COVID-19 vaccine effectiveness among South Asians in Ontario: A test-negative design population-based case-control study (preprint)

Objectives: To: 1) evaluate the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians, and 2) compare the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. Design: Test negative design study Setting: Ontario, Canada between Dec 14, 2020 and Nov 15, 2021 Participants: All eligible individuals >18 years with symptoms of COVID-19 and subdivided by South Asian ethnicity versus other, and those who were vaccinated versus non-vaccinated. Main Outcome measures: The primary outcome was vaccine effectiveness as defined by COVID-19 infections, hospitalizations, and deaths, and secondary outcome was the odds of COVID-19 infections, hospitalizations, and death comparing non-vaccinated South Asians to non-vaccinated non-South Asians. Results: 883,155 individuals were included. Among South Asians, two doses of COVID-19 vaccine prevented 93.8% (95% CI 93.2, 94.4) of COVID-19 infections and 97.5% (95% CI 95.2, 98.6) of hospitalizations and deaths. Among non-South Asians, vaccines prevented 86.6% (CI 86.3, 86.9) of COVID-19 infections and 93.1% (CI 92.2, 93.8) of hospitalizations and deaths. Non-vaccinated South Asians had higher odds of symptomatic SARS-CoV-2 infection compared to non-vaccinated non-South Asians (OR 2.35, 95% CI 2.3, 2.4), regardless of their immigration status. Conclusions: COVID-19 vaccines are effective in preventing infections, hospitalizations and deaths among South Asians living in Canada. The observation that non-vaccinated South Asians have higher odds of symptomatic COVID-19 infection warrants further investigation.

What factors converged to create a COVID-19 hot-spot? Lessons from the South Asian community in Ontario. (preprint)

Background: South Asians represent the largest non-white ethnic group in Canada. The Greater Toronto Area (GTA), home to a high proportion of South Asians, emerged as a COVID-19 hot spot. Early in the pandemic, the South Asian community was identified as having risk factors for exposure and specific barriers to accessing testing and reliable health information, rendering them uniquely vulnerable to SARS-CoV-2 infection. Objectives: To investigate the burden of SARS-CoV-2 infection among South Asians in the GTA, and to determine which demographic characteristics were most closely aligned with seropositivity, in this cross-sectional analysis of a prospective cohort study. Methods: Participants from the GTA were enrolled between April and July 2021. Seropositivity for anti-spike and anti-nucleocapsid antibodies was determined from dried blood spots, and age and sex standardized to the Ontario South Asian population. Demographics, risk perceptions, and sources of COVID-19 information were collected via questionnaire in a subset. Results: Among the 916 South Asians enrolled, mean age 41 years, the age and sex standardized seropositivity was 23.6% (95% CI: 20.8%-26.4%). Approximately one-third identified as essential workers, and 19% reported living in a multi-generational household. Over half perceived high COVID-19 risk due to their geographic location, and 36% due to their type of employment. The top three most trusted sources of COVID-related information included healthcare providers/public health, traditional media sources, and social media. Conclusion: By the third wave of the COVID-19 pandemic, approximately one-quarter of a sample of South Asians in Ontario had serologic evidence of prior SARS-CoV-2 infection. Insight into factors that render certain populations at risk can help future pandemic planning and disease control efforts.

Older Age and Frailty Are Associated With Higher Mortality but Lower Intensive Care Unit Admission Among Adults Admitted to Canadian Hospitals With COVID-19: A Report From the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance Network (preprint)

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Adult patients with laboratory-confirmed COVID-19 admitted to eleven sites in Ontario, Quebec, Alberta and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Age, sex, demographics, housing, exposure characteristics, Clinical Frailty Scale, comorbidities, and outcomes including length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were conducted. Descriptive analyses and multivariable logistic regressions were conducted. Findings: Among 2011 patients, mean age was 71·0 (range 19-105) years. 45·7% were women and 74·0% were white. 21·5% were admitted from Assisted Living facilities, 8·2% from long term care, and 2·1% from homeless shelters. The full spectrum of frailty was represented in both younger and older age groups. The majority (61·7% of adults <65 and 91·2% of those >=65) had at least one underlying comorbidity and 27·2% had obesity. Mortality was 14·3% among those not admitted to ICU, and 24·6% for those admitted to ICU. Older age and higher frailty were associated with reduced ICU admission but increased mortality. Obesity was independently associated with ICU admission but not with death. Associations between underlying comorbidities and adverse outcomes were attenuated but persisted when adjusting for frailty.Interpretation: Frailty and age were independent predictors of lower ICU use and higher mortality; when accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened.Funding Statement: Funding was provided by the Public Health Agency of Canada and the Canadian Institutes of Health Research.Declaration of Interests: MKA reports grant funding from the Public Health Association of Canada, CIHR, Canadian Frailty Network, Sanofi Pasteur and GSK group of companies, and payments from Pfizer, Sanofi Pasteur and Seqirus outside the submitted work. AM reports payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. JEM reports payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work. TFH reports grants from Pfizer and GSK. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. JG, JJL, GB, LV, ME, DM-C, AA, KW, ST, SS, AMc and KK report no conflicts of interest.Ethics Approval Statement: The protocol for active COVID-19 surveillance has been approved by each local site’s Research Ethics Board.

