The current pneumonia epidemic could evolve into a pandemic on a global scale if not effectively contained. The COVID-19 virus possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in SARS-CoV-2. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. As the content of essential amino acids in the open reading frame of SARS-CoV-2 reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Furthermore, several proteins of SARS-CoV-2 possess high valine plus glycine content which is implicated in heart disease, justifying the aforementioned approaches.

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as “Whether there are differences based on gender in risk and severity of infection or mortality rate?” and “What are the biological explanation and mechanisms underlying these differences?” Emerging evidence has proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. From an immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.

Our first modern global pandemic is caused by a nanosized lipid vesicle, called SARS-CoV-2. Its molecular structure and biogenesis have remarkable similarities with Extracellular Vesicles (EVs, most notably exosomes) that are constantly shed by all cells during their life. Their resemblance may not be a coincidence. Growing body of evidence has shown that EVs have significant roles in various biological processes, including viral infection, transmission and anti-viral response. Drawing comparison with the virus might shed light on how we could fight the COVID-19 disease. This may include novel EV research and diagnostics technologies as well as novel EV-based treatments.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

The physical environment plays an important role in the transmission of respiratory infections like Covid-19. To find relevant articles on environmental factors influencing respiratory infection outbreaks, we searched Pub med Central on the following topics: 1. Environmental pollution causing coronavirus fatality- 73 results, relevant 1 article, 2. Environmental factors affecting Covid-19, 149 results from which there were 6 relevant articles, 3. Impact of air pollution on Covid-19 fatality, 10 results, relevant 3 articles, 4. Environmental factors affecting respiratory viruses- 10646 results were obtained, 2 relevant articles. We searched Google scholar on environmental factors affecting Covid-19 transmission and found 7 relevant papers. We excluded the duplicates in each of the key words search. Date of search was on 20^th April 2020. All articles included in results were scrutinized and relevance of articles was based on their content that discussed meteorological and physical environment factors in the spread and severity of Covid-19. We have discussed factors like air pollution, smoking, air temperature, humidity and air velocity as contributing factors. If meteorological factors are conducive to spread in a particular area, we need protective measures way before a respiratory infection outbreak occurs. Covid-19 is a lesson learnt the hard way, and we must enable people to practice hygienic practices with limited resources but high level of protection that it provides. Air pollution control can prevent priming of respiratory system which shall further protect from pulmonary infections.

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of betacoronaviruses in the aftermath of the 2002-03 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-20 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind, allowing the follow up of disease spread and transmission dynamics in near real time. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2.

As the first initiative of its kind in Algeria, here is presented a solar-powered mobile “Ultraviolet Germicidal Irradiation” disinfection unit (UVGI) based on a special germicidal ultraviolet-C (UVC) radiator. The system was designed to disinfect several objects such as: medical tools, reusable masks, face-shields, gloves, phones, laptops, keys, money and many other portable devices that need to be disinfected/sterilized. It offers the advantage of complete autonomy through the built-in photovoltaic (PV) system that includes a solar panel, a gel battery, a charge controller and a power inverter. The system provides an extra 220V-50Hz outlet with 375VA maximum power to be used when energy is needed. The system is easily scalable to generate higher ultraviolet dosages by adding more UVC lamps. The chemical-free germicidal UVC sanitizing method employed by this device effectively disactivates a very wide range of microorganisms (microbes, bacteria and fungi and viruses including the actual SARS-CoV-2 that causes COVID-19 respiratory disease) and it has several advantages in comparison to chemical-based sanitizing methods. The total cost to make this open source device is below 1000 € and is easily customizable and scalable. This device is an open source, secure and fast equipment for objects and surface disinfection. The device will be fully automated by adding PIR sensors or remote control after further funding will be received.

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with M protein of SARS-CoV; whereas, the similarity was only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of the M protein having a sugar transport-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the semiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

The constant news about the corona virus is scary. It is not possible to separate treatment for Cancer due to COVID-19. An effective treatment comparison strategy is needed. We need to have a handy tool to understand cancer progression in this unprecedented scenario. Linking different events of cancer progression is the need of the hour. It is a methodological challenge. We provide the solutions to overcome the issue with interval between two consecutive events in motivating head and neck cancer (HNC) data.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

Family doctors can have an active role in identifying significant population needs and solutions. During COVID-19 epidemic, patient home monitoring with pulse oximetry has been a key aspect of care of patients. However, pandemics bring shortage medical equipment such as pulse oximetry. Through the local maker community in a matter of days four “smart” pulsoximeters were created and built. Following Internet of Things principles, the pulsoximeters were programmed to transmit recorded data through Wi-Fi, in real time, directly to the doctors. Each protype pulsoximeter served a family doctor during the pandemic. Building instructions were shared in maker-oriented websites, potentially leading to additional small-scale productions.

Chronic noncommunicable diseases (CNCDs) have been a major public health concern worldwide, especially diabetes, cardiovascular disease, chronic obstructive pulmonary disease, hypertension, in addition to obesity, which is even more worrying when the subject involves the covid-19 pandemic, because such incidences correlate with the need for intensive care units, including the possibility of death of the patient. Therefore, for countries with the highest numbers of critical cases, it is important to assess the incidence of these diseases to guide the public that most needs guidance on public policies for social isolation.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

The World Health Organization has defined the outbreak of the new coronavirus as a public health emergency of international concern. The average age of patients affected by the disease caused by the virus ranges from 49 to 59 years. The symptoms of coronavirus disease 2019 (COVID-19) infection include fever, cough, acute respiratory disease, and, in severe cases, the disease may progress to pneumonia and renal failure that may lead to death. Many oral and maxillofacial hospital procedures produce aerosol and droplets contaminated by blood, bacteria, and viruses. The purpose of this study is to gather recommendations from health authorities and scientific articles in order to educate surgeons regarding the procedures to assist and treat in oral and maxillofacial surgeries. The objective is to prevent the transmission of COVID-19 during the treatment of patients in urgent and emergency situations. The study’s methodology used the guidelines provided by the Brazilian College of Oral and Maxillofacial Surgery, in addition to the recommendations and epidemiologic data from national and international health authorities. The implementation of special precautions in oral and maxillofacial surgeries may elucidate questions related to the transmission of the disease by asymptomatic carriers and help control the spread of the virus.

The human angiotensin-converting enzyme 2 (ACE2) has a crucial role on blood pressure control; however, ACE2 is also the primary SARS-CoV-2 (S domain) virus receptor. Inhibiting or even reducing the expression of the native ACE2 might diminish the viral entry into the cells, but may cause a failure of ACE2 biological activity, primarily in patients with comorbidities, including diabetes mellitus or hypertension. Since the ACE2 catalytic site and the SARS-Cov-2 receptor are distinct, we designed a Crispr-Cas9 model system, predicting the respective sequences for a guide RNA (gRNA) and a single-stranded oligo dideoxy nucleotide (ssODN), to introduce point mutations into the exon 1 of the human ACE2 gene, which encodes the alpha-helix, implicated on the binding of the SARS-CoV-2 envelope S protein. Protein modeling predicted that the specific substitutions of residues Phe28, Lys31, and Tyr41 for Ala at the ACE2 alpha-helix do not significantly alter ACE2 native conformation. The analysis of the impact of these mutations on ACE2 receptor function predicted a weakening of the binding of the SARS-CoV-2 protein S. An experimental genome editing of cells based on these Crispr-Cas9 elements might reduce the SARS-CoV-2 ability to enter the epithelial cell, preserving the biological activity of ACE2 enzyme.

Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. Methods: We performed a systematic review of the literature (PubMed) for studies published until April 25. Studies were included into the analysis if they satisfied all of the following criteria: 1. To present hospitalized patients with COVID-19. 2. To classify patients into less and more severe disease, irrespective of the severity definition (defined as “adverse ourtcome”). 3. To present data on the smoking status, separately for each severity classification. We identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted, population-based expected prevalence by calculating Prevalence Odds Ratio (POR). The association between current, compared to non-current and former, smoking and adverse outcome was examined by calculating Odds Ratio (OR). All analyses were performed using random-effects meta-analysis. Results: Among 6515 patients, 440 of whom were current smokers, the pooled prevalence of current smoking was 6.8% (95%CI: 4.8-9.1%) and the POR was 0.21 (95%CI: 0.16-0.26, P < 0.001). In Chinese studies only, the POR was 0.22 (95%CI: 0.17-0.27, P < 0.001). Current smokers were more likely to have an adverse outcome compared to non-current smokers (OR: 1.53, 95%CI: 1.06-2.20, P = 0.022). However, they were less likely to have an adverse outcome compared to former smokers (OR: 0.42, 95%CI: 0.27-0.74, P = 0.003). Conclusion: An unexpectedly low prevalence of current smoking was observed among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared to non-current smokers but lower odds compared to former smokers for an adverse outcome. The possibility that nicotine may have a protective effect in COVID-19 which may be masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored.

