytime based on local day average AT.

Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-67; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

The main manifestation of new coronavirus disease 2019 (COVID-19) is respiratory disease. The new coronavirus (SARS-CoV-2) attacks the lungs and may result in severe acute respiratory syndrome. In such cases, the infected person has difficulty breathing, which impairs oxygen uptake in the body. If pneumonia or another respiratory illness develops, and the host immune system is unable to combat SARS-CoV-2, the infected person may eventually die. Meanwhile, reports on unexpected symptoms in organs other than the nasal cavity, throat, and lungs are emerging. To elucidate the causes of such symptoms, we analyzed the expression status of angiotensin-converting enzyme 2 (ACE2), the host receptor used by SARS-CoV-2, in various tissues. This study confirmed that alveolar macrophages appear to be involved in pneumonitis and thrombus formation. In this report, we introduce some new symptoms.

The emergence of novel coronavirus (SARS-CoV-2) in marked as the highest pathogenic coronavirus that has crossed from the hosts to the human population in the twenty-first century. The spreading of COVID-19 in different chinese cities and around the world is travel-related viral spread with the unprecedented nosocomial outbreaks. It has also shown with high case-fatality rates, indeed to urgent prophylactic and therapeutic settings. Scientific advancements of the SARS-CoV-2 pandemic allowed for rapid progress to understand the epidemiology and pathogenesis of SARS-CoV-2. This review highlights the the genomic structure of SARS-CoV-2 with the proposed roles of genotype and phenotype of SARS-CoV-2 in pathogenesis and discuss recent results supporting treatment strategies of COVID-19 with a special focus on how these new insights may facilitate rational development of SARS-CoV-2 for targeted therapies in the future.

A novel coronavirus (2019-nCoV) responsible for a severe acute respiratory disorder (SARS-CoV-2) in humans, with its epicentre in Wuhan, China emerged in December 2019. This coronavirus, by far, has hit >200 countries, affecting 7 million worldwide accounting 11% death of the affected population. The transmission is majorly caused by human-to-human contact and, through fomite. In view of the increasing number of COVID-19 cases and the absence of definitive treatment or vaccinations, WHO has deemed the viral infection a pandemic of international concern. In such grave situations, there is a need for expanding the health sector workforce, government and police workforce, sanitation and prevention strategies. The current article describes the virology aspect, control of COVID-19 and revisits the various treatment options available at present this deadly infection. Epidemiology of COVID-19 is also discussed to further understand the pandemic status of India. The article also discusses implicating quarantine or social distancing, and in extreme cases, lockdown or alternative approaches such as herd or indirect immunity, as a measure to control the pandemic. Lockdown or social distancing will give rise to economic, emotional, political and social downfall in the country. It is estimated that a lockdown period will set back the country, possibly, by $240 billion, yet it stands unavoidable in the spread of control of infection. Thus, policymakers should strategize economic revival depending upon the best possible data and critical understanding.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affects the respiratory system with some patients rapidly progressing to acute respiratory distress syndrome (ARDS). The most common symptoms of the patients are fever, cough, dyspnea, myalgia, and fatigue. Nasopharyngeal and oropharyngeal swab specimens tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) are the most commonly used methods to diagnose COVID-19. Herein, we investigate and discuss a young case of COVID-19, without any pre-existing medical conditions, whose both nasopharyngeal and oropharyngeal swab tests of SARS-CoV-2 were negative in the prodromal phase. However, after three days, with severe dyspnea and rapidly progressed acute respiratory distress syndrome (ARDS), the case was identified as infected by COVID-19 by testing bronchoalveolar lavage fluid (BALF). The patient was intubated in the intensive care unit (ICU) but expired on the fourth day. This case shows the importance of active and accurate monitoring of the patients showing COVID-19 symptoms. Although the BALF test has a higher exposure risk, it is considered more accurate and recommended if performed by an expert operator.

