Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States (preprint)

ImportanceUnderstanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. ObjectiveEstimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults ([≥]18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status. ExposureHIV infection OutcomeSevere COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. ResultsAmong 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts <350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status. Conclusions and RelevanceThe risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted. Key PointsO_ST_ABSQuestionC_ST_ABSIn 2021, among fully vaccinated people with COVID-19 breakthrough illness, was the risk of severe illness higher in people with HIV (PWH) compared to people without HIV (PWoH)? FindingsPWH with <350 cells/mm3 have a 59% increased risk of severe breakthrough illness compared to PWoH. MeaningVaccinations effectively reduce the risk of severe COVID-19 infection in both PWH and PWoH; however, PWH having a CD4 count <350 cells/mm3 are at higher risk of severe breakthrough infection compared to PWoH. PWH with moderate immune suppression should be considered for additional vaccine dosages and other risk-reduction measures.

Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans (preprint)

Background: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. Objective: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. Design: Retrospective cohort study. Setting: United States Department of Veterans Affairs (VA). Participants: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. Exposures: Self-reported race/ethnicity. Main outcome measures: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. Results: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). Conclusions: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54-75 Years (preprint)

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. Objective: To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. Design, Setting, and Participants: Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. Exposures: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and Measures: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. Results: Among Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. Conclusions and Relevance: Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.