Dispersal history of SARS-CoV-2 in Galicia, Spain (preprint)

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Protocol for primary human lung organoid-derived air-liquid interface in vitro model to study response to SARS-CoV-2 (preprint)

This article presents a comprehensive protocol for establishing primary human lung organoid-derived air-liquid interface (ALI) cultures from cryopreserved human lung tissue. These cultures serve as a physiologically relevant model to study human airway epithelium in vitro. The protocol encompasses lung tissue cryostorage, tissue dissociation, lung epithelial organoid generation, and ALI culture differentiation. It also demonstrates SARS-CoV-2 infection in these cultures as an example of their utility. Quality control steps, ALI characterization, and technical readouts for monitoring virus response are included in the study. For additional details on the use and execution of this protocol, please refer to Diana Cadena Castaneda et al. (https://doi.org/10.1016/j.isci.2023.107374).

Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian Hamsters (preprint)

Hybrid immunity to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses.

Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia (preprint)

The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression towards severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection. The infection measured by nucleoprotein expression, was a late event appearing between day 4-6 post infection for Wuhan-like virus. Other variants demonstrated increasingly accelerated timelines of infection. All variants triggered similar transcriptional signatures, an early inflammatory/immune signature preceding a late type I/III IFN, but differences in the quality and kinetics were found, consistent with the timing of nucleoprotein expression. Response to virus was spatially organized: CSF3 expression in basal cells and CCL20 in apical cells. Thus, SARS-CoV-2 virus triggers specific responses modulated over time to engage different arms of immune response.

Relationship Between Psychological Distress, Burnout and Work Engagement in Workers During the COVID-19 Pandemic: A Systematic Review

Objective: The psychological distress that the COVID-19 pandemic has produced has generated negative effects on workers, and in one way or another this has affected their work engagement within companies. The aim of this research was to assess the relationship between psychological distress, burnout and work engagement in workers during the COVID-19 pandemic. Methods: A systematic review was carried out following the PRISMA methodology, taking articles from the Scopus, Pubmed, and Web of Science databases from the beginning of the pandemic until November 2022. The methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for non-randomised studies. Results: 24 articles were selected. All the articles found an association between psychological distress, burnout or other factors and work engagement. Conclusion: The COVID-19 pandemic has had an impact on work engagement and a negative relationship with psychological distress and burnout, hence the importance of companies taking measures to minimise levels of psychological distress and burnout.

Impact of COVID-19 pandemic on cardiometabolic patients without SARS-CoV-2 infection in Latin America

A cross-sectional survey including 38 questions about demography, clinical condition, changes in health habits, and medical treatments for cardiometabolic patients in outpatient follow-up was conducted. From June 15 to July 15, 2020, a total of 13 Latin-American countries participated in enrolling patients. These countries were divided into 3 geographic regions: Region 1 including North, Central, and Caribbean Regions (NCCR), Region 2 including the Andean Region (AR), and Region 3 including the Southern Cone Region (SCR). 4.216 patients were analyzed, resulting in a coefficient of 33.82%, 32.23%, and 33.94% for NCCR, AR, and SCR, respectively. Significant differences were found between the AR, SCR, and NCCR regions. The analysis of habitual medication usage showed that discontinued use of medication was more present in AR, reaching almost 30% (p < 0.001). The main finding of this study was the negative impact that restrictive measures have on adherence to medications and physical activity: Rs = 0.84 (p = 0.0003) and Rs = 0.61 (p = 0.0032), respectively. AR was the most vulnerable region. Restrictive quarantine measures imposed by the different countries showed a positive correlation with medication discontinuation and a negative correlation with physical activity levels in patients analyzed. These findings characterize the impact of the consequences left by this pandemic. Undoubtedly, restrictive measures have been and will continue to have reverberating negative effects in most Latin-American countries.