The biosynthesis of DNA inherently competes with RNA synthesis because it depends on the reduction of ribonucleotides (RNA precursors) to 2’-deoxyribonucleotides by ribonucleotide reductase (RNR). Hence, RNA viruses can increase viral RNA production in cells by partially blocking the synthesis of DNA, e.g. by downregulating the mammalian selenoprotein thioredoxin reductase (TR), which normally acts to sustain DNA synthesis by regenerating reduced thioredoxin, a hydrogen donor for RNR. Computational and preliminary experimental evidence supports the hypothesis that a number of pathogenic RNA viruses, including HIV-1, Ebola, Zika, some flu viruses, and SARS-CoV-2, target TR isoforms by antisense. TR knockdown would create a host antioxidant defect that could be partially rectified by increased selenium intake, or be exacerbated by selenium deficiency, contributing to viral pathogenesis. There are several non-selenium-dependent means that viruses might also exploit to slow DNA synthesis, such as targeting RNR itself, or components of the glutaredoxin system, which serves as a backup redox system for RNR. HIV-1 substantially downregulates glutathione synthesis, so it interferes with both the thioredoxin and glutaredoxin systems. Computational results suggest that, like Ebola, SARS-CoV-2 targets TR3 by antisense. TR3 is the only TR isoform that includes an N-terminal glutaredoxin domain, so antisense knockdown of TR3 may also affect both redox systems, favoring RNA synthesis. In contrast, some DNA viruses encode their own glutaredoxins, thioredoxin-like proteins and even RNR homologues – so they are doing just the opposite, favoring DNA synthesis. This is clear evidence that viruses can benefit from shifting the RNA:DNA balance to their advantage.

Emerging highly pathogenic human coronaviruses (CoVs) represent a serious ongoing threat to the public health worldwide. The spike (S) proteins of CoVs are surface glycoproteins that facilitate viral entry into host cells via attachment to their respective cellular receptors. The S protein is believed to be a major immunogenic component of CoVs and a target for neutralizing antibodies (nAbs) and most candidate vaccines. Development of a safe and convenient assay is thus urgently needed to determine the prevalence of CoVs nAbs in the population, to study immune response in infected individuals, and to aid in vaccines and viral entry inhibitors evaluation. While live virus-based neutralization assays are used as gold standard serological methods to detect and measure nAbs, handling of highly pathogenic live CoVs requires strict bio-containment conditions in biosafety level-3 laboratories. On the other hand, use of replication-incompetent pseudoviruses bearing CoVs S proteins could represent a safe and useful method to detect nAbs in serum samples under biosafety level-2 conditions. Here, we describe a detailed protocol of a safe and convenient assay to generate vesicular stomatitis virus (VSV)-based pseudoviruses to evaluate and measure nAbs against highly pathogenic CoVs. The protocol covers methods to produce VSV pseudovirus bearing the S protein of the Middle East respiratory syndrome-CoV (MERS-CoV) and the severe acute respiratory syndrome-CoV-2 (SARS-CoV-2), pseudovirus titration, and pseudovirus neutralizing assay. Such assay could be adapted by different laboratories and researchers working on highly pathogenic CoVs without the need to handle live viruses in biosafety level-3 environment.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

