COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination.

BACKGROUND: Studies have shown an increased risk of severe SARS-CoV-2-related (COVID-19) disease outcome and mortality for patients with cancer, but it is not well understood whether associations vary by cancer site, cancer treatment, and vaccination status. METHODS: Using electronic health record data from an academic medical center, we identified a retrospective cohort of 260,757 individuals tested for or diagnosed with COVID-19 from March 10, 2020, to August 1, 2022. Of these, 52,019 tested positive for COVID-19 of whom 13,752 had a cancer diagnosis. We conducted Firth-corrected logistic regression to assess the association between cancer status, site, treatment, vaccination, and four COVID-19 outcomes: hospitalization, intensive care unit admission, mortality, and a composite "severe COVID" outcome. RESULTS: Cancer diagnosis was significantly associated with higher rates of severe COVID, hospitalization, and mortality. These associations were driven by patients whose most recent initial cancer diagnosis was within the past 3 years. Chemotherapy receipt, colorectal cancer, hematologic malignancies, kidney cancer, and lung cancer were significantly associated with higher rates of worse COVID-19 outcomes. Vaccinations were significantly associated with lower rates of worse COVID-19 outcomes regardless of cancer status. CONCLUSIONS: Patients with colorectal cancer, hematologic malignancies, kidney cancer, or lung cancer or who receive chemotherapy for treatment should be cautious because of their increased risk of worse COVID-19 outcomes, even after vaccination. IMPACT: Additional COVID-19 precautions are warranted for people with certain cancer types and treatments. Significant benefit from vaccination is noted for both cancer and cancer-free patients.

Meta-analysis of nationwide SARS-CoV-2 infection fatality rates in India

There has been much discussion and debate around underreporting of deaths in India in media articles and in the scientific literature. In this brief report, we aim to meta-analyze the available/inferred estimates of infection fatality rates for SARS-CoV-2 in India based on the existent literature. These estimates account for uncaptured deaths and infections. We consider empirical excess death estimates based on all-cause mortality data as well as disease transmission-based estimates that rely on assumptions regarding infection transmission and ascertainment rates in India. Through an initial systematic review (Zimmermann et al., 2021) that followed PRISMA guidelines and comprised a search of databases PubMed, Embase, Global Index Medicus, as well as BioRxiv, MedRxiv, and SSRN for preprints (accessed through iSearch) on July 3, 2021, we further extended the search verification through May 26, 2022. The screening process yielded 15 studies qualitatively analyzed, of which 9 studies with 11 quantitative estimates were included in the meta-analysis. Using a random effects meta-analysis framework, we obtain a pooled estimate of nationwide infection fatality rate (defined as the ratio of estimated deaths over estimated infections) and a corresponding confidence interval. Death underreporting from excess deaths studies varies by a factor of 6.1–13.0 with nationwide cumulative excess deaths ranging from 2.6–6.3 million, whereas the underreporting from disease transmission-based studies varies by a factor of 3.5–7.3 with SARS-CoV-2 related nationwide estimated total deaths ranging from 1.4–3.4 million, through June 2021 with some estimates extending to 31 December 2021. Underreporting of infections was found previously (Zimmermann et al., 2021) to be 24.9 (relying on the latest 4th nationwide serosurvey from 14 June-6 July 2021 prior to launch of the vaccination program). Conservatively, by considering the lower values of these available estimates, we infer that approximately 95% of infections and 71% of deaths were not accounted for in the reported figures in India. Nationwide pooled infection fatality rate estimate for India is 0.51% (95% confidence interval [CI]: 0.45%– 0.58%). We often tend to compare countries across the world in terms of total reported cases and deaths. Although the US has the highest number of reported cumulative deaths globally, after accounting for underreporting, India appears to have the highest number of cumulative total deaths (reported + unreported). However, the large number of estimated infections in India leads to a lower infection fatality rate estimate than the US, which in part is due to the younger population in India. We emphasize that the age-structure of different countries must be taken into consideration while making such comparisons. More granular data are needed to examine heterogeneities across various demographic groups to identify at-risk and underserved populations with high COVID mortality;the hope is that such disaggregated mortality data will soon be made available for India.

Current Challenges with the Use of Test-Negative Designs for Modeling COVID-19 Vaccination and Outcomes.

The widespread testing for SARS-CoV-2 infection has facilitated the use of test-negative designs (TND) for modeling COVID-19 vaccination and outcomes. Despite the comprehensive literature on TND, the use of TND in COVID-19 studies is relatively new and calls for robust design and analysis to adapt to a rapidly changing and dynamically evolving pandemic and to account for changes in testing and reporting practices. In this commentary, we aim to draw the attention of researchers to COVID-specific challenges in using TND as we are analyzing data amassed over more than two years of the pandemic. We first review when and why TND works, and general challenges in TND studies presented in the literature. We then discuss COVID-specific challenges which have not received adequate acknowledgment but may add to the risk of invalid conclusions in TND studies of COVID-19.

Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 Infection (PASC) in a Large Academic Medical Center in the US.

BACKGROUND: A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by post-acute sequelae of SARS CoV-2 infection (PACS). Using electronic health record data, we aimed to characterize PASC-associated diagnoses and develop risk prediction models. METHODS: In our cohort of 63,675 patients with a history of COVID-19, 1724 (2.7%) had a recorded PASC diagnosis. We used a case-control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into phenotype risk scores (PheRSs) and evaluated their predictive performance. RESULTS: In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and sixty-nine phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the cohort with a history of COVID-19 with a 3.5-fold increased risk (95% CI: 2.19, 5.55) for PASC compared to the bottom 50%. CONCLUSIONS: The uncovered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with potential for risk stratification approaches.

A Case-Crossover Phenome-wide association study (PheWAS) for understanding Post-COVID-19 diagnosis patterns.

BACKGROUND: Post COVID-19 condition (PCC) is known to affect a large proportion of COVID-19 survivors. Robust study design and methods are needed to understand post-COVID-19 diagnosis patterns in all survivors, not just those clinically diagnosed with PCC. METHODS: We applied a case-crossover Phenome-Wide Association Study (PheWAS) in a retrospective cohort of COVID-19 survivors, comparing the occurrences of 1,671 diagnosis-based phenotype codes (PheCodes) pre- and post-COVID-19 infection periods in the same individual using a conditional logistic regression. We studied how this pattern varied by COVID-19 severity and vaccination status, and we compared to test negative and test negative but flu positive controls. RESULTS: In 44,198 SARS-CoV-2-positive patients, we foundenrichment in respiratory,circulatory, and mental health disorders post-COVID-19-infection. Top hits included anxiety disorder (p = 2.8e-109, OR = 1.7 [95 % CI: 1.6-1.8]), cardiac dysrhythmias (p = 4.9e-87, OR = 1.7 [95 % CI: 1.6-1.8]), and respiratory failure, insufficiency, arrest (p = 5.2e-75, OR = 2.9 [95 % CI: 2.6-3.3]). In severe patients, we found stronger associations with respiratory and circulatory disorders compared to mild/moderate patients. Fully vaccinated patients had mental health and chronic circulatory diseases rise to the top of the association list, similar to the mild/moderate cohort. Both control groups (test negative, test negative and flu positive) showed a different pattern of hits to SARS-CoV-2 positives. CONCLUSIONS: Patients experience myriad symptoms more than 28 days after SARS-CoV-2 infection, but especially respiratory, circulatory, and mental health disorders. Our case-crossover PheWAS approach controls for within-person confounders that are time-invariant. Comparison to test negatives and test negative but flu positive patients with a similar design helped identify enrichment specific to COVID-19. This design may be applied other emerging diseases with long-lasting effects other than a SARS-CoV-2 infection. Given the potential for bias from observational data, these results should be considered exploratory. As we look into the future, we must be aware of COVID-19 survivors' healthcare needs.

Are women leaders significantly better at controlling the contagion during the COVID-19 pandemic?

Recent media articles have suggested that women-led countries are doing better in terms of their responses to the COVID-19 pandemic. We examine an ensemble of public health metrics to assess the control of COVID-19 epidemic in women-versus men-led countries worldwide based on data available up to June 3. The median of the distribution of median time-varying effective reproduction number for women- and men-led countries were 0.89 and 1.14 respectively with the 95% two-sample bootstrap-based confidence interval for the difference (women - men) being [-0.34, 0.02]. In terms of scale of testing, the median percentage of population tested were 3.28% (women), 1.59% (men) [95% CI: (-1.29%, 3.60%)] with test positive rates of 2.69% (women) and 4.94% (men) respectively. It appears that though statistically not significant, countries led by women have an edge over countries led by men in terms of public health metrics for controlling the spread of the COVID-19 pandemic worldwide.

Assessing the added value of linking electronic health records to improve the prediction of self-reported COVID-19 testing and diagnosis.

Since the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, a focus of research has been to identify risk factors associated with COVID-19-related outcomes, such as testing and diagnosis, and use them to build prediction models. Existing studies have used data from digital surveys or electronic health records (EHRs), but very few have linked the two sources to build joint predictive models. In this study, we used survey data on 7,054 patients from the Michigan Genomics Initiative biorepository to evaluate how well self-reported data could be integrated with electronic records for the purpose of modeling COVID-19-related outcomes. We observed that among survey respondents, self-reported COVID-19 diagnosis captured a larger number of cases than the corresponding EHRs, suggesting that self-reported outcomes may be better than EHRs for distinguishing COVID-19 cases from controls. In the modeling context, we compared the utility of survey- and EHR-derived predictor variables in models of survey-reported COVID-19 testing and diagnosis. We found that survey-derived predictors produced uniformly stronger models than EHR-derived predictors-likely due to their specificity, temporal proximity, and breadth-and that combining predictors from both sources offered no consistent improvement compared to using survey-based predictors alone. Our results suggest that, even though general EHRs are useful in predictive models of COVID-19 outcomes, they may not be essential in those models when rich survey data are already available. The two data sources together may offer better prediction for COVID severity, but we did not have enough severe cases in the survey respondents to assess that hypothesis in in our study.

Estimating COVID-19 Vaccination and Booster Effectiveness Using Electronic Health Records From an Academic Medical Center in Michigan.

Introduction: Observational studies of COVID-19 vaccines' effectiveness can provide crucial information regarding the strength and durability of protection against SARS-CoV-2 infection and whether the protective response varies across different patient subpopulations and in the context of different SARS-CoV-2 variants. Methods: We used a test-negative study design to assess vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19 resulting in hospitalization, intensive care unit admission, or death using electronic health records data of 170,741 adults who had been tested for COVID-19 at the University of Michigan Medical Center between January 1 and December 31, 2021. We estimated vaccine effectiveness by comparing the odds of vaccination between cases and controls during each 2021 calendar quarter and stratified all outcomes by vaccine type, patient demographic and clinical characteristics, and booster status. Results: Unvaccinated individuals had more than double the rate of infections (12.1% vs 4.7%) and >3 times the rate of severe COVID-19 outcomes (1.4% vs 0.4%) than vaccinated individuals. COVID-19 vaccines were 62.1% (95% CI=60.3, 63.8) effective against a new infection, with protection waning in the last 2 quarters of 2021. The vaccine effectiveness against severe disease overall was 73.7% (95% CI=69.6, 77.3) and remained high throughout 2021. Data from the last quarter of 2021 indicated that adding a booster dose augmented effectiveness against infection up to 87.3% (95% CI=85.0, 89.2) and against severe outcomes up to 94.0% (95% CI=89.5, 96.6). Pfizer-BioNTech and Moderna vaccines showed comparable performance when controlling for vaccination timing. Vaccine effectiveness was greater in more socioeconomically affluent areas and among healthcare workers; otherwise, we did not detect any significant modification of vaccine effectiveness by covariates, including gender, race, and SES. Conclusions: COVID-19 vaccines were highly protective against infection and severe COVID-19 resulting in hospitalization, intensive care unit admission, or death. Administration of a booster dose significantly increased vaccine effectiveness against both outcomes. Ongoing surveillance is required to assess the durability of these findings.

Lessons from SARS-CoV-2 in India: A data-driven framework for pandemic resilience.

India experienced a massive surge in SARS-CoV-2 infections and deaths during April to June 2021 despite having controlled the epidemic relatively well during 2020. Using counterfactual predictions from epidemiological disease transmission models, we produce evidence in support of how strengthening public health interventions early would have helped control transmission in the country and significantly reduced mortality during the second wave, even without harsh lockdowns. We argue that enhanced surveillance at district, state, and national levels and constant assessment of risk associated with increased transmission are critical for future pandemic responsiveness. Building on our retrospective analysis, we provide a tiered data-driven framework for timely escalation of future interventions as a tool for policy-makers.

Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review.

BACKGROUND: This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis. METHODS: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection. RESULTS: Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39-.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44-.63) and 0.34 (95% CI, .25-.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37-.65), Europe (0.44; 95% CI, .32-.56), and United States of America (0.31; 95% CI, .21-.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26-.49), 0.25 (95% CI, .15-.38), 0.32 (95% CI, .14-.57), and 0.49 (95% CI, .40-.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17-.30), followed by memory problems (0.14; 95% CI, .10-.19). CONCLUSIONS: This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system.

Being a Public Health Statistician During a Global Pandemic

In this perspective, I first share some key lessons learned from the experience of modeling the transmission dynamics of SARS-CoV-2 in India since the beginning of the COVID-19 pandemic in 2020. Second, I discuss some interesting open problems related to COVID-19 where statisticians have a lot to contribute to in the coming years. Finally, I emphasize the need for having integrated and resilient public health data systems: good data coupled with good models are at the heart of effective policymaking.

Extending the susceptible-exposed-infected-removed (SEIR) model to handle the false negative rate and symptom-based administration of COVID-19 diagnostic tests: SEIR-fansy.

False negative rates of severe acute respiratory coronavirus 2 diagnostic tests, together with selection bias due to prioritized testing can result in inaccurate modeling of COVID-19 transmission dynamics based on reported "case" counts. We propose an extension of the widely used Susceptible-Exposed-Infected-Removed (SEIR) model that accounts for misclassification error and selection bias, and derive an analytic expression for the basic reproduction number R0 as a function of false negative rates of the diagnostic tests and selection probabilities for getting tested. Analyzing data from the first two waves of the pandemic in India, we show that correcting for misclassification and selection leads to more accurate prediction in a test sample. We provide estimates of undetected infections and deaths between April 1, 2020 and August 31, 2021. At the end of the first wave in India, the estimated under-reporting factor for cases was at 11.1 (95% CI: 10.7,11.5) and for deaths at 3.58 (95% CI: 3.5,3.66) as of February 1, 2021, while they change to 19.2 (95% CI: 17.9, 19.9) and 4.55 (95% CI: 4.32, 4.68) as of July 1, 2021. Equivalently, 9.0% (95% CI: 8.7%, 9.3%) and 5.2% (95% CI: 5.0%, 5.6%) of total estimated infections were reported on these two dates, while 27.9% (95% CI: 27.3%, 28.6%) and 22% (95% CI: 21.4%, 23.1%) of estimated total deaths were reported. Extensive simulation studies demonstrate the effect of misclassification and selection on estimation of R0 and prediction of future infections. A R-package SEIRfansy is developed for broader dissemination.

SARS-CoV-2 Infection Fatality Rates in India: Systematic Review, Meta-analysis and Model-based Estimation

Introduction:Fervourous investigation and dialogue surrounding the true number of SARS-CoV-2-related deaths and implied infection fatality rates in India have been ongoing throughout the pandemic, and especially pronounced during the nation?s devastating second wave. We aim to synthesize the existing literature on the true SARS-CoV-2 excess deaths and infection fatality rates (IFR) in India through a systematic search followed by viable meta-analysis. We then provide updated epidemiological model-based estimates of the wave 1, wave 2 and combined IFRs using an extension of the Susceptible-Exposed-Infected-Removed (SEIR) model, using data from 1 April 2020 to 30 June 2021.Methods:Following PRISMA guidelines, the databases PubMed, Embase, Global Index Medicus, as well as BioRxiv, MedRxiv and SSRN for preprints (accessed through iSearch), were searched on 3 July 2021 (with results verified through 15 August 2021). Altogether, using a two-step approach, 4,765 initial citations were screened, resulting in 37 citations included in the narrative review and 19 studies with 41datapoints included in the quantitative synthesis. Using a random effects model with DerSimonian-Laird estimation, we meta-analysed IFR1, which is defined as the ratio of the total number of observed reported deaths divided by the total number of estimated infections, and IFR2 (which accounts for death underreporting in the numerator of IFR1). For the latter, we provided lower and upper bounds based on the available range of estimates of death undercounting, often arising from an excess death calculation. The primary focus is to estimate pooled nationwide estimates of IFRs with the secondary goal of estimating pooled regional and state-specific estimates for SARS-CoV-2-related IFRs in India. We also tried to stratify our empirical results across the first and second waves. In tandem, we presented updated SEIR model estimates of IFRs for waves 1, 2, and combined across the waves with observed case and death count data from 1 April 2020 to 30 June 2021.Results:For India, countrywide, the underreporting factors (URF) for cases (sourced from serosurveys) range from 14.3 to 29.1 in the four nationwide serosurveys;URFs for deaths (sourced from excess deaths reports) range from 4.4 to 11.9 with cumulative excess deaths ranging from 1.79 to 4.9 million (as of June 2021). Nationwide pooled IFR1 and IFR2 estimates for India are 0.097% (95% confidence interval [CI]: 0.067?0.140) and 0.365% (95% CI: 0.264?0.504) to 0.485% (95% CI: 0.344?0.685), respectively, again noting that IFR2 changes as excess deaths estimates vary. Among the included studies in this meta-analysis, IFR1 generally appears to decrease over time from the earliest study end date to the latest study end date (from 4 June 2020 to 6 July 2021, IFR1 changed from 0.199 to 0.055%), whereas a similar trend is not as readily evident for IFR2 due to the wide variation in excess death estimates (from 4 June 2020 to 6 July 2021, IFR2 ranged from (0.290?1.316) to (0.241?0.651)%).Nationwide SEIR model-based combined estimates for IFR1 and IFR2 are 0.101% (95% CI: 0.097?0.116) and 0.367% (95% CI: 0.358?0.383), respectively, which largely reconcile with the empirical findings and concur with the lower end of the excess death estimates. An advantage of such epidemiological models is the ability to produce daily estimates with updated data, with the disadvantage being that these estimates are subject to numerous assumptions, arduousness of validation and not directly using the available excess death data. Whether one uses empirical data or model-based estimation, it is evident that IFR2 is at least 3.6 times more than IFR1.Conclusion:When incorporating case and death underreporting, the meta-analysed cumulative infection fatality rate in India varied from 0.36 to 0.48%, with a case underreporting factor ranging from 25 to 30 and a death underreporting factor ranging from 4 to 12. This implies, by 30 June 2021, India may have seen nearly 900 million infections and 1.7?4.9 million deaths when the reported numbers tood at 30.4 million cases and 412 thousand deaths (Coronavirus in India) with an observed case fatality rate (CFR) of 1.35%. We reiterate the need for timely and disaggregated infection and fatality data to examine the burden of the virus by age and other demographics. Large degrees of nationwide and state-specific death undercounting reinforce the call to improve death reporting within India.JEL Classifications: I15, I18

Estimating the wave 1 and wave 2 infection fatality rates from SARS-CoV-2 in India.

OBJECTIVE: There has been much discussion and debate around the underreporting of COVID-19 infections and deaths in India. In this short report we first estimate the underreporting factor for infections from publicly available data released by the Indian Council of Medical Research on reported number of cases and national seroprevalence surveys. We then use a compartmental epidemiologic model to estimate the undetected number of infections and deaths, yielding estimates of the corresponding underreporting factors. We compare the serosurvey based ad hoc estimate of the infection fatality rate (IFR) with the model-based estimate. Since the first and second waves in India are intrinsically different in nature, we carry out this exercise in two periods: the first wave (April 1, 2020-January 31, 2021) and part of the second wave (February 1, 2021-May 15, 2021). The latest national seroprevalence estimate is from January 2021, and thus only relevant to our wave 1 calculations. RESULTS: Both wave 1 and wave 2 estimates qualitatively show that there is a large degree of "covert infections" in India, with model-based estimated underreporting factor for infections as 11.11 (95% credible interval (CrI) 10.71-11.47) and for deaths as 3.56 (95% CrI 3.48-3.64) for wave 1. For wave 2, underreporting factor for infections escalate to 26.77 (95% CrI 24.26-28.81) and to 5.77 (95% CrI 5.34-6.15) for deaths. If we rely on only reported deaths, the IFR estimate is 0.13% for wave 1 and 0.03% for part of wave 2. Taking underreporting of deaths into account, the IFR estimate is 0.46% for wave 1 and 0.18% for wave 2 (till May 15). Combining waves 1 and 2, as of May 15, while India reported a total of nearly 25 million cases and 270 thousand deaths, the estimated number of infections and deaths stand at 491 million (36% of the population) and 1.21 million respectively, yielding an estimated (combined) infection fatality rate of 0.25%. There is considerable variation in these estimates across Indian states. Up to date seroprevalence studies and mortality data are needed to validate these model-based estimates.

Optimal diagnostic test allocation strategy during the COVID-19 pandemic and beyond.

Timely diagnostic testing for active SARS-CoV-2 viral infections is key to controlling the spread of the virus and preventing severe disease. A central public health challenge is defining test allocation strategies with limited resources. In this paper, we provide a mathematical framework for defining an optimal strategy for allocating viral diagnostic tests. The framework accounts for imperfect test results, selective testing in certain high-risk patient populations, practical constraints in terms of budget and/or total number of available tests, and the purpose of testing. Our method is not only useful for detecting infections, but can also be used for long-time surveillance to detect new outbreaks. In our proposed approach, tests can be allocated across population strata defined by symptom severity and other patient characteristics, allowing the test allocation plan to prioritize higher risk patient populations. We illustrate our framework using historical data from the initial wave of the COVID-19 outbreak in New York City. We extend our proposed method to address the challenge of allocating two different types of diagnostic tests with different costs and accuracy, for example, the RT-PCR and the rapid antigen test (RAT), under budget constraints. We show how this latter framework can be useful to reopening of college campuses where university administrators are challenged with finite resources for community surveillance. We provide a R Shiny web application allowing users to explore test allocation strategies across a variety of pandemic scenarios. This work can serve as a useful tool for guiding public health decision-making at a community level and adapting testing plans to different stages of an epidemic. The conceptual framework has broader relevance beyond the current COVID-19 pandemic.

Understanding the Patterns of Serological Testing for COVID-19 Pre- and Post-Vaccination Rollout in Michigan.

Testing for SARS-CoV-2 antibodies is commonly used to determine prior COVID-19 infections and to gauge levels of infection- or vaccine-induced immunity. Michigan Medicine, a primary regional health center, provided an ideal setting to understand serologic testing patterns over time. Between 27 April 2020 and 3 May 2021, characteristics for 10,416 individuals presenting for SARS-CoV-2 antibody tests (10,932 tests in total) were collected. Relative to the COVID-19 vaccine roll-out date, 14 December 2020, the data were split into a pre- (8026 individuals) and post-vaccine launch (2587 individuals) period and contrasted with untested individuals to identify factors associated with tested individuals and seropositivity. Exploratory analysis of vaccine-mediated seropositivity was performed in 347 fully vaccinated individuals. Predictors of tested individuals included age, sex, smoking, neighborhood variables, and pre-existing conditions. Seropositivity in the pre-vaccine launch period was 9.2% and increased to 46.7% in the post-vaccine launch period. In the pre-vaccine launch period, seropositivity was significantly associated with age (10 year; OR = 0.80 (0.73, 0.89)), ever-smoker status (0.49 (0.35, 0.67)), respiratory disease (4.38 (3.13, 6.12)), circulatory disease (2.09 (1.48, 2.96)), liver disease (2.06 (1.11, 3.84)), non-Hispanic Black race/ethnicity (2.18 (1.33, 3.58)), and population density (1.10 (1.03, 1.18)). Except for the latter two, these associations remained statistically significant in the post-vaccine launch period. The positivity rate of fully vaccinated individual was 296/347(85.3% (81.0%, 88.8%)).

Changes in COVID-19-related outcomes, potential risk factors and disparities over time

To investigate temporal trends in coronavirus disease 2019 (COVID-19)-related outcomes and to evaluate whether the impacts of potential risk factors and disparities changed over time, we conducted a retrospective cohort study with 249 075 patients tested or treated for COVID-19 at Michigan Medicine (MM), from 10 March 2020 to 3 May 2021. Among these patients, 26 289 were diagnosed with COVID-19. According to the calendar time in which they first tested positive, the COVID-19-positive cohort were stratified into three-time segments (T1: March–June, 2020;T2: July–December, 2020;T3: January–May, 2021). Potential risk factors that we examined included demographics, residential-level socioeconomic characteristics and preexisting comorbidities. The main outcomes included COVID-19-related hospitalisation and intensive care unit (ICU) admission. The hospitalisation rate for COVID-positive patients decreased from 36.2% in T1 to 14.2% in T3, and the ICU admission rate decreased from 16.9% to 2.9% from T1 to T3. These findings confirm that COVID-19-related hospitalisation and ICU admission rates were decreasing throughout the pandemic from March 2020 to May 2021. Black patients had significantly higher (compared to White patients) hospitalisation rates (19.6% vs. 11.0%) and ICU admission rates (6.3% vs. 2.8%) in the full COVID-19-positive cohort. A time-stratified analysis showed that racial disparities in hospitalisation rates persisted over time and the estimates of the odds ratios (ORs) stayed above unity in both unadjusted [full cohort: OR = 1.98, 95% confidence interval (CI) (1.79, 2.19);T1: OR = 1.70, 95% CI (1.36, 2.12);T2: OR = 1.40, 95% CI (1.17, 1.68);T3: OR = 1.55, 95% CI (1.29, 1.86)] and adjusted analysis, accounting for differences in demographics, socioeconomic status, and preexisting comorbid conditions (full cohort: OR = 1.45, 95% CI (1.25, 1.68);T1: OR = 1.26, 95% CI (0.90, 1.76);T2: OR = 1.29, 95% CI (1.01, 1.64);T3: OR = 1.29, 95% CI (1.00, 1.67)).