The state of community lock-down due to COVID-19 pandemic caused restricted movements of people. There are existing evidence of the negative impact of quarantine and isolation to the mental health of a person in different contexts. A scoping review of literature using Google Scholar was conducted to discover records about the public mental health while in a community quarantine due to COVID-19 pandemic. A methodological approach suggested by Arksey and O’Malley was utilized. It comprised (a) identifying the research questions, (b) identifying relevant literatures, (c) selecting literature, (d) charting the extracted data, and (e) summarizing, analyzing, and reporting the results. As of April 17, 2020, there were only 4 original articles found that discuss psychosocial aspect of the COVID-19 crisis. After an online survey, they present evidence that (1) there is an outward change in the people’s behavior toward self-care during the pandemic and (2) trusting the community governing bodies can minimize the level of anxiety and stress. Other literatures found are original articles in preprint (n=8), letters, commentaries, editorial (n=6), review paper (n=4), and WHO guideline (n=1). It is evident that the psychosocial aspect of COVID-19 crisis needs more attention from the scholars and a large research gap can be lessened trough expansion of online platforms.

As the novel COVID-19 disease spreads around the world, the most affected population are those who suffer from the most common chronic diseases, such as obesity, hypertension, and type 2 diabetes, which are quite associated with the so-called age-related diseases. On the other hand, since the Spanish influenza outbreak, humanity has not experienced an infectious disease that synergizes so quickly with chronic diseases, making it mortal for those individuals with comorbidities. In this context, COVID-19 is challenging for health systems all around the world due to the high prevalence of chronic diseases. Nowadays, we are facing the beginning of a new era in which health infectious and chronic diseases meet. Therefore, epidemiologic and biomedical researchers must work together to solve further contingencies, and politicians should direct science-centered decisions on public health. In the present paper, we make an urgent call to learn from the COVID-19 lessons in order to mitigate the chronic diseases prevalence and to address the influence of the infectious diseases on the aging process; since we are about to begin the Decade of Healthy Aging.

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.

The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop mediated amplification (LAMP) and recombinase polymerase amplification (RPA) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralised laboratory and prolonged turn-around-time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. More so, it is cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.

The most striking and dramatic catastrophe, as on April 2020, is - COVID - 19. Understanding of the COVID-19, the causing agent- the virus and the resultant causalities are still evolving. Till now, there is no specific treatment, no vaccine for the COVID-19. At this stage, what is utmost important now to face the disaster is to put emphasis on the preparedness and responses: research to discover vaccine, antivirals as soon as possible. Till then, it is necessary to put emphasis on infection preventive and control measures like to avoid close contact of infected people showing symptoms of respiratory diseases, hand hygiene and coughing etiquette. To make the infection preventive and control measures a success, the followings are to make success: ‘quarantine’ ‘isolation’, ‘travel bans’, ‘cordon sanitaire’ and ‘social distancing’ measures. The tools of modern information technology could help the authority to manage and monitor the preventive measures. Above all, preventive and control measures will not be successful if we fail to make aware the common people about the fatality of the COVID - 19. So, rapid preparedness and responses to COVID-19 are critically essential to face such disaster. Not a single moment is to waste!

In this paper we first provide a primer on SARS-CoV-2 and Covid-19 delineating the etiopathogenesis, epidemiology, clinical manifestations and the natural history of the disease. We then trace the evolution of the Covid-19 pandemic highlighting the characteristics of the epidemic in China where the pandemic originated, select countries of Europe which peaked during April, and Brazil, US and India where the pandemic has taken serious turns recently. We also project some possible trajectories for the mega cities of India based on the demographic characteristics of these cities in comparison to New York city. This is an updated version of the article from mid-April published online.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Covid-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The covid-19 7098 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na⁺ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR.

COVID-19 disease outbreak was started in the December, 2019 in the Wuhan city of China which is also known as the largest transportation hub of China. During the spring festival of China the situation become epidemic. Soon, the virus is imported to many regions including the low income countries. Till now, 234073 infected reported cases of the COVID-19 in the world with the total of 9840 deaths (March 20, 2020). The common symptoms of the COVID-19 are the cough, high fever, sore throat, fatigue and breathlessness. The disease is found to be mild in most of the people, some of cases reported to the pneumonia also with multi organ dysfunction and acute ARDS (acute respiratory distress syndrome). It is found that the incubation period for the infection is 2-14 days which is usually 4 days in maximum of cases. India has reported 283 cases of COVID-19 infections till now with 4 deaths. India is still at stage 2 on local transmission as per WHO report 60. WHO reported 60 clearly stated that there is no community transmission occurred in India yet which can be prevented by the avoiding mass gathering and proper screening of the people. Govt. of India has taken many initiatives to minimize the spread of COVID-19 infection in the country. The infection rate of the COVID-19 in India remains low related to population size of the country. It is because of fast government action to quarantine the suspected people and shut down all its borders. There is a great slowdown in the global economy due to COVID-19 attack which is likely to costs around $1 trillion. The spread of COVID-19 infection can be reduced by minimizing the H-H transmissions. Still there is need of Anti-n-CoV drug development which can replace the supporting therapies for the treatment of infection.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

Background: Coronavirus disease 2019 (COVID-19) pandemic are causing significant damages to many nations. For mitigating its risk, Japan’s Prime Minister called on all elementary, junior high and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing disease burden has not been investigated. Methods: We used daily data on the report of COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time series analysis were conducted using Bayesian method. Local linear trend models with interventional effect were constructed for number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of intervention start to appear 9 days after the school closure; i.e., on March 9. Results: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, mean coefficient α for effectiveness of the measure was calculated to be 0.08 (95% credible interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with rather wide credible interval. Sensitivity analyses using different dates also showed similar results. Conclusions: School closure carried out in Japan did not show the effectiveness to mitigate the transmission of novel coronavirus infection.

Humanity’s social and economic development has been challenged by a range of adversities over the millennia that have caused widespread and unimaginable suffering. At the same time, these challenges have forced humans to evolve more wisely, overcoming adversity through creativity and leading to advancements in science and technology, medicine, ethics and legal systems, and socio-political systems. The dynamics of risks and opportunities caused by COVID-19, in the built, cyber, social and economic environments, present opportunities for deepening our understanding of resilient and sustainable development and infrastructure. This article reflects on five lessons that COVID-19 is teaching us about what it means to develop sustainably through the lens of transportation: (1) sustainable development planning and analytical frameworks must be comprehensive, for long-term sustainability; (2) multi-modal transportation is a superior vision for sustainable development than any one particular mode; (3) tele-activities are part of an effective infrastructure sustainability strategy; (4) economic capital is critically important to sustainable development even when it is not a critical existential threat, and, (5) effective social capital is essential in global disaster resistance and recovery, and can and must be leveraged between fast-moving and slow-moving disasters. Resilient and sustainable infrastructure will continue to be critical to addressing evolving natural and man-made hazards in the 21^st Century.

Nearly three months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 550,000 confirmed cases and more than 25,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In the kingdom of Saudi Arabia, unprecedented precautionary strict measures were applied to slow virus entry and to mitigate the risk of the outbreak. Here, we review the experience learned during the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemic in Saudi Arabia, which has been in the country since 2012, and is expected to have helped the country to be well prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

A novel strategy is presented for reliable diagnosis and progression prediction of diseases with special attention to COVID-19 pandemy. A plan is presented for how the model can be implemented worldwide in healthcare and how novel treatments and targets can be detected. The idea is based on poikilosis, pervasive heterogeneity and variation at all levels, systems and mechanisms. Poikilosis in diseases can be taken account in pathogenicity model, which is based on distribution of three independent condition measures – extent, modulation and severity. Pathogenicity model is a population or cohort-based description of disease components. Evidence-based thresholds can be applied to the pathogenicity model and used for diagnosis as well as for early detection of patients in risk of developing the most severe forms of the disease. Analysis of patients with differential course of disease can help in detecting biomarkers of diagnostic and prognostic significance. A practical and feasible plan is presented how the concepts can be implemented in practice. Collaboration of many actors, including the World Health Organization and national health authorities, will be essential for success.