In the end of April nearly 100 cases of children aged between 6 month and 9 years with Kawasaki like disease were reported (mostly in Europe) probably linked to COVID-19. With the increasing awareness of this condition the number of cases reported is increasing worldwide. We aim to sum up the known data about this new entity based on published data (in a case report, a series of 8 cases and in newspapers and society statement) and using our knowledge of classical Kawasaki disease. It seems to be a post infectious disease with an onset between 2-4 weeks after the infection, probably in genetically predisposed children aged between 6 month to 17 years. A very rough estimation of incidence based on current data from Bergamo, Italy, and New York State and a lot assumption is between 0.016% (95% CI:0.013-0.02%) - 0.31% (95% CI: 0.2-0.47%) of infected children. Clinical signs overlaps with Kawasaki disease in some children, but another feature is prominent gastrointestinal manifestations. For the 9 detailed patients most had incomplete presentation for Kawasaki disease (with a mean 1.7 (+/-1.2) criteria per patient for the 5 non fever criterion) and only one had a classical form. In some cases, presentation is closer to toxic shock syndrome or isolated myocarditis. Persistent fever seems to be constant and biological exploration are consistent with inflammation (elevated CRP, ferritin and D-Dimers). Management is described as supportive and children seem to improve rapidly, but can require cardiac or respiratory support. In date of 11 may 2020 there is 4 deaths confirmed linked to these new entities (1 in UK and 3 in New York). Paediatricians and general practitioners need to be aware of these possible evolution following COVID-19 infection. However it seems to be rare and children are probably still spared from most morbidities and mortality linked to COVID-19 infection .There are need of published detailed cohorts to better delineate these entities.

We hypothesize that the reason severe COVID-19 is closely linked to a limited number of conditions such as obesity, hypertension, older age and diabetes is that these conditions are characterized by a pro-inflammatory state in general and an angiotensin converting enzyme-1-bias in particular. We review recent evidence that this pro-inflammatory state can be reversed via regular exercise and a healthy diet. Studies are suggested that could test this hypothesis.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

A novel coronavirus COVID-19 was first emerged in Wuhan city of Hubei Province in China in December 2019. The COVID-19, since then spreads to 213 countries and territories, and has become a pandemic. Genomic analyses have indicated that the virus, popularly named as corona, originated through a natural process and is probably not a purposefully manipulated laboratory construct. However, currently available data are not sufficient to precisely conclude the origin of this fearsome virus. Genome-wide annotation of thousands of genomes revealed that more than 1,407 nucleotide mutations and 722 amino acids replacements occurred at different positions of the SARS-CoV-2. The spike (S) glycoprotein of SARS-CoV-2 possesses a functional polybasic (furin) cleavage site at the S1-S2 boundary through the insertion of 12 nucleotides. It leads to the predicted acquisition of 3-O-linked glycan around the cleavage site. Although real-time RT-PCR methods targeting specific gene(s) have widely been used to diagnose the COVID-19 patients, however, recently developed more convenient, rapid, and specific diagnostic tools targeting IgM/IgG or newly developed plug and play methods should be available for resource-poor developing countries. Some drugs, vaccines and therapies have shown great promise in early trials, however, these candidates of preventive or therapeutic agents have to pass a long path of trials before being released for the practical application against COVID-19. This review updates current knowledge on origin, genomic evolution, development of the diagnostic tools and the preventive or therapeutic remedies of the COVID-19, and discusses on scopes for further research and effective management and surveillance of COVID-19.

The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a trained immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.

The 2019-Novel Coronavirus has currently gripped the world in terror, affecting 210 countries and territories. Originating from Wuhan, Hubei province, China, the virus has spread so rapidly throughout the world and has already claimed 308,927 lives and is currently afflicting 4.6 million people. The US has over 1.48 million confirmed cases of COVID-19, followed by Spain, Italy, France, UK, Germany, Turkey, Russia, Iran, and China. On careful inspection of the COVID-19 statistics, a peculiar unsettling trend becomes apparent. Western European countries and the US appear to have difficulties in overcoming the catastrophe. In contrast, countries in East Asia, Middle East and mid-Europe have sorted out the situation. Here, we will highlight this trend and propose the importance of infection-genomics (sankramikogenomics), in understanding the susceptibility to COVID-19 and the severity of disease progress. More detailed, systematic evaluation may also identify more susceptible populations. We will also highlight mere 12-fold lower affinity is insufficient to ignore CD147, as interactions occur between tens of spike proteins and equal number of cell surface ACE2 and/or CD147. Thus, both receptors are important to understand sankramikogenomics and severity of COVID-19. The observed ethnic differences in COVID severities may be due to variations in structure or tissue-specific expression (alternate splicing and accessibility) of both the target receptors. Research on both receptors may help in designing improved therapeutic strategies to fight COVID-19. Similar to pharmacogenomics to drug development and precision medicine, Sankramikogenomics will become an important field in other infectious diseases and pathogenicity.

