Reverse Engineering the Reproduction Number: A Framework for Data-Driven Counterfactual Analysis, Strategy Evaluation, and Feedback Control of Epidemics (preprint)

During the COVID-19 pandemic, different countries, regions, and communities constructed various epidemic models to evaluate spreading behaviors and assist in making mitigation policies. Model uncertainties, introduced by complex transmission behaviors, contact-tracing networks, time-varying spreading parameters, and human factors, as well as insufficient data, have posed arduous challenges for model-based approaches. To address these challenges, we propose a novel framework for data-driven counterfactual analysis, strategy evaluation, and feedback control of epidemics, which leverages statistical information from epidemic testing data instead of constructing a specific model. Through reverse engineering the reproduction number by quantifying the impact of the intervention strategy, this framework tackles three primary problems: 1) How severe would an outbreak have been without the implemented intervention strategies? 2) What impact would varying the intervention strength have had on an outbreak? 3) How can we adjust the intervention intensity based on the current state of an outbreak? Specifically, we consider the epidemic intervention policies such as the testing-for-isolation strategy as an example, which was successfully implemented by the University of Illinois Urbana-Champaign (UIUC) and Purdue University (Purdue) during the COVID-19 pandemic. By leveraging data collected by UIUC and Purdue, we validate the effectiveness of the proposed data-driven framework.

Shifts in COVID-19 Vaccine acceptance rates among African countries: A systematic review and Meta-analysis (preprint)

Objective: To provide a comparative systematic review and meta-analysis of COVID-19 vaccine acceptance rates in African countries and their predictors. Methods: : Fifteen studies on COVID-19 vaccine acceptance rate s in African countries were reviewed in the Medline database via PubMed. Meta-analysis investigated the summary effect and inter-study heterogeneity of vaccine acceptance rates and influential factors. Results: : Overall, the COVID-19 vaccine acceptance rate was 71% (95% CI 64-77). As time passed, the vaccine acceptance rate decreased (second half of 2020: 81%, first half of 2021: 67%). Also, the vaccine acceptance rates in urban areas were higher than in rural areas (urban: 82%, rural: 72%). When considering region, vaccine acceptance rates in Eastern and Southern African countries were higher than in Western and North African countries (East: 72%, South: 72%, West: 60%, North: 52%). Finally, factors such as older age, male sex, and wealth were identified as factors associated with a more acceptive attitude toward vaccination. Conclusions: : COVID-19 vaccine acceptance rates demonstrated shifts and was affected by several factors. The rates decreased over time, were lower in rural (vs. urban) settings, and were relatively low in Northern and West African countries (vs. Southern and East African countries). We also found differences in vaccine acceptance rates by some socio-demographic characteristics. Targeting these characteristics, devising strategies to improve vaccine uptake in Africa could help improve vaccination rates.

Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection (preprint)

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we deep sequenced saliva and nasal samples collected daily from immune and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both naive and immune individuals appeared largely stochastic; however, we identified clear mutational hotspots within the viral genome, consistent with selection and differing between naive and immune individuals. In rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of virus between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.

BIOLOGICS AND COVID-19 OUTCOMES IN INFLAMMATORY BOWEL DISEASE PATIENTS

Introduction Both clinicians and inflammatory bowel disease (IBD) patients remain concernedthat either their disease or medications—namely biologics, may increase the risk ofsevere adverse outcomes from coronavirus disease-2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to assess the safety of biologicsin COVID-19 patients with IBD.Methods We performed a systematic review of the databases PubMed/Medline, Embase,Cochrane, Web of Science, LitCOVID-NIH, and WHO COVID-19 from January 1-November3, 2020, to identify relevant articles reporting outcomes in IBD patients with COVID-19.Studies were excluded if they did not report the outcomes of interest (intensive care unit(ICU) admission, mechanical ventilation, and mortality) or excluded data on IBD medications(biologics). Pooled analysis was performed using a random-effects model and multivariateregression was applied.Results The initial search yielded a total of 81 articles, of which a total of 12 studies with2,681 patients were finally included. We found the overall prevalence of outcomes for allIBD patients as: need for mechanical ventilation: 5.1% (95% CI: 3.5%–7.4%, I2 = 52.1%),need for ICU admission: 6.1%, (95% CI: 4.2%-8.8%, I2 = 54.8%), and overall mortality:4.5% (95% CI: 2.8%-7.1%, I2 = 68.0) (Figure 1). Use of biologics did not show a moderatingeffect on the need for mechanical ventilation (coefficient: -0.01, 95% CI -0.08 – 0.05, p =0.68), ICU admission (coefficient: 0.03, 95% CI: -0.02 – 0.08, p = 0.27), or mortality(coefficient: 0.03, 95% CI -0.01 – 0.07, p = 0.20) (Figure 2).Discussion We found the overall prevalence of “severe” COVID-19—mechanical ventilation,ICU admission, and mortality, for all IBD patients with COVID-19 to be 5.1%, 6.1%, and4.5%, respectively. This appears to be fairly low given the impact IBD and its medicationsmay have on the immune-system. We also found that the use of biologics did not predict“severe” COVID-19—as shown upon multivariable analysis from our meta-regression model.This finding is important as it advocates for the ongoing and continued IBD therapy (biologics)in patients during the COVID-19 pandemic. The incidence, severity, and outcomes relatedto COVID-19 in IBD patients needs to be reassessed as data continues to emerge from thepandemic. Additional outcomes data will be required to understand how all classes ofbiologics and/or the use of concomitant immunosuppressants effect COVID-19 outcomesin IBD patients.(Figure Presented)Figure 1. Forrest plot demonstrating the overall prevalence of outcomes—(A) need for mechanical ventilation, (B) need for ICU admission, and (C) overall mortality—in COVID-19 infected inflammatory bowel disease (IBD) patients.(Figure Presented)Figure 2. Scatter plots demonstrating the impact of biologics on outcomes;(A) need for mechanical ventilation, (B) need for ICU admission, and (C) overall mortality.

