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 infections post-vaccination by HIV status in the United States (preprint)

ImportanceRecommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. ObjectiveEstimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals [≥]18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. ExposureHIV infection OutcomeCOVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. ResultsAmong 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. Conclusions and RelevanceCOVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.

Characterization of clinical progression of COVID-19 patients in Shenzhen, China (preprint)

Background: Understanding clinical progression of COVID-19 is a key public health priority that informs resource allocation during an emergency. We characterized clinical progression of COVID-19 and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources. Methods and Findings: The study is a single-center, observational study with prospectively collected data from all 420 patients diagnosed with COVID-19 and hospitalized in Shenzhen between January 11th and March 10th, 2020 regardless of clinical severity. Using competing risk regressions according to the methods of Fine and Gray, we found that males had faster clinical progression than females in the older age group and the difference could not be explained by difference in baseline conditions or smoking history. We estimated the proportion of cases in each severity stage over 80 days following symptom onset using a nonparametric method built upon estimated cumulative incidence of key clinical events. Based on random survival forest models, we stratified cases into risk sets with very different clinical trajectories. Those who progressed to the severe stage (22%,93/420), developed acute respiratory distress syndrome (9%,39/420), and were admitted to the intensive care unit (5%,19/420) progressed on average 9.5 days (95%CI 8.7,10.3), 11.0 days (95%CI 9.7,12.3), and 10.5 days (95%CI 8.2,13.3), respectively, after symptom onset. We estimated that patients who were admitted to ICUs remained there for an average of 34.4 days (95%CI 24.1,43.2). The median length of hospital stay was 21.3 days (95%CI, 20.5,22.2) for cases who did not progress to the severe stage, but increased to 52.1 days (95%CI, 43.3,59.5) for those who required critical care. Conclusions: Our analyses provide insights into clinical progression of cases starting early in the course of infection. Patient characteristics near symptom onset both with and without lab parameters have tremendous potential for predicting clinical progression and informing strategic response.