More than 1,000,000 confirmed cases of COVID-19 have been registered worldwide since the beginning of the pandemic in Wuhan on December 2019. The high mortality rate of COVID-19 is associated with age, gender and the presence of comorbidities. Biochemical data have shown that COVID-19 patients develop a local and systemic hyper-inflammatory response associated with poor outcome. Therefore, the understanding of the biological mechanisms underlying SARS-CoV-2-induced inflammation is a compelling need. Following this reasoning, here we will focus on the importance of the progressive age-related development of a pro-inflammatory state (aka inflamm-aging) in the understanding of the unbalanced inflammatory response against SARS-CoV-2 in aged people. In particular, we underpin the role of mitochondrial DNA and genomic DNA telomeric sequences in local and systemic mechanisms of inflammation. Indeed, the leakage of mtDNA out of its natural compartment (i.e. the mitochondrion), into the cytoplasm and in the extracellular environment is a powerful trigger of innate immunity and inflammation, as part of an evolutionary-conserved signaling mechanism of cellular damage (e.g. viral infection). High levels of circulating mtDNA are increased in aged people and set up as inflammatory markers of poor prognosis in intensive care unit patients. In turn, telomeric DNA, which can be released into the cytoplasm and in the extracellular environment upon cell damage, has been proven to exert potent anti-inflammatory activity. Since that aged people (particularly those affected by co-morbidity) are equipped with shortened telomeres, we posit that, in aged people affected by COVID-19 the release of mtDNA, coupled with insufficient telomeric DNA favors the onset of a detrimental inflammatory response. In this regard, we highlight that the mechanism of action of some currently used drugs, as well as potential new ones may be better understood under the light of the above-depicted theoretical framework thus explaining how studies on inflamm-aging may help to understand and combat COVID-19 pandemic.

Introduction: The COVID-19 pandemic is a global crisis, the number of cases and deaths are on a steep incline. This article reviews the possible immunological mechanisms which underlie the disease pathogenesis by looking at the behaviour of previous coronaviruses not only in humans but also other mammals which possibly act as reservoir hosts. Observations: A key aspect of this coronavirus as well as the previous SARS CoV seems to be the importance of host immune response in the pathology and clinical severity of illness caused by them. A hyperactive innate immune state in combination with an exhausted adaptive immune response are possible determinants of severe illness. Conclusion: There is a possibility that the current SARS CoV 2 has immune evasive tactics similar to SARS CoV in its repertoire, since they share a 76% homology. These might have been learnt behaviour from long periods of persistence in their reservoir hosts and they may be the reason behind the dysregulated immune response evoked in humans. That in turn is highly likely to be one of the factors which govern disease severity. With this in mind we want to bring the medical community’s attention to a ‘hit early, hit hard’ intervention as a possible strategy to modify the course of the disease and bring down the numbers of severe sufferers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.

The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.

As of 26 March 2020, Pakistan had 1179 cases of COVID-19, with most 421 cases from Sindh, 394 cases, 131 cases, 123 cases, 84 cases, 25 cases and 01 cases from Punjab, Balochistan, Khyber Pakhtunkhwa, Gilgit-Baltistan, Islamabad Capital Territory, and Azad Jammu and Kashmir respectively. Travel-related cases were the main source of SARS-CoV-2 infection during the early phase of the pandemic in Pakistan. Nevertheless, cases of local virus transmission are increasing day by day. As of 26 March 2020, nine deaths have been reported from COVID-19. The case fatality rate is 0.8%, which is less compare to China, Italy, USA, and Iran. The SIR (Susceptible-Infected-Recovered) model of epidemiological analysis predicts that almost 90 million population will be infected in the coming days with 5% critical cases that need health care facilities. However, the Pakistan health care system cannot provide services to this much population. Hence, we need to act timely to reduce this number by restricting local transmission of the disease. This can be done by mass testing, quarantine, isolation and social distancing of the active coronavirus cases in Pakistan. Moreover, better communication between the authorities is very much required to control disease transmission.