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution (preprint)

The global effort to vaccinate people against SARS-CoV-2 in the midst of an ongoing pandemic has raised questions about the nature of vaccine breakthrough infections and the potential for vaccinated individuals to transmit the virus. These questions have become even more urgent as new variants of concern with enhanced transmissibility, such as Delta, continue to emerge. To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis.

The efficacy of tocilizumab (TOC), monoclonal antibody against interleukin-6 (IL-6) receptor, in patients with coronavirus disease-2019 (COVID-19) patients has led to conflicting results. We performed a systematic review and meta-analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID-19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian-Laird/Random-effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: -0.06; CI: -0.12 to -0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: -0.12; CI: -0.18 to -0.06; p < .01) and need for mechanical ventilation (RD: -0.11; CI: -0.19 to -0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID-19. Randomized controlled trials are needed to validate this.

The Association of "Loss of Smell" to COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: The presence of olfactory dysfunction or "loss of smell" has been reported as an atypical symptom in patients with coronavirus disease 2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to evaluate the prevalence of "loss of smell" in COVID-19 as well as its utility for prognosticating the disease severity. METHODS: An exhaustive search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, LitCovid NIH, and WHO COVID-19 database was conducted through August 6th, 2020. All studies reporting the prevalence of "loss of smell" (anosmia and/or hyposmia/microsmia) in laboratory-confirmed COVID-19 patients were included. Pooled prevalence for cases (positive COVID-19 through reverse transcriptase (RT-PCR) and/or serology IgG/IgM) and controls (negative RT-PCR and/or serology) was compared, and the odds ratio (OR), 95% confidence interval (CI) and the p-value were calculated. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 51 studies with 11074 confirmed COVID-19 patients were included. Of these, 21 studies used a control group with 3425 patients. The symptom of "loss of smell" (OR: 14.7, CI: 8.9-24.3) was significantly higher in the COVID-19 group when compared to the control group. Seven studies comparing severe COVID-19 patients with- and without "loss of smell" demonstrated favorable prognosis for patients with "loss of smell" (OR: 0.36, CI 0.27-0.48). CONCLUSIONS: Olfactory dysfunction or "loss of smell" is a prevalent symptom in COVID-19 patients. Moreover, COVID-19 patients with "loss of smell" appear to have a milder course of the disease.

Comparative Efficacy of N95, Surgical, Medical, and Non-Medical Facemasks in Protection of Respiratory Virus Infection: A Living Systematic Review and Network Meta-Analysis (preprint)

Background: Current facemask guidelines for respiratory viruses vary, impeding policymakers and the general population in determining which facemasks are effective as personal protective equipment (PPE). We aimed to evaluate the comparative efficacy of N95, surgical/medical, and non-medical facemasks in preventing respiratory virus infection.Methods: This living systematic review and network meta-analysis (NMA) incorporated 31 published and unpublished randomised controlled trials (RCTs) and observational studies investigating specific mask efficacy against influenza virus, SARS-CoV-1, MERS-CoV, and SARS-CoV-2. We searched PubMed, Google Scholar, and medRxiv databases for studies published up to 22 October 2020 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection.Findings: N95 or equivalent masks were the most effective in conferring protection against coronavirus infections (RR, 0.37; 95% CI, 0.24–0.55; p < 0.001) consistently across subgroup analyses of causative viruses (SARS-CoV-1/MERS-CoV versus SARS-CoV-2) and clinical settings (community setting versus healthcare setting). There was a consistent trend towards reduced coronavirus and influenza infection rates with surgical or medical facemasks, albeit without reaching statistical significance; surgical or medical masks may show effect but lack in statistical power at this stage to detect a difference.Interpretation: Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the efficacies may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., FFP2 and KN95) in both community and healthcare settings.Funding: There was no funding source for this study.Declaration of Interests: We declare no competing interests.

