04 April, 2021

Pandemic effect on body composition. Single center analysis of 2.771 cases. -

Background: The COVID-19 pandemic has led to a dramatic increase in the levels of sedentary lifestyle and unhealthy dietary habits. A worsening in populational obesity levels and body composition (BC) is strongly awaited but so far not documented. Objective: To compare BC profile measured by bioelectrical impedance analysis (BIA) between pre-pandemic (P1-03/15th/2017 to 03/16th/2020) and pandemic (P2-3/17th/2020 to 3/10th/2021) period of time. Materials and Methods: BIA were grouped according to the time it was performed. Two comparisons were done: an independent sample comparison (ISC) and a paired sample comparison (PSC) considering patients with at least one BIA in P1 and P2. Age, height, gender, weight, body mass index (BMI), body fat mass (BFM), free fat mass (FFM), skeletal muscle mass (SMM), percentage of body fat (PBF), visceral fat area (VFA) were compared. Statistical significance level was defined for a p value<0.05. Results and Discussion: A total of 3.358 BIA were performed, and 2.771 and 112 were selected for IS and PS, respectively. In ISC, despite an unchanged weight, BFM, FFM, PBF and VFA increased and SSM decreased on P2(p<0.015 for all). A multivariated linear regression model using PBF as dependent variable showed P2 as an independent predictor (β=0.38 95%CI 0.19 to 0.56). In the PSC, PBF also increased from P1 to P2 (p=0.015). To our knowledge this is the first documentation of worsening BC after pandemic. Health authorities should be alert for this phenomenon and their clinical consequences in the days to come.

🖺 Full Text HTML: Pandemic effect on body composition. Single center analysis of 2.771 cases.

Situation of COVID-19 in Brazil: An analysis via growth models as implemented in the ModInterv system for monitoring the pandemic -

In this work we analyze the cumulative curves of deaths attributed to COVID-19 in the 26 Brazilian States and the Federal District up until August 21, 2020. Mathematical growth models implemented by the application {ModInterv COVID-19}, which can be accessed via internet browser or via a mobile app, were used to investigate at which stage the epidemic is in each of the Brazilian federal units. The analysis revealed that almost all states in the Northern and Northeastern regions were already in the saturation phase, meaning that the epidemic was relatively under control, whereas in all Southern states and in most states in the Midwest the epidemic was still accelerating or showed only a slight deceleration. The Southeastern region presented a great diversity of epidemic stages, with each state being found at a different stage, ranging from acceleration to saturation. It is argued that understanding this heterogeneous geographical distribution of the epidemic is relevant for public health authorities, as it may help in devising more effective strategies against the COVID-19 pandemic in a continental country like Brazil.

🖺 Full Text HTML: Situation of COVID-19 in Brazil: An analysis via growth models as implemented in the ModInterv system for monitoring the pandemic

Using PARIHS framework to design a community-based COVID-19 intervention in rural Ghana -

This study utilized the Promoting Action on Research Implementation in Health Services (PARIHS) framework to guide the design of the evidence-based practice, COVID Preparedness & Outbreak Prevention Plan (CoCoPOPP) for rural communities in Ghana. Through a participatory academic-community team discussion, interactive dissemination, review of evidence about community-based interventions during Ebola, HIV/AIDS, and Influenza outbreaks via snowball sampling, continuous discourse within the design team, feedback from other local stakeholders and national experts, the evidence-based intervention was developed consistent with the PARIHS framework. By applying the three core elements of the PARIHS framework (that is, evidence, context and facilitation), the study developed orientation, logistic needs and planning as well as social mobilization. The components also included participants recruitment and training, communication, research and M&E plan, execution and technical assistance and facilitation with three overall aims: (1) meet a pressing health need during the COVID-19 pandemic in local underserved settings, (2) ensure that the strategy is informed by high-quality evidence from similar interventions in past outbreaks and (3) evaluate and learn from research on interventions to garner data for organizational use and to share insights on pandemic management and control with the Ghanaian government, wider global health and education community. Hence, CoCoPOPP can be implemented across other rural communities in Ghana and beyond, particularly in other Sub-Saharan African countries with similar cultural settings.