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

In 2020, the pandemic caused by the Coronaviruses (CoV) that are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV2). The Coronavirus disease (COVID-19) is a new strain that was discovered in 2019 and has not been previously identified in humans. It is the high time to investigate the quantitative and/or qualitative genomic informations of the virus SARS-CoV2 in order to strengthen the healthcare facility to fight against this viral disease. In this article, a through quantitative understanding of the purine and pyrimidine spatial distribution/organization of all 89 complete sequences of SARS-CoV (available as on date in the NCBI virus database, is made using different parameters such as fractal dimension, Hurst exponent, Shannon entropy and GC content of the nucleotide sequences of the genome of SARS-CoV2. Also a cluster among all the the SARS-CoV sequences of nucleotide have been made based on their phylogeny made through their closeness (Hamming distance) based on respective purine-pyrimidine distribution.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

The rapid development of 2019-2020 Wuhan seafood market pneumonia currently posed a major public health concern in China. Genome sequencing identified a novel beta-coronavirus closely related to SARS-CoV, named 2019-nCoV by WHO, as the cause of this pandemic disease. Viruses with single stranded RNA genome are prone to evolve quickly by accumulation of mutations, such as SNV, INDEL and cross viral recombination, aiding fast transmission among hosts and cross species. Here we collected related genome sequences and investigated variations shared by different strains of 2019-nCoV, identified reoccurrence of SNV mutations in clusters of patients, an indication of rapid evolution of 2019-nCoV at the transmission from animal host to human. The information collected herein would help to understand the dynamics of current pandemic.

Knowing the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many places during the first wave of COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain), during “Falles” mass gathering events in March 2020, a cross-sectional study was performed in June 2020 querying public health register. Logistic regression models were used. From a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak by anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), thus an underreporting of 92.3% (95% Confidence Interval [CI] 89.5%-94.6%), 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting were no medical assistance for COVID-19 disease, adjusted odds ratio [aOR] 10.83 (95% CI 2.49-47.11), no chronic illness, aOR=2.81 (95% CI 1.28-6.17), middle and lower social classes, aOR=3.12 (95% CI 1.42-6.85), younger age, aOR=0.97 (95% CI 0.94-0.99), shorter duration of illness, aOR=0.98 (95% CI 0.97-0.99). To improve surveillance, studies of representative population samples are necessary to estimate the magnitude of future epidemics, and novel approaches are recommended.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build its nucleocapsid envelope and to fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if the treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFA), fatty acid of the phospholipids (FAPL), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HS). COVID-19 patients showed a decrease in Vit E, TPLs, FAPL and TFA in serum in comparison to HS (p≤0.01) and Vit E treatment restored their levels (p≤0.04). Likewise, there was an increase IL-6 and CRP in COVID-19 patients in comparison with HS (p≤0.001) and the treatment with Vit E decreased their levels (p≤0.001). Treatment with Vit E contributes to restore the modified profile of the PLs in the SARS-CoV-2 infection and this leads to a decrease of OS and of the inflammatory process.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

The emergence of the SARS-CoV-2 Variant of Concern (VOC) Omicron has been characterized by an explosive number of cases in almost every part of the world. The dissemination of different sub-lineages and recombinant genomes also led to several posterior waves in many countries. The circulation of this VOC and its major sub-lineages (BA.1 to BA.5) was monitored in community cases and in international travelers returning to Venezuela, by a rapid partial sequencing method. The specific sub-lineage assignment was performed by complete genome sequencing. Epidemic waves of SARS-CoV-2 cases were observed among international travelers during 2022, a situation not seen before December 2021. The succession of the Omicron VOC sub-lineages BA.1 to BA.5 occurred sequentially, except for BA.3, which was almost not detected. However, the sub-lineages generally circulated two months earlier in international travelers than in community cases. The diversity of Omicron sub-lineages found in international travelers was related to the one found in the USA, consistent with the most frequent destination of international travel from Venezuela this year. These differences are compatible with the delay observed in Latin American countries in the circulation of the different lineages of the Omicron VOC.

