People with HIV Have Higher Risk of COVID-19 Diagnosis but Similar Outcomes than the General Population

BackgroundWe investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and to comorbidity burden. MethodsRetrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV IPWs), and combined models. Among PWH, we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did or did not develop study outcomes using receiver operating characteristic analysis. ResultsBetween March and November 2020, 63,319 people were receiving primary care services at UCSD, of whom 4,017 were people living with HIV (PWH). PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared to those without HIV after weighting for potential testing bias, comorbidity burden, and HIV-IPW (95% CI 1.6-2.8). Relative to persons without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR): 0.5, 95% CI: 0.1 - 1.4]. PWH had neither a different rate of ICU admission (aIRR:1.08, 95% CI; 0.31 - 3.80) nor in-hospital death (aIRR:0.92, 95% CI; 0.08 - 10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. ConclusionsPWH have a higher risk of COVID-19 diagnosis but similar outcomes compared to those without HIV. Summary pointAfter considering the effects of potential bias due to differential testing, comorbidities, and other patient characteristics, people with HIV had an increased rate of SARS-CoV-2 positivity and similar rates of hospitalization, ICU admission, and death.

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma

BACKGROUNDThe efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODSThis multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults [≥]18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTSA total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSIONEarly administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. Trial RegistrationClinicalTrials.gov number, NCT04373460.

Factors associated with severity of COVID-19 disease in a multicenter cohort of people with HIV in the United States, March-December 2020

BackgroundUnderstanding the spectrum of SARS-CoV-2 infection and COVID-19 disease in people with HIV (PWH) is critical to provide clinical guidance and implement risk-reduction strategies. ObjectiveTo characterize COVID-19 in PWH in the United States and identify predictors of disease severity. DesignObservational cohort study. SettingGeographically diverse clinical sites in the CFAR Network of Integrated Clinical Systems (CNICS) ParticipantsAdults receiving HIV care through December 31, 2020. MeasurementsCOVID-19 cases and severity (hospitalization, intensive care, death). ResultsOf 16,056 PWH in care, 649 were diagnosed with COVID-19 between March-December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized and 12 died. PWH with current CD4 count <350 cells/mm3 (aRR 2.68; 95%CI 1.93-3.71; P<.001) or lowest recorded CD4 count <200 (aRR 1.67; 95%CI 1.18-2.36; P<.005) had greater risk of hospitalization. HIV viral load suppression and antiretroviral therapy (ART) status were not associated with hospitalization, although the majority of PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared to other racial/ethnic groups (aRR 1.51; 95%CI 1.04-2.19, P=.03). Chronic kidney disease (CKD), chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher risk of hospitalization. PWH who were older, not on ART, with current CD4 <350, diabetes, and CKD were overrepresented amongst PWH who required intubation or died. LimitationsUnable to compare directly to persons without HIV; underestimate of total COVID-19 cases. ConclusionsPWH with CD4 <350 cells/mm3, low CD4/CD8 ratio, and history of CD4 <200, have a clear excess risk of severe COVID-19, after accounting for comorbidities also associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination, early treatment, and monitored closely for worsening illness.