🖺 Full Text HTML: Using PARIHS framework to design a community-based COVID-19 intervention in rural Ghana

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series -

Background. Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods. Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. Results. All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ~30-, ~8- and ~8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ~50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ~24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. Conclusions. BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

🖺 Full Text HTML: Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

covid19.Explorer: A web application and R package to explore United States COVID-19 data -

Appearing at the end of 2019, a novel virus (later identified as SARS-CoV-2) was characterized in the city of Wuhan in Hubei Province, China. As of the time of writing, the disease caused by this virus (known as COVID-19) has already resulted in close to 3 million deaths worldwide. SARS-CoV-2 infections and deaths, however, have been highly unevenly distributed among age groups, sexes, countries, and jurisdictions over the course of the pandemic. Herein, I present a tool (the covid19.Explorer R package and web application) that has been designed to explore and analyze publicly available United States COVID-19 infection and death data from the 2020/21 U.S. SARS-CoV-2 pandemic. The analyses and visualizations that this R package and web application facilitate can help users better comprehend the geographic progress of the pandemic, the effectiveness of non-pharmaceutical interventions (such as lockdowns and other measures, which have varied widely among U.S. states), and the relative risks posed by COVID-19 to different age groups within the U.S. population. The end result is an interactive tool that will help its users develop an improved understanding of the temporal and geographic dynamics of the SARS-CoV-2 pandemic, accessible to lay people and scientists alike.

🖺 Full Text HTML: covid19.Explorer: A web application and R package to explore United States COVID-19 data

Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity -

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.

🖺 Full Text HTML: Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity

The economic value of quarantine is higher at lower case prevalence, with quarantine justified at lower risk of infection -

Some infectious diseases, such as COVID-19, are so harmful that they justify broad scale social distancing. Targeted quarantine can reduce the amount of indiscriminate social distancing needed to control transmission. Finding the optimal balance between targeted vs. broad scale policies can be operationalized by minimizing the total amount of social isolation needed to achieve a target reproductive number. Optimality is achieved by quarantining on the basis of a risk threshold that depends strongly on current disease prevalence, suggesting that very different disease control policies should be used at different times or places. Aggressive quarantine is warranted given low disease prevalence, while populations with a higher base rate of infection should rely more on social distancing by all. The total value of a quarantine policy rises as case counts fall, is relatively insensitive to vaccination unless the vaccinated are exempt from distancing policies, and is substantially increased by the availability of modestly more information about individual risk of infectiousness.

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NSAIDs/Nitazoxanide/Azithromycin Immunomodulatory Protocol Used in Adults, Children and Pregnant COVID-19 Patients: An Egyptian Prospective Observational Study. -

To date no treatment protocol of proven efficacy was approved to manage COVID-19. We have developed a novel COVID-19 protocol basing on our early pioneering article that justified repurposing of nitazoxanide/azithromycin combination for early cases of COVID-19 which was followed by two articles to justify addition of non-steroidal anti-inflammatory drugs to nitazoxanide/azithromycin. We are presenting a prospective telemedicine case series involving consented 32 patients/legal guardians including 10 confirmed by PCR and 21 highly suspected COVID-19 Egyptian patients. The patients included 15 adult males, 11 adult females, 2 pregnant patients as well as 4 children. All patients have received a short 5-day-regimen of NSAIDs (diclofenac potassium in most of cases, ibuprofen, lornoxicam, celecoxib, ketoprofen or ketorolac)/nitazoxanide/azithromycin +/- cefoperazone either in full or in part as illustrated in the manuscript. The primary endpoint of this protocol was full relief of all serious COVID-19 clinical manifestations. The primary endpoint was fully achieved in all patients within two weeks. Most of the patients treated early with the protocol have fully recovered during its described five days; the leucocytic/lymphocytic count was significantly improved for those with prior leucopenia/lymphopenia. No significant adverse effects were reported. A novel 5-day-protocol to safely and effectively cure COVID-19 using repurposed inexpensive FDA approved drugs is illustrated and we recommend performing sufficiently powered double blind randomized clinical trials against any current standard protocol.

🖺 Full Text HTML: NSAIDs/Nitazoxanide/Azithromycin Immunomodulatory Protocol Used in Adults, Children and Pregnant COVID-19 Patients: An Egyptian Prospective Observational Study.

Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants -

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (67%) serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

🖺 Full Text HTML: Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants

A Second Wave? What Do People Mean By COVID Waves? - A Working Definition of Epidemic Waves -

Policymakers and researchers describe the COVID-19 epidemics by waves without a common vocabulary on what constitutes an epidemic wave, either in terms of a working definition or operationalization, causing inconsistencies and confusions. A working definition and operationalization can be helpful to characterize and communicate about epidemics. We propose a working definition of epidemic waves in the ongoing COVID-19 pandemic and an operationalization based on the public data of the effective reproduction number R. Our operationalization characterizes the numbers and durations of waves (upward and downward) in 178 countries and reveals patterns that can enable healthcare organizations and policymakers to make better description and assessment of the COVID crisis to make more informed resource planning, mobilization, and allocation temporally in the continued COVID-19 pandemic.

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Antigen-based rapid diagnostic testing or alternatives for diagnosis of symptomatic COVID-19: A simulation-based net benefit analysis -

Background: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDT) offer the ability to diagnose COVID-19 rapidly and at low cost; however, lower sensitivity than nucleic acid amplification tests (NAAT) has limited adoption of Ag-RDT in clinical settings. Methods: We compared Ag-RDT, NAAT, and clinical judgment alone for diagnosing COVID-19 among symptomatic patients. We considered two scenarios: a high-prevalence hospital setting with 24-hour NAAT turnaround, and a lower-prevalence outpatient setting with 3-day NAAT turnaround. We simulated transmission from cases and contacts and relationships between time, viral burden, transmission, and case detection. We used decision curve analysis to compare the net benefit of diagnostic approaches relying on Ag-RDT versus NAAT. Results: Greater net benefit was achieved with Ag-RDT than NAAT in the outpatient setting, as long as NAAT turnaround time was longer than one day. NAAT was predicted to offer greater net benefit than Ag-RDT in the hospital setting, unless NAAT turnaround times exceeded 2 days. Findings were robust to data-consistent variation in Ag-RDT performance, empiric isolation practices, duration of symptoms, and other model parameters. Both tests provided greater benefit than management based on clinical judgment alone, unless the available interventions carried minimal harm and could be provided at full intensity to all patients in whom COVID-19 diagnosis was considered. Conclusions: Ag-RDT may provide greater net benefit than NAAT for diagnosis of symptomatic COVID-19 in outpatient settings when NAAT turnaround times are longer than one day. NAAT is likely the optimal testing strategy for hospitalized patients, especially those with prolonged symptoms prior to admission.

🖺 Full Text HTML: Antigen-based rapid diagnostic testing or alternatives for diagnosis of symptomatic COVID-19: A simulation-based net benefit analysis

On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials -

Understandably, the recent trials for COVID-19 vaccines have garnered a considerable amount of attention and (as of this writing) vaccinations are about to begin. The popular summaries give infection rates in the vaccinated and placebo and estimated efficacy, which for the two trials we focus on (Moderna and Pfizer) are both near 95%. This paper explores the potential effects of possible false positives or false negatives (misclassification) in the COVID-19 diagnosis with specific application to the Moderna and Pfizer trials. The general conclusion, fortunately, is that these potential misclassifications almost always would lead to underestimation of the efficacy and that correcting for false positives or negatives will lead to even higher estimated efficacy.

🖺 Full Text HTML: On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials

Bored by bothering: A cost-value approach to pandemic boredom -

In an effort to mitigate the impact of the COVID-19 pandemic, countries around the world have employed non-pharmaceutical containment measures. The effectiveness of such mitigation efforts relies on individual compliance (e.g., avoiding to travel or to gather). Crucially, adhering to the required behavioral recommendations places substantial burdens on those who are asked to follow them. One particularly likely outcome of adherence should be the experience of boredom. Thus, people might get bored by bothering. Drawing from research and theorizing on reward-based decision making, we conducted a high-powered study (N = 1553 US participants) to investigate whether the value and effort people ascribe to adherence to containment measures directly and indirectly (i.e., mediated by adherence) affects their experience of boredom. As expected, structural equation modeling revealed that high value and low effort predicted compliance with behavioral recommendations. Moreover, higher compliance was linked to more boredom, meaning that high value and low effort increased boredom via compliance. In contrast, high value and low effort had direct effects on boredom in the opposite direction (i.e., decreasing boredom). Attesting to their robustness and generalizability, these findings held for both prospective (with respect to upcoming winter holidays) and retrospective behavior (with respect to previous thanksgiving holidays), across US states which had or had not enforced behavioral restrictions, individual differences in boredom proneness, and demographic variables. Taken together, our results show that people can indeed get bored by bothering: Complying with nonpharmacological containment measures like avoiding to travel and to gather can come at the cost of getting bored, an experience that was strongly linked to negative affect in our study. While the observed levels of compliance were relatively high and those of boredom were relatively low, the data suggest that this could change over time because levels of boredom might rise. This might render maintenance of compliance in the general public increasingly difficult. However, we illustrate how policy makers can rely on theoretical models of boredom and behavior to maintain compliance and discuss the chances and pitfalls of doing so.

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An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2 -

The on-going coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has infected hundreds of millions of people and killed more than two million people worldwide. Currently, there are no effective drugs available for treating SARS-CoV-2 infections; however, vaccines are now being administered worldwide to control this virus. In this study, we have studied SARS-CoV-2 helicase, Nsp13, which is critical for viral replication. We compared the Nsp13 sequences reported from India with the first reported sequence from Wuhan province, China to identify and characterize the mutations occurring in this protein. To correlate the functional impact of these mutations, we characterised the most prominent B cell and T cell epitopes contributed by Nsp13. Our data revealed twenty-one epitopes, which exhibited high antigenicity, stability and interactions with MHC class-I and class-II molecules. Subsequently, the physiochemical properties of these epitopes were also analysed. Furthermore, several of these Nsp13 epitopes harbour mutations, which were further characterised by secondary structure and per-residue disorderness, stability and dynamicity predictions. Altogether, we report the candidate epitopes of Nsp13 that may help the scientific community to understand the evolution of SARS-CoV-2 variants and their probable implications.

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Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors -

SARS-CoV-2 infection initiates with the attachment of spike protein to the ACE2 receptor. While vaccines have been developed, no SARS-CoV-2 specific small molecule inhibitors have been approved. Herein, utilizing the crystal structure of the ACE2/Spike receptor binding domain (S-RBD) complex in computer-aided drug design (CADD) approach, we docked ~8 million compounds within the pockets residing at S-RBD/ACE2 interface. Five best hits depending on the docking score, were selected and tested for their in vitro efficacy to block SARS-CoV-2 replication. Of these, two compounds (MU-UNMC-1 and MU-UNMC-2) blocked SARS-CoV-2 replication at sub-micromolar IC50 in human bronchial epithelial cells (UNCN1T) and Vero cells. Furthermore, MU-UNMC-2 was highly potent in blocking the virus entry by using pseudoviral particles expressing SARS-CoV-2 spike. Finally, we found that MU-UNMC-2 is highly synergistic with remdesivir (RDV), suggesting that minimal amounts are needed when used in combination with RDV, and has the potential to develop as a potential entry inhibitor for COVID-19.

🖺 Full Text HTML: Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors

Covid-19 Sentry

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