Due to species barriers and poor adaptability to new host environments, few pathogens cause global pandemics. But, SARS-CoV-2 is one exception with its high transmissivity and delayed onset of symptoms. Fortunately, the world was able to tap on the technologies especially the maturing RT-qPCR designed to combat SARS to launch an initial offensive on SARS-CoV-2. These initial efforts may have bought time for scientists to develop more refined diagnostic tests that specifically target SARS-CoV-2. This article describes the effort put forth by the biotech industry and academia in Singapore to develop diagnostic tests that aid the early detection of positive cases, and thereby help contain the virus. Direct tests such as RT-qPCR and antigen rapid test profile the virus nucleic acid and surface proteins, respectively. But, of equal importance in case detection and treatment is serological tests that measure the relative abundance of IgM and IgG which is indicative of infection phase and quality of immune response in positive cases. Other tests such as isothermal amplification, CRISPR-based diagnostics and breath tests are also in development or at initial field deployment, and would undoubtedly provide valuable use experience useful for the development of molecular assays to detect and combat the next pathogen of global concern.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization and their expressional profile in different tissues was studied. These in-silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p<0.010 for hand washing). The risk perception of COVID-19 infection had a slight direct relationship with preventive behaviors (B=0.28, p=0.021 for total behavior; B=0.13, p=0.015 for hand washing), with the exception of the preventive behavior of using additional protection at work (p=0.339). We found that fear and risk perception are associated with increased practice of hand washing and use of additional protection at work. Further studies are required on the influence of working conditions, job performance and the occurrence of mental health problems in frontline personnel with regard to COVID-19.

The disease COVID-19 is brought on by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) First appeared in China in December 2019 and quickly spread around the world after being declared a worldwide pandemic by the World Health Organization in March 2020. COVID-19, Medical Laboratory Professionals, SARS-COV-2, Diagnostic, Importance and difficulties for testing were the selected terms to search the databases of PubMed and Google Scholar for previously published material. Many diagnostic tests are applied in corona virus detection like Droplet Digital PCR (ddPCR), Multiplex PCR, Loop-mediated Isothermal Amplification (LAMP) and more. There is a lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies. Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.

Currently SARS-CoV-2 is spreading around the world as an Omicron strain. Recently, the Omicron variants (BQ.1 and BQ.1.1) were identified as novel Variants of Concern. UpToDate, there is little information about the Omicron Variants BQ.1 and BQ.1.1. The widely altered Omicron variants are spread globally, providing a high risk of infection surges with devastating consequences in some areas. The Omicron type of SARS-CoV-2 has a harm risk of reinfection, according to early reported findings. COVID-19 Variants particularly, BQ.1 and BQ.1.1 have gained global attention and caused a worldwide sensation since their discovery. Therefore, this communication discusses the present status of COVID-19 Variants BQ.1 and BQ.1.1, and their consequences.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of monoclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerful therapeutic potential. Methods: Layers were immunized twice with 14-day interval using purified RBD of SARS-CoV-2. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgY to RBD was measured by indirect ELISA. Neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry strain using fluorescence and cell viability assay. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bind RBD of S protein of SARS-CoV-2 in situ, neutralize the virus in vitro, and lower viral RNA amplification without significant alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicated that chicken polyclonal IgYs can be attractive targets for pre-clinical and clinical development for rapid management of outbreaks of emerging and re-emerging viruses.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.