Covid-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study

BACKGROUND AND AIMS To our knowledge, the psychological impact of coronavirus disease (COVID-19) vaccination has not yet been evaluated for the general population nor for chronic kidney disease (CKD) patients. The purpose of the study is to analyse the impact of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on anxiety and depression scores in patients with different modalities of CKD. METHOD A total of 117 renal patients (50 haemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants and 22 advanced CKD patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL) and perceived fears and resources with standardized (The Hospital Anxiety and Depression Scale;HADS) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. RESULTS The main finding of the study is that there is a decrease in the global mean of normal scores for anxiety and depression symptoms in CKD patients, post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine and lack of information. CONCLUSION These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.

Renal Recovery After Acute Kidney Injury Associated to COVID Requiring CRRT During ICU Hospitalization

BACKGROUND AND AIMS Renal recovery (RR) after AKI is a determinant outcome of future comorbidity and mortality in critical care patients. Related predictive factors remain uncertain. METHOD We retrospectively analyzed patients admitted to ICU between January 2020 and February 2021 from our critical nephrology database. We analyzed adult patients with diagnosis of AKI (KDIGO criteria) treated with renal replacement therapy (RRT) during ICU hospitalization. We excluded patients with dialysis support previous to the admission. The main outcomes we evaluated were (1) RR (successful suspension of RRT without hyperkalemia, increase in serum creatinine (SCr), hypervolemia or acidemia after 1 week without RRT, with urine volume > 500 mL/d without diuretic treatment or > 2000 mL/d with diuretics). (2) Mortality during hospitalization. RESULTS We found 1442 patients were admitted to ICU, 418 presented AKI (29.8%), of them, 178 patients (64% male) required RRT (AKI-RRTd) in ICU during follow-up, with mean age of 66 year old (52.8% >65 year). Main comorbidity and demographic data are in Table 1. Mean time in ICU was 19 days (RIC 11–35). The most frequent admission cause was non-surgical pathologies (93%), 53% of admitted patients had COVID-19 as main diagnosis (95 patients). There was need of vasoactive support in 73.6%, ventilatory support (82.6) and 67.2% of patients had fluid overload. The indication of dialysis was determined by a nephrologist: mainly oliguria, acidosis, hyperkalemia, fluid overload and increase SCr. Mean SCR at admission was 2.5 mg/dL. There were missing data in 48% of basal SCr (known SCr between 1 and 12 months prior to admission). Total mortality in AKI-RRTd was 70.8% (126 patients). In COVID patients, was 77.9% (74 patients). We found renal recovery in 63.4% of total survivors (33/52 patients). When analyzing COVID, there were 21 survivors, and we found renal recovery in 80.9% of patients. Patients who did not achieved renal recovery had longer ICU stay (median: 20 days, RIC: 4–26) and inhospitalization (median: 41 days, RIC: 29–58). Those patients were older, and had higher morbidity (diabetes), higher SCr at ICU admission and lower urine output. Their fluid balance was higher at 48 h after CRRT initiation (OR 3.05, 95% CI 1.39–6.65, P <.01). In COVID population without renal recovery, there were more urgent dialysis onset (OR 8.33, 95% confidence interval (95% CI) 1.04–66.2;P = .04), age > 65 year (OR 6.48, 95% CI 1.94–21.6;P < .01), positive fluid balance at 48 h after RRT (OR 3.25;95% CI 1.09–9.69;P = .03). The risk factors for mortality, were age > 65 year (OR 4.14, 95% CI 2.05–8.35;P < .01), mechanical ventilation (OR 3.28, 95% CI 1.48–7.30;P < .01), haemodynamic support (OR 4.37, 95% CI 2.14–8.92;P < .01). Otherwise, lower SCr at admission (OR 0.82, 95% CI 0.71–0.93;P < .01) and at instauration of RRT (OR 0.75, 95% CI 0.065–0.88;P < .01) were associated to lower mortality. In COVID patients, fluid overload at RRT initiation (OR 10.83, 95% CI 1.37–85.36;P = .02), age > 65 year old (OR 8.85, 95% CI 2.68–29.1;P < .01) and FiO2 > 50% at RRT start (OR 2.77, 95% CI 1.02–7.50;P = .04) were associated to higher mortality. CONCLUSION In ICU patients with AKI-RRT dependence, negative fluid balance at 48 h after RRT onset and in COVID patients, age < 65 year old, negative fluid balance at 48 h after RRT onset and non-urgent onset of RRT were related with renal recovery.

La intervención docente en educación física durante el periodo de cuarentena por COVID-19 (Teaching intervention in physical education during quarantine for COVID-19)

The aim of this study was to describe the changes in teaching intervention in Physical Education because of the quarantine caused by COVID-19. Data was collected from 191 active teachers by an online questionnaire, which consisted of 15 questions grouped into three main dimensions: contents reorganization, evaluation analysis and methodological changes. The main results of this study indicated that most of the teachers did not continue with the teaching hours prior quarantine. Regarding the evaluation, a high percentage of teachers neither planned it nor found it feasible. Contents of Physical condition and health were the most commonly used among teachers. Additionally, several difficulties were detected regarding the implementation of virtual teaching. Finally, the majority of teachers answered that quarantine could involve psychological and health problems for their students. These results could be considered for future research focused on Virtual Physical Education. Alternate : El objetivo de este estudio fue describir el cambio producido en la intervención docentes del profesorado de Educación Física como consecuencia de la cuarentena por COVID-19. Los datos de la investigación procedieron de una encuesta online realizada a 191 docentes en activo. La encuesta se compuso de 15 preguntas agrupadas en tres dimensiones principales, la reorganización de los contenidos, el análisis de la evaluación y los cambios metodológicos realizados. Los principales resultados del estudio indican que la mayoría de los docentes no han continuado con el horario de docencia previo a la cuarentena. La evaluación se destacó como la dimensión de mayor controversia, existiendo un alto porcentaje de docentes que no tenían previsto como evaluar e incluso no lo veían factible. El bloque de contenidos relacionado con la condición física y la salud fue el más utilizado por el profesorado. Adicionalmente, se describen una serie de dificultades detectadas con la implementación de la enseñanza virtual. Finalmente, la gran mayoría de encuestados consideró que la cuarentena ha podido suponer un problema psicológico y de salud a su alumnados. Estos resultados pueden servir de referencia para futuras investigaciones que se realicen relacionadas con la docencia virtual de la Educación Física.Alternate :Resumo. O objetivo deste estudo foi descrever as mudanças produzidas na intervenção docente de professores de Educação Física como consequência da quarentena do COVID-19. Os dados da pesquisa vieram de uma pesquisa online com 191 professores ativos. A pesquisa consistiu em 15 questões agrupadas em três dimensões principais, a reorganização do conteúdo, a análise da avaliação e as mudanças metodológicas realizadas. Os principais resultados do estudo indicam que a maioria dos professores não continuou com as horas de ensino anteriores à quarentena. A avaliação foi destacada como a dimensão de maior controvérsia, com um alto percentual de professores que não tinham planos de avaliar e que nem viam como viável. O bloco de conteúdo relacionado à condição física e saúde foi o mais utilizado pelos professores. Além disso, são descritas uma série de dificuldades detectadas com a implementação do ensino virtual. Finalmente, a grande maioria dos entrevistados considerou que a quarentena poderia representar um problema psicológico e de saúde para seus alunos. Esses resultados podem servir de referência para futuras pesquisas relacionadas ao ensino virtual da Educação Física.

COVID-19 VACCINATION IMPROVED PSYCHOLOGICAL DISTRESS (ANXIETY AND DEPRESSION SCORES) IN CHRONIC KIDNEY DISEASE PATIENTS: A PROSPECTIVE STUDY

BACKGROUND AND AIMS: To our knowledge, the psychological impact of coronavirus disease (COVID-19) vaccination has not yet been evaluated for the general population nor for chronic kidney disease (CKD) patients. The purpose of the study is to analyse the impact of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on anxiety and depression scores in patients with different modalities of CKD. METHOD: A total of 117 renal patients (50 haemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants and 22 advanced CKD patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL) and perceived fears and resources with standardized (The Hospital Anxiety and Depression Scale;HADS) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. RESULTS: The main finding of the study is that there is a decrease in the global mean of normal scores for anxiety and depression symptoms in CKD patients, postvaccination. We did not find statistically significant differences in depression or anxiety scores, nor HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine and lack of information. CONCLUSION: These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.

Facing Food Risk Perception: Influences of Confinement by SARS-CoV-2 Pandemic in Young Population.

A new food safety level of trust in food risk perception has been noticed, as a consequence of the SARS-CoV-2 pandemic. The pandemic made-up to review nutritional recommendations for the population, mainly for the young population. Here, the results of a designed survey for the young population, from the University of Valencia, Spain, belonging to grades in the health branch of knowledge, and in charge of carrying out the shopping task for their household, are reported. The study reports three different scenarios and years, as defined by the SARS-CoV-2 pandemic: before the pandemic (period January-December 2019), during the pandemic lockdown (period March 2020-August 2020), and after the pandemic lockdown (September 2020-June 2021). The survey was designed with questions, profiling responses using the best-worst elicitation (BWE) format. Results reported that trust and evaluation of information differed in all three scenarios. In the SARS-CoV-2 pandemic, there was (i) a high increase in trust in the information provided inside (by) the shopping place, while there were no changes for the outside (kept in medium score); (ii) trust in cooperative stakeholders went from a medium-low to medium-high score, while, for individual stakeholders, it was maintained as a medium score, and (iii) trust in information on food products was kept in high score. Regarding the evaluation of the information provided by stakeholders, a tendency in medium score was maintained, while that from the channels of distribution went from medium-low to medium-high for buying on-site. A uniform tendency was observed for online/other distribution channels for all three years and descriptors studied: "Internet", "Farmer on-demand", and "Cooperative consumers" (<50%). This research provides findings of implications that contribute to changing the perception of food risk, due to the COVID-19 pandemic, i.e., the adaptation of the young population, trust in safety and quality, and importance of coordination from all communication points to avoid negative or strongest consequences, in case of future lockdowns or health crisis.

MVA-CoV2-S vaccine candidate confers full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice (preprint)

The protective efficacy of vaccines against SARS-CoV-2 infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe COVID-19 disease, we report a detailed spatiotemporal description of the SARS-CoV-2 infection and replication in different areas of the brain. Remarkably, SARS-CoV-2 brain replication occurs primarily in neurons, producing important neuropathological alterations such as neuronal loss, incipient signs of neuroinflammation, and vascular damage in SARS-CoV-2 infected mice. Notably, one or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. To our knowledge, this is the first study of a COVID-19 vaccine candidate showing 100% efficacy against SARS-CoV-2 brain infection and damage, reinforcing the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19, worth to move forward into clinical trials.

Virtual screening for potential inhibitors of the molecular interaction of SARS-CoV-2 binding to the ACE2 receptor

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan, China, in December 2019, causing COVID-19 disease which are cases of SARS-like atypical pneumonia. As of December 1, 2020, México had reached 1.1 million cases of COVID-19 and 106 thousand deaths;about 63.6 million cases and 1.47 million deaths are reported worldwide with new cases and increasing mortality every day. To date there is no specific commercial treatment to control the infection. Repurpose drugs targeting the angiotensin-converting enzyme 2 (ACE2) receptor represents an alternative strategy to block the binding of SARS-COV-2 protein S and forestall virus adhesion, internalization and replication in the host cell. Rigid molecular docking was performed using RBD S1 - ACE2 (PDB: 6WV1) interaction site and 1,300 FDA approved and prescripted drugs by the Mexican Public Health System. The results were analyzed by docking score, frequency of the drug at receptor site and the types of interactions in the binding site residues. Within the top-ranked drugs identified as a potentials inhibitor of RBD S1 - ACE2 interaction we found pitavastatin, cholecalciferol, pargeverine, ipratropium, formoterol and fexofenadine, were the vast majority stands out as they are used as therapies to treat COPD, asthma and virtually any respiratory infection. Our results will serve as the basis for in vitro and in vivo studies to evaluate the potential use of these drugs to generate affordable an easily accessible therapies to treat COVID-19.