Gastrointestinal predictors of severe COVID-19: systematic review and meta-analysis.

BACKGROUND: COVID-19 pandemic has created a need to identify potential predictors of severe disease. We performed a systematic review and meta-analysis of gastrointestinal predictors of severe COVID-19. METHODS: An extensive literature search was performed using PubMed, Embase, Web of Science and Cochrane. Odds ratio (OR) and mean difference (MD) were calculated for proportional and continuous outcomes using a random-effect model. For each outcome, a 95% confidence interval (CI) and P-value were generated. RESULTS: A total of 83 studies (26912 patients, mean age 43.5±16.4 years, 48.2% female) were included. Gastrointestinal predictors of severe COVID-19 included the presence of diarrhea (OR 1.50, 95%CI 1.10-2.03; P=0.01), elevated serum aspartate aminotransferase (AST) (OR 4.00, 95%CI 3.02-5.28; P<0.001), and elevated serum alanine aminotransferase (ALT) (OR 2.54, 95%CI 1.91-3.37; P<0.001). Significantly higher levels of mean AST (MD 14.78 U/L, 95%CI 11.70-17.86 U/L; P<0.001), ALT (MD 11.87 U/L, 95%CI 9.23-14.52 U/L; P<0.001), and total bilirubin (MD 2.08 mmol/L, 95%CI 1.36-2.80 mmol/L; P<0.001) were observed in the severe COVID-19 group compared to non-severe COVID-19 group. CONCLUSION: Gastrointestinal symptoms and biomarkers should be assessed early to recognize severe COVID-19.

Correlates of Financial Concerns and Symptoms of Depression and Posttraumatic Stress Disorder in Impoverished Urban-dwelling Individuals in Bangladesh During the COVID-19 Pandemic: Face-to-face Interview Findings (preprint)

Background: The COVID-19 pandemic has impacted the physical, mental and financial health of many individuals. How substantially marginalized groups like impoverished urban-dwelling individuals are specifically impacted amid this pandemic is poorly understood. The present study aimed to investigate correlates of financial concerns and symptoms of depression and posttraumatic stress disorder (PTSD) during the COVID-19 pandemic among impoverished urban-dwelling individuals residing in Dhaka, Bangladesh. Methods: A cross-sectional survey was conducted between August and September 2020 using face-to-face interviews in six disadvantaged neighborhoods (“slums”) in Dhaka. Individuals were interviewed using a structured questionnaire consisting of questions assessing socio-demographics, lifestyle, financial well-being relating to the COVID-19 pandemic, depression, and PTSD. Results: A total of 435 individuals (male=54.7%; mean age=45.0±12.0 years; age range=18-85 years) participated. Most (96.3%) reported that their household income decreased due to the COVID-19 pandemic. Associated factors included female gender, primary education, jobless, food scarcity, and depression. Depression symptoms were linked to female gender, being jobless, being divorced, living in a joint family, excessive sleep, and smoking. Low incomes, excessive sleep, joblessness, and food scarcity were positively associated with PTSD symptoms. In contrast, less sleep appeared protective against PTSD. Limitations: Potential limitations included cross-sectional study design and limited sample size. Conclusions: Public health initiatives, in particular mental health services, should be introduced to mitigate against psychological and financial effects of the pandemic on impoverished urban-dwelling individuals in Bangladesh.

A Data-Informed Approach for Analysis, Validation, and Identification of COVID-19 Models (preprint)

The COVID-19 pandemic has generated an enormous amount of data, providing a unique opportunity for modeling and analysis. In this paper, we present a data-informed approach for building stochastic compartmental models that is grounded in the Markovian processes underlying these models. Our initial data analyses reveal that the SIRD model -- susceptiple (S), infected (I), recovered (R), and death (D) -- is not consistent with the data. In particular, the transition times expressed in the dataset do not obey exponential distributions, implying that there exist unmodeled (hidden) states. We make use of the available epidemiological data to inform the location of these hidden states, allowing us to develop an augmented compartmental model which includes states for hospitalization (H) and end of infectious viral shedding (V). Using the proposed model, we characterize delay distributions analytically and match model parameters to empirical quantities in the data to obtain a good model fit. Insights from an epidemiological perspective are presented, as well as their implications for mitigation and control strategies.