The global pandemic of COVID-19 accounts for more than 14,000 deaths worldwide. However, little is known about the host genetics interaction with infection and COVID-19 progression. To better understand the role of host genetics, we review the current literature, aggregate readily available genetic resources, and provide some updated analysis relevant to COVID-19 and associated phenotypes. Using the unrelated individuals in UK Biobank (total n = 337,579 across 5 populations), we aggregate human leukocyte antigen and ABO blood type frequencies. We find significant and consistent risk reduction of blood group O reported in Zhao et al. and encourage broad sharing of ABO blood type frequencies that are readily accessible across COVID-19 with mild, moderate, and severe/critical symptoms for robust inferences at https://tinyurl.com/abo-covid19. In addition, we generate polygenic risk scores (PRSs) weights for 29 blood measurements, including clinically relevant haematological measurements for COVID-19, such as lymphocyte count and percentage. Focusing on the 8 most COVID-19 clinically relevant blood measurements, we performed PRS-PheWAS analysis across 44 disease antigen measurements (n = 6,643 unrelated individuals in White British group), infectious diseases and acute respiratory infections (n = 20,928 cases and 349,000 controls across 3 population groups) and deaths (n = 1,846 cases and 368,082 controls), recorded in hospital inpatient record and death registry data, respectively, in UK Biobank, and find host genetic PRS associations with disease risk. Taken together, we anticipate these resources (https://github.com/rivas-lab/covid19) will aid in improving our understanding of host genetic risk factors playing a role in SARS-CoV-2 infection and COVID-19 disease severity.

The outbreak of Coronavirus disease 2019 (COVID-19) has posed a significant concern in many countries due to the rapid rate of transmission between humans. Taking advantage of the experience of the last epidemics in 2002 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), some regions of the world were well- prepared for the new outbreak. However, other countries needed to be adapted to the situation promptly. Many management strategies were established, and some restrictions were introduced in some regions. In this review, we aimed to determine countries’ public responses to the epidemic of COVID-19 and how they developed administrative approaches towards the outbreak.

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

Background Critical patients with novel coronavirus pneumonia ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.

Background: In 80% of patients, COVID-19 presents as mild disease^1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia³, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression⁴. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV^5,6 SARS-CoV-1^7-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) ¹¹ demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease³ and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion^{12 13}. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

The disease COVID-19 is highly infectious, and infectious in asymptomatic incubation period. The national epidemic development has been effectively controlled and continues improving, especially in areas outside Hubei province. Such periodical results were achieved by the joint efforts of the whole society, including not only the hard work and dedication of the front-line medical workers but also the active cooperation of the general public. The strict epidemic prevention and control measurements have brought remarkable control results. In the present study, the basic infection number of the coronavirus R0 (basic replication number of the infection) before and after prevention and control measurements was simulated to elaborate the measurements of the Chinese government on epidemic prevention and control, providing reference for the people around the world.

Assessment of the percentage of disease infected lung volume using computed tomography (CT) images can play an important role to detect lung diseases and predict disease severity. However, manual segmentation of disease infected regions from many CT image slices is tedious and not feasible in clinical practice. To help solve this clinical challenge, this study aims to investigate a new strategy to automatically segment disease infected regions and predict disease severity. We employed a public dataset acquired from 20 COVID-19 patients, which includes manually annotated lung and infections masks, to train a new ensembled deep learning (DL) model that combines the five customized residual attention UNet models to segment disease infected regions followed by a Feature Pyramid Network (FPN) model to classify severity stage of COVID-19 infection. To test potentially clinical utility of new model, we first gathered and processed another set of CT images acquired from 80 Covid-19 patients. Next, we asked two chest radiologists to read CT images of each patient and report the estimated percentage of infected lung volume and disease severity level. Additionally, we asked radiologists to rate acceptance of DL model-generated segmentation results using a 5-scale rating method. Data analysis results show that agreement between disease severity classification is &gt;90% in 45 testing cases. Furthermore, &gt;73% of cases received the high rating score from two radiologists (scored more than 4). This study demonstrates feasibility of developing a new DL-model to efficiently provide quantitative assessment of disease severity based on the automated segmentation of the disease infected regions to support improving efficacy of radiologists in disease diagnosis.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

Abstract: The COVID-19 pandemic has brought about significant psychological challenges, particularly depressive and anxiety-related behaviors in those who have recovered from the virus. This study focuses on individuals aged 30-75+ to understand the prevalence, severity, and impact of these symptoms. By exploring their lasting consequences and potential risk factors, we aim to provide valuable insights for healthcare and mental health professionals, guiding the development of effective support systems to address the psychological aftermath of COVID-19. In this study, a quantitative research design was used to investigate the effects of depressive and anxiety behaviors in patients aged 30-75+ who had experienced COVID-19. The research employed a cross-sectional approach, collecting data at a specific time to assess the prevalence and severity of depressive and anxiety symptoms in the target population. A total of 422 patients were recruited through convenience sampling from various sources, including healthcare facilities, community organizations, and online platforms. Inclusion criteria encompassed individuals aged 30-75+ who had tested positive for COVID-19 and had recovered from the infection. Those with pre-existing mental health conditions significantly affecting depressive and anxiety symptoms were excluded. The sample was diverse in terms of age, gender, employment status, education level, marital status, and past chronic problems. Data collection involved administering standardized questionnaires, such as the Patient Health Questionnaire (PHQ-9) for depressive behaviors and the Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety behaviors. These questionnaires assessed symptom severity, while demographic variables were collected separately. The collected data underwent analysis using the Statistical Package for the Social Sciences (SPSS) software, encompassing descriptive statistics, reliability assessments, normality tests, non-parametric tests for demographic comparisons, correlation analyses, and linear regression. Ethical approval and informed consent were obtained, ensuring participant confidentiality and data privacy. Several limitations were acknowledged, including the cross-sectional design's inability to establish causal relationships, potential selection bias due to convenience sampling, susceptibility to response biases with self-report measures, and assumptions and limitations inherent in statistical tests. Overall, the study aimed to provide insights into the effects of depressive and anxiety behaviors in COVID-19 survivors aged 30-75+ and contribute to the development of targeted interventions and support services for this population. This study explored the impact of depressive and anxiety behaviors in COVID-19 survivors aged 30-75+. It involved data collection through validated questionnaires and rigorous statistical analysis. The findings underscore the importance of tailored interventions and support systems to address the long-term psychological effects of the pandemic. Healthcare professionals, researchers, and policymakers must collaborate to prioritize mental well-being and allocate resources accordingly, ultimately improving the quality of life for survivors.

(1) Background: Several chronic respiratory diseases could be a risk factor for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunctioning of the respiratory cilia; We aimed to investigate if some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms in a cohort of PCD subjects; (2) Methods: Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms and vaccinations; in case of infection, they also filled out a SNOT-22 and ARTIQ questionnaires; (3) Results: Forty PCD adult patients (mean age 36.6 ± 16.7 years, 23 females) participated to the study, out of which 30 % had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistic significant difference (p=0.03) was observed in body mass index (BMI), that was higher in the COVID-acquired group (23.2 ± 3.3 vs 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of PAV allele towards SARS-CoV-2 infection; (4) Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype type does not affect SARS-CoV-2 infection.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

Immortal-time bias (ITB) is known to be common in cohort studies and distorts the association estimates between treated and untreated groups. We used data from the last of two large studies in an Italian province on COVID-19 vaccines safety and effectiveness incurred this bias, and aligned the entire population on a single index date, to correct the ITB. We considered the "all-cause deaths" outcome to compare the survival curves between the unvaccinated group and the various vaccination statuses. The all-cause deaths Hazard Ratios in univariate analysis for unvaccinated (reference) versus vaccinated with 1, 2, 3/4 doses were 0.88 (CI95: 0.78 –1.00; p-value 0.044), 1.23 (1.16–1.32; p-value ≤0.001) and 1.21 (1.14–1.29; p-value ≤0.001), respectively. The multivariate values were 2.40 (2.00–2.88; p-value <0.0001), 1.98 (1.75–2.24; p-value <0.0001), 0.99 (0.90–1.09; ns). The possible explanations of the trend of the Hazard Ratios as vaccinations increase could be a harvesting effect; a calendar-time bias, accounting for seasonality and pandemic waves; a case-counting windows bias; a healthy-vaccinee bias; or some their combination. With two and even with 3/4 doses the calculated Restricted Mean Survival Time and Restricted Mean Time Lost have shown a small but significant downside for the vaccinated populations.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

Objective: The Covid-19 pandemic has raised significant concerns about public health, particularly in terms of mental well-being due to heightened fear and uncertainty. The findings of this study are based on a survey conducted to evaluate the mental health status of the general population in Croatia during the Covid-19 pandemic. Methods: A survey conducted randomly and cross-sectionally included 588 respondents from all 21 counties in Croatia. The survey gathered demographic data and assessed various factors related to pandemic response measures and mental health using the Mental Health Continuum-Short Form (MHC-SF) scale. Results: Despite feeling adequately informed about Covid-19 (76.0%), most respondents (60.8%) expressed concerns about their loved ones during the pandemic. There were significant numbers who felt there was no risk of infection (50.9%) or believed they would not get infected (40.2%), while 72.4% were content with government measures. Statistical analysis indicated that mental health was not significantly different between genders, but age-related differences were evident, with those under 21 experiencing the most distress. The lowest level of psychological and social well-being was observed in respondents who were unemployed. Conclusions: The study identifies vulnerable groups in the Croatian population during the pandemic, including younger individuals, those on parental leave, students, and the unemployed, who exhibited worse mental health. The importance of implementing targeted mental health interventions to support these vulnerable groups is highlighted by these findings.

Throughout the COVID-19 pandemic, masks have been promoted as an important tool for reducing SARS-CoV-2 transmission. However, even though masks are plausible experimental interventions, their mechanistic effectiveness has not been validated by randomized clinical trials (RCTs), with reduction risks of just 1.1-fold (11%) or less. Several meta-analyses have suggested that masks effectively reduce viral transmission, but all of them rely heavily or exclusively on observational data. Indeed, there is a strong inverse correlation between the effectiveness of masks and the number of RCTs included in the meta-analysis. RCTs on alternative therapies often show similar low levels of effectiveness. Thus, masks can be compared with potential new drugs or therapies that failed clinical trials despite showing mechanistic evidence.

This study aimed to determine whether the EQ-5D-5L tool captures the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea in patients with post COVID-19 conditions, and if adding these symptoms improves the explained variance of the health-related quality of life (HRQoL). In this exploratory cross-sectional study, two cohorts of Swedish patients (n=177) with a history of COVID-19 infection answeared a questionnaire covering sociodemographic characteristics, clinical factors and HRQoL assessed using EQ-5D-5L with the Visual Analogue Scale (EQ-VAS). Spearman rank correlation and multiple regression analyses were employed to investigate the extent to which the most common persistent symptoms such as fatigue, memory/concentration problems and dyspnea were explained by the EQ-5D-5L. The explanatory power of EQ-5D-5L for EQ-VAS was also analysed, both with and without inclusion of symptom(s). We found that the EQ-5D-5L dimensions partly captured fatigue and memory/concentration problems but performed poorly in capturing dyspnea. Specifically, the EQ-5D-5L explained 55% of the variance in memory/concentration problems, 47% in fatigue and only 14% in dyspnea. Adding fatigue to the EQ-5D-5L increased the explained variance of the EQ-VAS by 5.7%, while the addition of memory/concentration problems and dyspnea had a comparatively smaller impact on the explained variance. Our study highlights the EQ-5D-5L’s strength in capturing fatigue and memory/concentration problems in post COVID-19 patients. However, it also underscores the challenges in assessing dyspnea in this group. Fatigue emerged as a notably influential symptom, significantly enhancing the EQ-5D-5L's predictive ability to for the EQ-VAS score in these patients.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Background: During the pandemic, Emergency departments were overcrowded with critically ill patients and confronted ethical dilemmas to assign respiratory support to them due to scarce resources. Quick tools to evaluate patients at admission were needed; many scores were used but inaccurate to predict outcomes. The Rox Index is an easy and fast score that reflects the respiratory status in acute respiratory failure patients, this score could predict the outcome of covid 19 patients. Hypothesis: The 24-hour difference in the Rox Index discriminate accurately the mortality and needs for mechanical ventilation of patients with covid-19. Methods: Study design: Prospective analytic study. Population: 204 Patients admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The Rox Index was calculated at admission and 24h later, the difference was used to establish the outcome, a logistic regression model adjusting for age, sex, presence of comorbidities and disease severity to build and perform ROC analysis. Results: Difference in respiratory ROX Index between admission and 24h is a good predictor for death AUC 0.92 and for mechanic ventilation AUC: 0.75. Each decrease in one unit of the difference at 24h had an Odds Ratio for death risk: 1.48 (95%CI: 1.31-1.67) and for mechanic ventilation: 1.16 (95%IC: 1.1-1.23). Conclusion: The 24-hour variation of Rox Index has good predictive value and allows healthcare professionals to identify which patients will benefit from invasive treatment, especially in low resource settings where emergency physicians deal with survival.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Despite widespread vaccination, early treatments, and improved understanding of the disease, the effects of SARS-CoV-2 infection remain significant worldwide. Many patients still suffer from severe COVID-19, necessitating admission to intensive care units. Remdesivir is a primary treatment option among viral RNA polymerase inhibitors for hospitalized SARS-CoV-2 patients. However, there is a lack of studies examining factors influencing its effectiveness in this context. We conducted a retrospective study throughout 2022, analyzing clinical, laboratory, and sociodemographic data from 252 hospitalized COVID-19 patients treated with remdesivir. Six machine learning algorithms were compared and validated to predict factors associated with the loss of clinical benefit from remdesivir in terms of mortality and hospital stay. Data were extracted from electronic health records. The eXtreme Gradient Boost (XGB) method achieved the highest balanced accuracy for both mortality (95.45%) and hospital stay (94.24%). Factors associated with worse outcomes of remdesivir use in terms of mortality included limitation of life support treatment, need for ventilatory support (especially invasive mechanical ventilation) on day 14 after the first dose of remdesivir, lymphopenia, low levels of albumin and hemoglobin, presence of flu and/or coinfection, and cough. Factors associated with worse outcomes of remdesivir use in terms of hospital stay included the number of doses of the COVID-19 vaccine, patchy lung density, bilateral pulmonary radiological status, number of comorbidities, oxygen therapy, troponin and lactate dehydrogenase levels, and asthenia. These findings highlight the effectiveness of XGB as a strong candidate for accurately categorizing COVID-19 patients undergoing remdesivir treatment.

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

(1) Background: Burnout syndrome results from chronic stress in the work-place. The COVID-19 pandemic has imposed a heavy workload on health professionals, doctors and nurses to respond to first-line health care during the first two years of an emergency caused by this virus. The aim of this study was to evaluate the prevalence of burnout in healthcare personnel, doctors and nurses during the COVID-19 pandemic. (2) Methods: This was a review of reviews on the prevalence of professional burnout syndrome in healthcare personnel, doctors and nurses before or during the COVID-19 pandemic, without language restrictions or missing data from the Cochrane Library electronic databases. In total, 48,657 articles were obtained from Pub-Med/MEDLINE and the Web of Science. (3) Results: After completing the examination, 20 articles were included in the review. Of these articles, 7% included nurses in their study population, 72% interviewed doctors from different specialties, and the remaining 21% reported personnel data. Healthcare as a whole: In total, 624 articles with 233,087 participants were included. Regarding the prevalence by subscale, a PD of 33% (95% CI; 33%- 34%), an AE of 37% (95% CI; 37%- 37%) and a PR of 29% (95% CI) were found. %; 29% and 29%). ; (4) Conclusions: The incidences of DP and AE are high, and that of RP is low. These findings demonstrate the high prevalence of burnout according to subscale. Burnout is a problem of great magnitude, and as such, interventions must be implemented immediately at the individual and group levels by institutions and health systems.

The Glasgow Declaration called for scientifically based measurements of CO2 emissions in the tourism industry to achieve the goals of the Paris Agreement. Despite the economic and employment downturn caused by COVID-19, there are limited cases of environmental assessments related to tourism. This study estimates the carbon footprint of the tourism industry in major G20 countries before and after COVID-19. Understanding the characteristics of inbound tourism and domestic tourism is important as they impact different markets. GHG emissions from tourism mainly stem from transportation, but the type of travel and country differences also make souvenirs, accommodation, and food and beverages significant emission factors. The pandemic has greatly impacted the tourism industry. In 2020, GHG emissions from both domestic and inbound tourism significantly decreased, affecting the number of tourists. In some countries, measures against COVID-19 influenced these figures, and although signs of recovery were observed in 2021, the reduction rates varied by country. These emission reductions should be the goals pursued by the tourism industry in the post-COVID-19 era, requiring efforts to achieve sustainable tourism.

Digital transformation has become a strategic priority for the enterprises, the public organizations, and the cities lately since it addresses the adoption of cutting-edge information and communication technologies (ICT) for optimizing their business processes and for generating new types of value to their end users. Although the Covid-19 pandemic is claimed to be over, it appears that organizations and cities changed their digital transformation strategies that had defined before the outbreak. The aim of this paper is to investigate the type of changes that were caused both to enterprises and cities due to the pandemic. It investigates whether and in which directions it caused business changes and how the smart city strategic objectives were affected due to pandemic, especially in cases where digital transformation strategies were defined before the outbreak. This study uses bibliometric analysis to determine the effects of Covid-19 on businesses and cities. Findings specify strategic changes and important trends, like the migration of the production supply chains to nearby territories. Moreover, this article utilizes the European Intelligent Cities Challenge initiative, in which cities had defined their priorities for their digital transformation before the outbreak. From the analysis of the strategic plans of the involved cities, it is attempted to determine whether, which cities and in which directions they changed their strategies due to the pandemic.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflamation and to explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. The study included 139 patients who were enrolled between January-June 2021, mean age 46.7±15.2 years, 68 were men, 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work up, lab. analyses, cardiac ultrasound, and CMR on 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE, (4.3±0.23 vs 3.2±0.14g/L, p<0.05; respectively), as well as D-dimer (1.8±0.3 vs 0.8±0.1 mg/L FEU). Also troponin was statistically significantly higher in patients with myocardial LGE (13.1±0.4ng/L) compared to those with normal myocardium (4.9±0.3ng/L, p<0.001). We demonstrated chest pain, fatigue and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.

Type II pneumocytes are the target of SARS-CoV-2 which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. Here we evaluated whether the treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2–), lipid peroxidation (LPO), and thiols groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), -S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There was a significant increase in LPO and carbonyls (p≤0.03) and a decrease in TAC, NO2–, thiols, GSH, (p&lt;0.001) in COVID-19 patients. The activities of the ecSOD, TrxR, GPx, GST, GR and peroxidases were decreased (p≤ 0.04). The treatment with MT favored the activity of the antioxidant enzymes which contributed to increase TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis functioning as a glycolytic agent and inhibited the Warburg effect. Thus, MT restores the redox homeostasis which is altered in COVID-19 patients and can be used as adjuvant therapy in the SARS-CoV-2 infection.

Marginalised families faced significant challenges during the COVID-19 pandemic. This study explores inequalities in Japanese mothers’ and children’s health and wellbeing and family economic stability before and during the pandemic. Data sources were: nationwide surveys in 2019 and 2021 of families with children using medical institutions across Japan; infant mortality and adolescent suicide rates between 2018 and 2021 from publicly available sources. Outcomes by poor and non-poor families were compared for 2019 and 2021 using simple descriptive statistics. Poor mothers' part-time working increased from 41% to 61% and regular employment was reduced by two-thirds. Well-being of poor mothers worsened from 39% to 55%. Employment opportunities and wellbeing did not change for non-poor mothers. School subsidies among poor families increased from 23% to 55%. The infant mortality rate (IMR) among unemployed families increased significantly from 12.9/1,000 to 18.2/1,000 between 2018 and 2021 compared with a decreasing overall IMR from 1.9/1000 to 1.7/1000. Suicide rates in 10-19 year olds increased over the same period although no socio-economic indicators were available. Inequalities in mothers’ and children’s health and well-being indicators and family economics increased between 2019 to 2021 in Japan. This study cannot attribute cause but suggests a possible role of the pandemic.

The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human wild-type virus. The samples were then incubated with cells expressing the ACE2 receptor and therefore very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, to completely inhibit SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in the in vivo skin model. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of COVID-19 disease.

Objective: Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection (“hybrid immunity”). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan.Methods: We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization.Results: The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately one year after coronavirus disease 2019 (COVID-19 diagnosis), even without booster vaccination.Conclusions: Most Japanese patients naturally infected with COVID-19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid-immunized cases is highly questionable regarding cost-effectiveness and risk-benefit.

Customer satisfaction is the process of reaching a customer's expectations to generate delightful experiences with a product or a brand. Delight involves delivering an unforgettable experience to users by focusing on their requirements, desires, and interests. Delighting Customers is crucial for organizations’ economic growth worldwide, especially in the airline industry. This study aims to determine if safety measures, ticketing policies, and the cost of air travel impact among the airline passengers’ satisfaction post-COVID-19 in Malaysia. A research framework is designed to present an in-depth understanding of the mentioned variables. In this study, a comprehensive survey using online questionnaire was used and 388 valid responses were obtained from airline passengers in Malaysia. Data were analyzed by employing data reduction technique and multivariate data analysis. The results revealed that safety appears to be the most essential aspect of airline customer satisfaction among Malaysians, while cost is perceived as a significant factor. Moreover, as the cost of living rose because of the pandemic, many of the income earners in the lower category are less inclined to take vacations. In a nutshell, the study recommends that airlines implement a conscious practice that contributes to the happiness of passengers, which in turn increases profitability and ensures sustainable growth of the airlines.

The present paper presents findings from the follow-up of 185 of these nurses who had been involved in the front-line care of COVID-19 patients in urban centres in Northern England, during and after the “second wave” of COVID patients in November, 2020. Measures of adjustment, stress (including PTSD), and Maslowian self-actualization were added to earlier measures of personality, adjustment, work-life stress, and career intention. Cluster analysis identified three types in the 2020-2023 cohort: I ‘Actualizing Professionals’; (N=62); II ‘Strong Professionals’ (N=56); III ‘Highly Stressed Nurses’ (N=45). These latter very stressed nurses included all nurses (N=16) identified as having PTSD symptoms.

The Covid-19 crisis has been one of the most relevant economic shocks in the history of the modern economy, mainly due to the restrictions on travel and social interaction taken by the authorities (quarantines, closure of schools, artistic activities, bars, and restaurants, capacity in stores), to reduce the transmission of the virus (Sars-Cov2), having consequences on the national productions of all countries (about 7% for the loss of GDP worldwide). In our study, we analyze, through clustering methods, the effects of the level of contagion, economic projections, and economic mitigation measures taken by governments for managing the pandemic. According to the analyses, it can be concluded that a low infection rate implies a lower loss of product and economic savings when applying economic mitigation measures, taking relevance in the management of sanitary measures to reduce the transmission of the virus (and the temporality of these).

As the COVID-19 pandemic has caused enormous damage to society, economy and public health security, it is crucial to combat the epidemic and allocate social and health resources effectively. Global optimization algorithms are extensively used in many domains to find optimal solutions to complex problems. Thus, a survey of three typical global optimizations applied on the COVID-19 pandemic is timely. This article is structured into three typical global optimization algorithms - Genetic Algorithm, Particle Swarm Optimization, and Cat Swarm Optimization - and summarizes the framework models and practical applications, as well as other optimization methods that may be applied to COVID-19. Finally, current unresolved challenges and future research opportunities to be explored are summarized.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

Background: The potential impact of the pandemic on mental health should not be overlooked, especially among vulnerable populations such as women who gave birth during the COVID-19 pandemic. The aim of the study was to assess the mental health status of women who gave birth during a pandemic and to examine the possible links between the onset of depressive disorder symptoms in close proximity to the time of delivery and the socio-demographic conditions, health status and obstetric circumstances of the patients. Materials and Methods: The study is a cross-sectional survey conducted from 01.03.2020 to 01.03.2023, during the period of SARS-CoV-2 (COVID-19) pandemic, based on a retrospective evaluation of 860 postpartum women. The screening tool used to assess symptoms of postpartum depression was the Edinburgh Postnatal Depression Rating Scale (EPDS) questionnaire. The questionnaire was completed both in the Obstetrics and Gynaecology Clinical Sections I and II of the "Pius Brînzeu" County Emergency Hospital from Timisoara, Romania and online using Google Forms. Results: The highest severity of postpartum depression symptoms was observed during the COVID-19 pandemic. The results of the study conducted during the period of SARS-CoV-2 pandemic (COVID-19) showed that the prevalence of major postpartum depressive disorder (EPDS ≥ 13) was 54.2% (466 patients), while 15.6% (134) had minor depressive disorder (10 &lt; EPDS ≤ 12) in the first year after delivery. Comparing these results with those obtained in research conducted before the onset of the pandemic period shows an alarming increase in the prevalence of postpartum depression. Risk factors associated with postpartum depression included type of delivery, level of education, socio-economic conditions, health status, age, background, personal obstetric history (number of abortions on demand, parity). Conclusions: The effects of the pandemic on mental health are of particular concern for women in the first year after childbirth. Observing these challenges and developing effective measures to prepare our health system early can help and facilitate effective mental health screening for postpartum women, promoting maternal and child health.