Subphenotyping of COVID-19 patients at pre-admission towards anticipated severity stratification: an analysis of 778 692 Mexican patients through an age-gender unbiased meta-clustering technique (preprint)

We apply a meta-clustering technique to discover age-gender unbiased COVID-19 patient subphenotypes based on phenotypical before admission, including pre-existing comorbidities, habits and demographic features, to study the potential early severity stratification capabilities of the discovered subgroups through characterizing their severity patterns including prognostic, ICU and morbimortality outcomes. We used the Mexican Government COVID-19 open data including 778,692 SARS-CoV-2 population-based patient-level data as of September 2020. The meta-clustering technique consists of a two-stage clustering approach combining dimensionality reduction and hierarchical clustering: 56 clusters from independent age-gender clustering analyses supported 11 clinically distinguishable meta-clusters (MCs). MCs 1-3 showed high recovery rates (90.27-95.22%), including healthy patients of all ages; children with comorbidities alongside priority in medical resources; and young obese smokers. MCs 4-5 showed moderate recovery rates (81.3-82.81%): patients with hypertension or diabetes of all ages; and obese patients with pneumonia, hypertension and diabetes. MCs 6-11 showed low recovery rates (53.96-66.94%): immunosuppressed patients with high comorbidity rate; CKD patients with poor survival length and recovery; elderly smokers with COPD; severe diabetic elderly with hypertension; and oldest obese smokers with COPD and mild cardiovascular disease. Group outcomes conformed to the recent literature on dedicated age-gender groups. These results can potentially help in the clinical patient understanding and their stratification towards automated early triage, prior to further tests and laboratory results are available, or help decide priority in vaccination or resource allocation among vulnerable subgroups or locations where additional tests are not available. Code available at: https://github.com/bdslab-upv/covid19-metaclustering

A Simple, Affordable, Rapid, Stabilized, Colorimetric, Versatile RT-LAMP assay to detect SARS-CoV-2 (preprint)

The SARS-Cov-2 pandemic has forced all countries worldwide to rapidly develop and implement widespread testing to control and manage the Coronavirus Disease 2019 (COVID-19). RT-qPCR is the gold standard molecular diagnostic method for COVID-19, mostly in automated testing platforms. These systems are accurate and effective, but also costly, time-consuming, high technological, infrastructure dependent and currently suffer from commercial reagent supply shortages. The reverse-transcription loop-mediated isothermal amplification (RT-LAMP) can be used as alternative testing method. Here, we present a novel versatile (real-time and colorimetric) RT-LAMP for the simple (one-step) and rapid (as soon as 9 min) detection of SARS-CoV-2 and demonstrate the assay on RT-qPCR-positive clinical samples. We further transformed the RT-LAMP into a dry format for room-temperature storage suitable for potentially ready-to-use COVID-19 diagnosis. After further testing and validation, the Dry-RT-LAMP could be easily applied both in developed and in low-income countries yielding rapid and reliable results.

Describing variability in pig genes involved in coronavirus infections: towards a One Health perspective in conservation of animal genetic resources (preprint)

Coronaviruses silently circulate in human and animal populations, causing mild to severe diseases. Therefore, livestock are important components of a “One Health” perspective aimed to control these viral infections. However, at present there is no example that considers pig genetic resources in this context. In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations. A total of 2229 variants were identified in the four candidate genes: 26% of them were not previously described; 29 variants affected the protein sequence and might potentially interact with the infection mechanisms. The results coming from this work are a first step towards a “One Health” perspective that should consider conservation programmes of pig genetic resources with twofold objectives: i) genetic resources could be reservoirs of host gene variability useful to design selection programmes to increase resistance to coronaviruses; ii) the described variability in genes involved in coronavirus infections across many different pig populations might be part of a risk assessment including pig genetic resources.

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice (preprint)

ABSTRACTVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.