Prophylaxis for covid-19: living systematic review and network meta-analysis (preprint)

Objective To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021. Study selection Randomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomized trials: six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision, and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain. Conclusion Hydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Funding This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321). Reader note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials (preprint)

Objectives: To assess the overall effect of vitamin D supplementation on risk of acute respiratory infection (ARI), and to identify factors modifying this effect. Design: We conducted a systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard RCT Number (ISRCTN) registry from inception to May 2020. Eligibility Criteria for Selecting Studies: Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Results: We identified 40 eligible RCTs (total 30,956 participants, aged 0 to 95 years). Data were obtained for 29,841 (96.5%) of 30,909 participants in 39 studies. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.89, 95% CI 0.81 to 0.98; P for heterogeneity 0.009). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of [≤]12 months (OR 0.82, 95% CI 0.72 to 0.94). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.94, 95% CI 0.81 to 1.08). Risk of bias within individual studies was assessed as being low for all but two trials. A funnel plot showed asymmetry, suggesting that small trials showing non-protective effects of vitamin D may have been omitted from the meta-analysis. Conclusions: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. The overall effect size may have been over-estimated due to publication bias. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.

Physical Distancing, Face Masks, and Eye Protection to Prevent Person-Person COVID-19 Transmission: A Systematic Review and Meta-Analysis (preprint)

Background: Coronavirus disease 2019 (COVID-19) is spread person to person by virus through close contact. The optimal person-person distance and use of facemasks and/or eye protection to prevent disease transmission in healthcare and non-healthcare settings is debated.Methods: We systematically reviewed the impact of distance, masks, and eye protection on transmission of COVID-19, SARS, or MERS from 21 standard, World Health Organization (WHO)-specific and COVID-19-specific data sources from inception to April 15, 2020 for studies of any design and language 1) comparing different distances between those infected and the people close to them, mask use, or eye protection, or 2) contextual factors of acceptability, feasibility, resource use, and equity of these interventions. We screened studies, extracted data, and assessed risk of bias in duplicate. Frequentist and Bayesian meta-analyses and meta-regression for the main outcome of viral transmission were by random effects. Secondary outcomes were contextual factors. We rated certainty of evidence rating per GRADE. PROSPERO: 177047.Findings: We identified 0 RCTs and 164 relevant observational studies in healthcare and non-healthcare (community) settings from 16 countries across 6 continents. A physical distance of one metre or more compared to less than one metre from those infected was associated with 1) a lower risk of viral transmission (n=7782, 5.3% vs 15.5%; RD -10.2% [95%CI -11.5% to -7.5%], pooled adjusted odds ratio [aOR] 0.18 [95%CI 0.09-0.38], moderate certainty) and 2) incremental benefits with increasing distance, change in relative risk (RR) per metre 1.57 (moderate certainty). Facemask use was associated with less infection (n=2647, 2.7% vs 17.4%; RD -14.% [95% credible interval [CrI] -15.9% to -10.7%]; aOR 0.15 [95%CrI 0.07-0.34], low certainty), with stronger associations with N95 or similar (including powered) respirators compared to disposable surgical or similar (e.g. reusable 12-16-layer cotton) masks, p interaction =0.090; posterior probabilities for RR<1 of N95 vs surgical masks were >95% despite minimally informative priors; moderate certainty). Eye protection was associated with quantitatively similar lower risk of infection in 2 adjusted and 15 unadjusted studies (n=3751, 5.4% vs 16.0%; RD -10.6 [95%CI -12.5% to -7.7%]; RR 0.34 [95%CI 0.22-0.52]; aOR 0.22 [95%CI 0.12-0.39], low certainty).Interpretation: This meta-analysis supports physical distancing by more than one metre and provides quantitative estimates for models and contact tracing to inform policy. Although direct evidence is limited, the optimal use of masks, in particular N95 or similar respirators, may depend on risk assessment and contextual factors. Eye protection may provide significant additional benefits. Globally collaborative, well-conducted studies on preventative and therapeutic strategies are required but are challenging to achieve immediately and, thus, recommendations in the interim to curtail the COVID-19 pandemic should be informed by this systematic appraisal of current evidence.Funding Statement: Commissioned by the World Health Organization as a rapid review on March 25, 2020. The funders of the study helped with defining the scope of the question, but otherwise had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit it.Declaration of Interests: ML is an investigator of an ongoing clinical trial on medical masks versus N95 respirators for COVID-19 (NCT04296643). All other authors declare no competing interests. Ethics Approval Statement: The authors prospectively submitted the systematic review protocol for registration on PROSPERO (submission number 177047). This study followed PRISMA and MOOSE reporting guidelines.