Sepsis is a life-threatening condition caused by the body's overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which ranks among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection was frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. These data indicate similarity and interdependences of both syndromes, but also significant differences which will be discussed in the present review.

At the beginning of 2020, with the onset of the pandemic, the traditional learning environment for learners drastically changed globally. Since then, most students/teachers have started and practiced distance and virtual learning/teaching. Thus, a technological breakthrough in virtual learning has followed. In connection with this, many countries worldwide have commenced allocating additional financing and funds for educational institutions' technological improvement and development. The long-term stay in distance learning has revealed and highlighted new problems students face: their knowledge level has decreased, they lack socialization skills, and they face psychological and physical health problems. Due to this negative impact on students, a need to research and evaluate how much the EU countries allocated to solve the distance learning-caused problems and what programs or models they prepared has emerged and encouraged further studies. The research has found that many countries increased their allocations very minimally, e.g., 0.0.1%, but some increased their available budgets to 32%. Notably, most countries did not separate distance learning exit funding from distance learning preparation funding. Based on the problems the countries saw, only a few states identified withdrawal from distance learning as a problem. Considering this, we set ourselves the goal to evaluate exit models from distance learning and allocated funding amounts. The following objectives were planned to achieve the goal: · to evaluate the global practice of exit from distance learning; · to determine the scope of funding for pandemic management; · to evaluate the amounts of funding allocated to manage pandemic-caused consequences and the GDP ratio. Research methods: mathematical-statistical analysis, empirical analysis, and analysis of scientific literature.

COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-a. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IkBa was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF-a levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIkBa in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.

In bioinformatics research, traditional machine learning methods have demonstrated efficacy in addressing Euclidean data. However, real-world data often encompasses non-Euclidean forms, such as graph data, which contain intricate structural patterns or high-order relationships that elude conventional machine-learning approaches. Representation learning seeks to derive valuable data representations from enhancing predictive or analytic tasks, capturing vital patterns and structures. This method has proven particularly beneficial in bioinformatics and biomedicine, as it effectively handles high-dimensional, sparse data, detects complex biological patterns, and optimizes predictive performance. In recent years, graph representation learning has become a popular research direction. It embeds graphs into a low-dimensional space while preserving the structural and attribute information of the graph, enabling better feature extraction for downstream tasks. This study extensively reviews representation learning advancements, particularly in the research of representation methods since the emergence of COVID-19. We begin with an analysis and classification of neural network-based language model representation learning techniques as well as graph representation learning methods. Subsequently, we explore their methodological innovations in the context of COVID-19, with a focus on the domains of drugs, public health, and healthcare. Furthermore, we discuss the challenges and opportunities associated with graph representation learning. This comprehensive review presents invaluable insights for researchers as it documents the development of COVID-19 and offers experiential lessons to preempt future infectious diseases. Moreover, this study guides future bioinformatics and biomedicine research methodologies.

Frontal Temporal Dementia (FTD) is a neurological disorder known to have less therapeutic options. So far only a few biomarkers are available for FTD that can be used as potential comorbidity targets. To this end, in the present study we aim to identify potential biomarkers or susceptible genes for FTD that show comorbidities with diseases such as COVID-19 and Breast Cancer. Gene expression Omnibus datasets containing FTD expression profiles from African American and white ethnicity background were included in our study. In FTD samples of GSE193391 dataset, we identified 305 DEGs with 168 genes being up-regulated and 137 genes being down-regulated. We conducted comorbidity analysis for COVID-19 and Breast cancer followed by analysis of potential drug interactions, pathogenicity, analysis of genetic variants and functional enrichment analysis. Resulting genes AKT3, GFAP, ADCYAP1R1, VDAC1, and C4A showed significant transcriptomic alterations in FTD and significant comorbidity status with COVID-19 and Breast cancer. Functional pathway analysis revealed that these comorbid genes were significantly enriched in the pathways such as glioma, JAK/STAT signaling, systematic lupus erythematosus, neurodegeneration-multiple diseases and neuroactive ligand-receptor interaction. Overall, from these results, we concluded that these genes could be recommended as potential therapeutic targets for the treatment of comorbidities in FTD.

The COVID-19 virus is spread to the respiratory system by minute airborne particles in contrast to large particle fomite transmission. Yet, an often-repeated health directive during the COVID-19 pandemic was to improve handwashing to limit the spread of the virus. Persistent handwashing can aggravate obsessive-compulsive disorder (OCD), diminishing mental health. Given that handwashing is unlikely to control the spread of COVID-19, it is pertinent to determine if the directive for handwashing to eradicate the COVID-19 virus increased the incidence of OCD and, as such, promoted negative mental health. This scoping review of the parameter, “handwashing, mental health, COVID-19, OCD”, conducted during July 2023, searched six relevant databases. The result was that negative mental health related to increased handwashing was evident both for those already diagnosed with OCD and regarding new cases of OCD throughout the duration of the pandemic. The conclusion is that health officials should update details of their health directives as information becomes available during a pandemic and, concerning COVID-19, the directive to concentrate on handwashing should have been relaxed once it was known that spread of the virus by fomite transmission was improbable. This likely would have reduced the incidence of OCD and improved mental health.

As a result of the COVID 19 outbreak that has affected the whole world, teacher leadership has gained more significance. Teacher leadership is a multidimensional concept. While some teachers exercise leadership only at the classroom level, others exercise leadership at macro level. This level of leadership enactment is directly related to how teachers construct their professional identity in relation to leadership. This study aims to explore the leadership-related professional identities of teachers who came to the fore especially during the COVID 19 pandemic period by using the latent profile analysis method. The data were collected a sample of 710 teachers. Teachers completed Teacher Leadership Behavior Scale that measures teacher leadership behaviors at four levels: classroom, parental, micro-level, macro-level. Participants also completed Rosenberg Self-Esteem Scale, Teacher Self-Efficacy Scale, Openness to Authority Scale, and Job Satisfaction Scale. As a result of latent profile analysis, three distinct profiles of teacher leadership identity emerged: those who exercise leadership at a minimum level, an intermediate level and a maximum level across all four levels of teacher leadership. These profiles were labeled as "extended professionality," "intermediate professionality," and "restricted professionality," drawing upon Hoyle's (1974) conceptualization of teacher professional identity. These findings suggest that teachers construct their identity differently about teacher leadership. It is essential for school leaders to first explore those different levels of professional identity and tailor their professional development activities accordingly.

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211 and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data supports the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708 and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

The Main Protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

The SARS-CoV-2 virus, causative agent of COVID-19, is known for its genetic diversity. Virus variants of concern (VOCs) as well as variants of interest (VOIs) are classified by the World Health Organization (WHO) according to their potential risk to global health. This study seeks to enhance the identification and classification of such variants by developing a novel bioinformatics criterion centered on the virus's spike protein (SP1), a key player in host cell entry, immune response, and a mutational hotspot. To achieve this, we pioneered a unique phylogenetic algorithm which calculates EIIP-entropy as a distance measure based on the distribution of the Electron-Ion Interaction Potential (EIIP) of amino acids in SP1. This method offers a comprehensive, scalable, and rapid approach to analyze large genomic data sets and predict the impact of specific mutations. This innovative approach provides a robust tool for classifying emergent SARS-CoV-2 variants into potential VOCs or VOIs. It could significantly augment surveillance efforts and understanding of variant characteristics, while also offering potential applicability to the analysis and classification of other emerging viral pathogens and enhancing global readiness against emerging and re-emerging viral pathogens.

Background: COVID-19 pneumonia caused by SARS-Cov-2 virus induces alveolar collapse and hypoxia that may become severe. The aim of the study is to analyze the effects of chest physiotherapy using a threshold valve in patients with acute respiratory failure due to COVID-19 pneumonia. Methods; Retrospective observational study, in hospitalized patients from March to May 2020. Breathing exercises were performed with a threshold valve of 10 cmH2O. Fraction of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the first session and at the end of the 5th day of chest physiotherapy treatment. Results: The final sample included 125 patients. Significant differences (p&lt;0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250±88.4 vs 275.6±97.5, p&lt;0.001), reaching 354.4±110.2 after 5 days of therapy (p&lt;0.001 with respect to baseline). Mean baseline respiratory, heart rate and level of dyspnea measure by the Borg scale did not change during the technique performance. In patient maneuvers with FiO2&gt;0.4, the SaO2/FiO2 ratio increase was higher than in patients with milder severity (46.85 ± 77.69, p&lt;0.01). Conclusions: Chest physiotherapy with a 10 cmH2O threshold valve is a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

The COVID-19 pandemic has raised questions about indirect impact in pregnant women on the development of their future children. Investigating the characteristics of lipid metabolism in the "mother-placenta-fetus" system can give information about the pathophysiology of COVID-19 infection during pregnancy. 234 women were included in study. Maternal plasma, cord blood, amniotic fluid lipidome were analyzed using HPLC-MS/MS. Differences in lipid profile were searched by Manna-Whitney and Kruskall-Wallis test, diagnostic model based on logistic regres-sion were bilt by AIC. Elevation levels of lysophospholipids, triglycerides, sphingomyelins, and oxidized lipids was registered in patients’ after COVID-19 maternal and cord plasma. An increase in maternal plasma sphingomyelins and oxidized lipids was observed in cases of infection during the second trimester. In amniotic fluid, compared to the control group, nine lipids are reduced, six lipids are elevated. Levels of phosphoglycerides, lysophosphoglycerides, and phosphatidylinosi-tols decreased during infection in the second and third trimesters of pregnancy. Newborn’s health diagnostic model based on maternal plasma were developed for each group and exhibit good di-agnostic value (AUC> 0.85). Maternal and cord plasma’s lipidome changes during delivery, asso-ciated with Covid-19 infection during pregnancy, are synergistic. The most significant disturbances occur with infections in the second trimester of pregnancy.

The documentation and management of the cultural heritage of the COVID-19 pandemic as well as the heritage digital age are emerging discourses in cultural heritage management. The enthusiastic uptake of a generative artificial intelligence application (ChatGPT) by the general public and academics alike has provided an opportunity to explore i) whether, and to what extent, generative AI can conceptualize an emergent, not well-described field of cultural heritage (the heritage of COVID-19, ii), whether it can design an exhibition on the topic and iii) whether it can identify sites associated with the pandemic that may be(come) significant heritage. Drawing on an extended ‘conversation’ with ChatGPT, this paper shows that generative AI is capable of not only developing a concept for an exhibition of the heritage of COVID-19 but also that it can provide a defensible array of exhibition topics as well as a relevant selection of exhibition objects. ChatGPT is also capable of making suggestions on the selection of cultural heritage sites associated with the pandemic, but these lack specificity. The discrepancy between ChatGPT’s responses to the exhibition concept and its responses regarding potential heritage sites suggests differential selection and access to data that were used to train the model, with a seemingly heavy reliance on Wikipedia. The ‘conversation’ has shown that ChatGPT can serve as a brainstorming tool, but that a curator’s considered interpretation of the responses is still essential.

The South African government introduced a nationwide lockdown in March 2020 to mitigate the spread of Covid-19. Among other restrictions, the government banned the sale of tobacco products, which lasted for nearly five months. We performed a Google search using the keywords smok*, puff*, lockdown, tobacco, and cigarette*, for articles published in English from 23 March 2020to 18 December 2020 and analysed 441 online media articles. We identified the main arguments made by proponents and opponents of the tobacco sales ban, which were categorised into themes. Three themes were prominent: medical, legal, and economic/financial. Legal aspects were covered in 48% of articles, followed by economic (34%), and medical aspects (18%). The media was generally ambivalent about the tobacco sales ban during the first five weeks of lockdown. Sentiment then turned against the ban. because the medical rationale was not well communicated by the government, there was limited empirical evidence of a link between smoking and contracting Covid-19, and the sales ban was ineffective, since most smokers still purchased cigarettes. Policy framing in the media plays an important role in how the public receives the policy. Any future tobacco control policy intervention should be well-considered and appropriate cessation support services offered.

(1) Background: COVID-19 had devastating effects on both physical and mental well-being, prompting the need for interventions. This study aimed to explore the impact of mindfulness-based stress reduction on mental health, mindfulness, and sleep disorders in COVID-19 survivors.; (2) Methods: In this interventional parallel study, the sample was selected university students in nursing and midwifery faculties using total population sampling. The intervention included providing counseling on mindfulness methods by trained experts. General health, mindfulness and sleep quality questionnaires were used for data collection. Data were analyzed using SPSS22, descriptive and interferential statistic. A significance level of 0.05 was considered; (3) Results: In this study, the mean age of the students was 20.29 ± 2.03 years. 69.5% of the participants were female and 96% were single. 71.3% were studying nursing and 67% had a history of Corona infection. The intervention was only effective on general health questionnaire and the mean score of this questionnaire was 1.7 higher than the control group; (4) Conclusions: the study indicated that MBSR intervention improves mindfulness, mental health, and sleep quality in COVID-19 survivors. Regular assessment and use of this intervention can help address long-term challenges and improve overall well-being.

The lockdown implemented to tackle the spread of the COVID-19 pandemic had a positive impact on air quality. Globally, studies have shown that the air pollutants levels reduced temporally during the restriction measures. In this study, we evaluated the impact of COVID-19 restrictions on the air quality of Western Macedonia, Greece, using the hourly concentrations of PM2.5 and PM10 along with meteorological data from the Air Quality Monitoring Stations (AQMS) operated by the Lignite Center of Western Macedonia. In Western Macedonia, previous studies have identified that there is a general reduction in air pollutants levels during the last decade due to coal phase-out plan for power generation. During the lockdown the levels of PM2.5 and PM10 decreased further. However, reduced emissions from the local mining activities and lignite-fired power plant electricity generation, as well as the weather conditions seems to contribute to improving air quality.

U.S. Spanish-speaking populations experienced gaps in timely COVID-19 information during the pandemic and disproportionate misinformation exposure. Brigada Digital de Salud was established to address these gaps with culturally-tailored, Spanish-language COVID-19 information on social media. From May 1, 2021-April 30, 2023, 495 Twitter, 275 Facebook, and 254 Instagram posts were published and amplified by 10 trained community health workers. A qualitative content analysis was performed to characterize topics and formats of 251 posts. To assess reach and engagement, page analytics and advertising metrics for 287 posts were examined. Posts predominantly addressed vaccination (49.45%), infection risks (19.12%), and COVID-related scientific concepts (12.84%). Posts were educational (48.14%), and aimed to engage audiences (23.67%), promote resources (12.76%), and debunk misinformation (9.04%). Formats included images/text (55.40%), carousels (27.50%), and videos (17.10%). By June 9, 2023, 394 Facebook, 419 Instagram, and 228 Twitter followers included mostly women aged 24-54. Brigada Digital reached 386,910 people with 552,037 impressions and 96,868 engagements, including 11,292 likes, 15,240 comments/replies, 9,718 shares/retweets, and 45,381 video play-throughs. The most engaging posts included videos, trending topics, and music or audio-narration. This community-based model to engage Spanish-speaking audiences on social media with culturally-aligned content to counter misinformation shows promise for addressing public health threats.

Suffocation syndrome is the leading cause of hypoxia and mortality in the most common lung diseases, asthma and COVID-19. Inhaled corticosteroids (ICSs) have been shown to be the main-stay of critical care in these diseases. Meanwhile, mortality from strangulated hypoxia is highest in low-income countries because ICSs are not currently available to many patients. Warm alkaline hydrogen peroxide solutions (WAHPSs) have reportedly been invented in recent years to urgently turn thick sputum, mucus, pus, serous fluid, blood clots and many other biological masses con-taining the enzyme catalase into a fluffy oxygenated foam. It has been shown that the mechanism of action of WAHPSs consists in alkaline saponification of lipid and protein-lipid complexes of bi-ological masses and their transformation into oxygen foam, because hydrogen peroxide is urgently decomposed into water and oxygen gas under the action of the biological masses catalase enzyme At that excess oxygen is absorbed into blood through lungs and increases blood oxygen saturation. Based on the described mechanism of action of WAHPSs and the high availability of their ingre-dients, it is suggested that mortality from choking and hypoxia in asthma and COVID-19 can be reduced by combining ICSs with inhaled WAHPSs, especially in poor countries. The essence of the inventions underlying the formation of WAHPSs is given.

The emergence of new SARSCoV-2 variants can affect vaccine efficacy, laboratory diagnosis and therapies already available, triggering interest in the search for antiviral agents for SARSCoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARSCoV-2. Methods. This retrospective study evaluated the dynamic and viral clearance of SARSCoV-2 in hospitalized adult participants (PTs) with COVID-19 pneumonia who received RBV aerosol within a compassionate use study. Was also assessed the impact of RBV on the clinical outcome and the mutational profile of SARSCoV-2. Results. The median RNA values measured in nine PTs included in the study de-creased from baseline to discharge (at BL, threshold cycle (Ct)=22.4, IQR 19.84-5.07; at discharge, Ct=27.92, IQR 26.43-36.11). Seven/9 PTs experienced a clinical improvement, while two PTs deceased during hos-pitalization. In PTs with a favorable outcome the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within day 14th from discharge. A mutational pattern after RBV was detected in 3/5 PTs in whom was available whole genome sequencing. Conclusions. RBV may limit SARSCOV-2 replication resulting in a favorable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARSCoV-2.

The offshore oil and gas working environment is an inherently dangerous one, with risks posed to physical safety on a daily basis. One neglected field of research is the added psychosocial stressors present in this environment. This research examined the experiences of offshore oil and gas workers through one-on-one online interviews which were recorded and transcribed. Transcripts were analysed through qualitative software NVivo, which generated themes and patterns for the responses given to questions which were developed through a focus group. The results of the analysis showed that multiple psychosocial stressors are present for this population, such as fear of speaking up, unsatisfactory company-provided facilities, work-life interference, work status, micromanaging, gender harassment and bullying. In addition, interviews identified that production and time pressures along with fatigue can influence accidents and mistakes. Climate factors also cause discomfort, however these are managed according to best practice by organisations. Due to the timing of the study, COVID-19 was a significant stressor for some, but not all, employees. In conclusion, offshore oil and gas workers face multiple stressors in a dangerous environment that may lead to devastating consequences.

Hospital readmission and length of stay prediction provide info to manage hospitals’ bed capacity and the number of required staff, especially during pandemics. We present a hybrid deep model called Genetic Algorithm-Optimized Convolutional Neural Network (GAOCNN) with a unique preprocessing method to predict hospital readmission and the length of stay in patients having various conditions. GAOCNN uses one-dimensional convolutional layers to predict hospital readmission and length of stay. The parameters of the layers are optimized using a genetic algorithm. To show the performance of the proposed model in patients with various conditions, we evaluate the model under three healthcare datasets; the Diabetes 130-US hospitals dataset, the COVID-19 dataset, and the MIMIC-III dataset. The diabetes 130-US hospitals dataset has information on both readmission and the length of stay, while COVID-19 and MIMIC-III datasets just include information on the length of stay. Experimental results show that the proposed model’s accuracy for hospital readmission is 97.2% for diabetic patients. Also, the accuracy of the length of stay prediction is 89%, 99.4%, and 94.1% for diabetic, COVID-19, and ICU patients, respectively. These results confirm the superiority of the proposed model compared to existing methods. Our findings offer a platform for managing healthcare funds and resources for patients with various diseases.

Purpose The COVID-19 pandemic, triggered by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in over 160 million infections and 3.5 million fatalities worldwide. Evidence of SARS-CoV-2 presence in the highly vascularized penile tissue and the established correlation between COVID-19 and subsequent erectile dysfunction (ED) has emerged. Robot-assisted radical prostatectomy (RARP) is a popular procedure for prostate cancer because of its reliability and swift recovery rate. However, the ED prevalence post-surgery is believed to be comparable to open surgery, and postoperative ED significantly affects the patient's quality of life. Our study aimed to explore the effect of COVID-19 on ED recovery in patients undergoing bilateral nerve preservation during RARP. Materials and Methods We conducted a retrospective study on 85 patients who underwent bilateral nerve-sparing RARP (nsRARP) at our institution between December 2017 and May 2021. Chart reviews and the International Index of Erectile Function-5 (IIEF-5) questionnaire facilitated the analysis. Our objective was to contrast ED recovery after surgery between SARS-CoV-2–infected and non-infected patients using preoperative IIEF-5 scores and scores at 6, 12, and 24 months post-surgery. We defined successful ED recovery as an IIEF-5 score of 17 or higher and successful sexual intercourse. We also compared ED recovery rates between the two groups, regardless of the timing of COVID-19 diagnosis. IBM's SPSS version 18.0 assisted in the statistical analysis, with Fisher's exact test and chi-square test used for comparing categorical variables. Independent t-tests determined mean differences between baseline and postoperative IIEF-5 scores. A p-value less than 0.05 was considered statistically significant. Results From December 2017 to May 2021, our institution executed 213 RARP cases, with 185 of these involving nerve preservation. Among these patients, 133 had an IIEF-5 score of 17 or higher during preoperative EF assessment. We included 85 patients with consistent IIEF-5 records before surgery and at 6, 12, and 24 months post-surgery in this study. Of these, 44 and 41 patients comprised the COVID-19–positive and COVID-19–negative groups, respectively. The COVID-19–positive group had a higher proportion of diabetes mellitus (DM) patients (24 (54.55%) vs. 7 (17.07%), p<0.001). There was no significant difference in preoperative IIEF-5 scores or scores up to 6 months after surgery between the two groups. However, the IIEF-5 scores of the COVID-19–positive group were statistically lower after 12 and 24 months post-surgery. Additionally, the COVID-19–negative group showed a more considerable score increase between 6 and 12 months post-surgery, and the EF recovery rate was lower in the COVID-19–positive group starting from the 12th month after surgery. Within the COVID-19–positive group, no statistically significant difference in IIEF-5 scores was found between single infection and multiple reinfection groups. Conclusions Principal component analysis revealed the impact of COVID-19 on ED recovery in patients who underwent nsRARP. The most substantial changes in IIEF-5 scores occurred between 6 and 12 months. From 12 months onwards, the COVID-19–positive group had significantly lower scores, and fewer patients had IIEF-5 scores above 17. However, the number of COVID-19 diagnoses did not significantly affect the IIEF-5 scores.

The Covid-19 pandemic has produced a change in the way of living, socializing and a modification in Health Systems around the world. A multicentre retrospective study was carried out to study orofacial trauma in one of the regions most affected during the first wave of the pandemic, with the participation of the five main tertiary hospitals in Madrid. The aim of this study is to evaluate the epidemiology of orofacial surgical trauma during the 1 year of COVID pandemic and compared to de prior year. Age, sex, mechanism, localization, and treatment were studied. P-value <0.05 was considered statically significative. Reduction of 39.36% (<0.001) in maxillofacial fractures was observed, without significance change in sex, localization or treatment. Significant increase in age (35,92 vs. 40,26) (p = 0.006) was observed. Significant decline in mechanism was noted (p = 0.025), decreasing personal violence (41% vs 35%) and sports (14% vs 8%); increasing in falls (27% vs 35%), precipitation (2 vs 5%), and traffic accidents (12% vs 13%). The mandible was the most frequent fractured bone. The COVID pandemic has produced epidemiological variations in orofacial trauma, making it necessary to monitor social and legal changes that may require reorganization to adjust to population needs.

Work done by us shows that rough topology is a good tool for dealing with things that happen in the real world. The concept of ”basis” has been used to show out the deciding elements of the recent outbreak of COVID-19 that was reported all over the world.