Knowledge, attitudes and practices associated with the COVID-19 among slum dwellers resided in Dhaka City: A Bangladeshi interview-based survey (preprint)

Background: The emergent COVID-19 has impacted unprecedentedly to all classes of people. Slum-dwellers' knowledge, attitudes and practices (KAP) towards COVID-19 are currently poorly understood. To investigate the KAP towards COVID-19 among slum dwellers resided in Dhaka City, Bangladesh. Methods: A cross-sectional offline survey was carried out enrolling 406 slum dwellers (53.2% male; mean age=44.9 years [SD=12.1]; age range=18-85 years) between August and September, 2020. The face to face interview was conducted to collect data from 6 selected slum areas in Dhaka City using convenience sampling. The questionnaire consisted of informed consent along with questions concerning observational checklists, socio-demographics, and KAP. Results: A sizeable minority were observed without wearing face masks during the survey periods (18.2%) and a vast portion (97.5%) without any hand protection. The mean scores of KAP were 6.1plus-or-minus sign2.6 (out of 17), 12.3plus-or-minus sign1.7 (out of 14), and 9.8plus-or-minus sign1.6 (out of 12), respectively. Moreover, the KAP were strongly and positively correlated with each other. Conclusions: The findings revealed that the majority of slum dwellers in Bangladesh have limited knowledge of COVID-19. Poor practices (i.e., face mask and hand protection) were directly observed during the survey. The findings suggest the immediate implementation of health education programs and adequate interventions.

Moderate to vigorous physical activity and sedentary behavior change in self-isolating adults during the COVID-19 pandemic in Brazil: A cross-sectional survey exploring correlates (preprint)

BackgroundSelf-distancing measures imposed major changes in daily life. This study aimed to (i) evaluate the changes (pre-versus during pandemic) in time spent in moderate to vigorous physical activity (MVPA) and sedentary behavior (SB) in self-isolating Brazilians during the COVID-19 pandemic, and (ii) to explore correlates of MVPA and SB. MethodsA cross-sectional self-report online survey, evaluating the time spent in MVPA and SB pre and during the COVID-19 pandemic. Sociodemographic, behavioral, clinical, variables, and time in self-isolation were also obtained. Changes in MVPA and SB and their correlates were explored using generalized estimating equations (GEE). ResultsA total of 877 participants (72.7% women, 53.7% young adults [18-34 years]) were included. Overall, participants reported a 59.7% reduction (95%CI:35.6 to 82.2) in time spent on MVPA during the pandemic. Time spent in SB increased 42.0% (95%CI:31.7 to 52.5). Greater reductions in MVPA and/or increases in SB were seen in younger adults, those not married, those employed and those with a self-reported previous diagnosis of a mental disorder. ConclusionsPeople in self-isolation significantly reduced MVPA levels and increased SB. Public health strategies should be implemented during epidemic times to mitigate the impact of self-isolation on MVPA and SB, particularly in vulnerable groups.

Type and frequency of ocular and other known symptoms experienced by people who self diagnosed as suffering from COVID-19 in the UK (preprint)

Background: Recent literature suggests that ocular manifestations present in people suffering from COVID-19. However, the prevalence and the type of ocular symptoms varies substantially, and most studies report retrospective data from patients suffering from more serious versions of the disease. Little is known of exactly which ocular symptoms manifest in people with milder forms of COVID-19. Methods: An online questionnaire obtained self-report data from people in the community, who reported to be inflicted with COVID-19. The type and frequency of different symptoms suffered during COVID-19 were obtained. Details of any pre-existing ocular conditions and the duration of symptoms of COVID-19 were ascertained. Results: Data from 132 participants showed that the four most reported COVID-19 symptoms were Dry Cough (63%), Fever (67%), Fatigue (83%), and loss of Smell/Taste (63%). 56% of the participants reported to having experienced an eye symptom, 46% reported to having a new or different eye symptom compared to pre-COVID-19 state. Three ocular symptoms (watery eyes, sore eyes, sensitivity to light) were significantly different from Pre-COVID-19 state (p<0.05). Logistic regression showed a significant association of eye symptoms with Fever (p=0.035). Conclusion: Nearly half of the sample of people studied experienced ocular symptoms. The significant ocular symptoms, indicative of viral conjunctivitis, might have been missed in patients with more serious manifestations of the disease. It is also important to differentiate between the types of ocular manifestation, as symptoms of bacterial conjunctivitis (i.e. mucous discharge, gritty eyes) were not significant. Possible mechanisms for SARS-CoV-2 infection within the eye are discussed.

Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case. (preprint)

Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, the estimation of the pandemics case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. A proportion meta-analysis was carried out on CFR in every country reporting COVID-19 cases. Based on the results, we performed a meta-analysis for global COVID-19 CFR. Each analysis was performed on two different calculations of CFR: according to calendar date and according to days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR concurrently based on the date of the first confirmed case as well as on a daily basis. For the first time, we showed that using meta-analyses, according to calendar date and days since the outbreak of the first confirmed case were different. We propose that CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics.