ABSTRACT
Background: Most cohorts show similar or lower COVID-19 incidence among people living with HIV (PLWH) compared to the general population. However, incidence may be impacted by lower testing rates among vulnerable populations. We compared SARS-CoV-2 IgG seroprevalence, disease severity, and neutralizing antibody activity after infection among people with and without HIV receiving care within a county hospital system over a three-month period.Methods: From August through October 2020, remnant serum samples were collected from all PLWH who underwent routine outpatient laboratory testing in a municipal healthcare system which houses a large HIV clinic. Patients with HIV were date-of-collection and age-matched (same day, +/- 5 years respectively) to adults without HIV. SARS-CoV-2 IgG and neutralizing antibody titers were measured in serum. Severe disease was assessed by chart review.Findings: Overall, 2,256 samples from 955 PLWH and 1062 people without HIV were tested. Among PLWH, the seroprevalence was 3.7% as compared to 7.4% among people without HIV (adjusted odds ratio (AOR) 0·48; 95% Confidence Interval (CI): 0·34; 0·71). Among those with evidence of prior infection (IgG or PCR), the odds of severe disease were more than 5-fold higher among PLWH (OR 5·13 95% CI: 1·05; 38·9). Among those with past infection, SARS-CoV-2 IgG levels were 45% lower among PLWH vs. those without HIV (95% CI: 22%; 61%); neutralizing antibody titers were 63% lower among PLWH (2%-78%).Interpretation: Among PLWH, there were approximately 50% lower odds of past SARS-CoV-2 infection, possibly due to greater non-pharmaceutical intervention adherence among a population with experience of the HIV epidemic. However, in spite of fewer infections, PLWH experienced more cases of severe disease. Among PLWH with past SARS-CoV-2 infection, lower neutralizing antibody titers were observed and may lead to increased risk of severe COVID-19 disease or reinfection. PLWH should be followed after vaccination to ensure they mount and maintain sufficient responses.Funding Statement: This work was funded by NIH/NIAID R01AI158013.Declaration of Interests: MAS, DVG, TJH, MG, and LBB report funding from the NIH during conduct of the study. DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors have nothing to declare. Ethics Approval Statement: As only remnant samples were used, the University of California, San Francisco IRB did not require informed consent for study participation.The UCSF IRB # is 20-30387.
Subject(s)
HIV Infections , Fibrous Dysplasia, Polyostotic , Encephalitis, Arbovirus , Hallucinations , COVID-19ABSTRACT
Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.
Subject(s)
COVID-19ABSTRACT
Serosurveillance provides a unique opportunity to quantify the proportion of the population that has been exposed to pathogens. Here, we developed and piloted Serosurveillance for Continuous, ActionabLe Epidemiologic Intelligence of Transmission (SCALE-IT), a platform through which we systematically tested remnant samples from routine blood draws in two major hospital networks in San Francisco for SARS-CoV-2 antibodies during the early months of the pandemic. Importantly, SCALE-IT allows for algorithmic sample selection and rich data on covariates by leveraging electronic medical record data. We estimated overall seroprevalence at 4.2%, corresponding to a case ascertainment rate of only 4.9%, and identified important heterogeneities by neighborhood, homelessness status, and race/ethnicity. Neighborhood seroprevalence estimates from SCALE-IT were comparable to local community-based surveys, while providing results encompassing the entire city that have been previously unavailable. Leveraging this hybrid serosurveillance approach has strong potential for application beyond this local context and for diseases other than SARS-CoV-2.
ABSTRACT
Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.
Subject(s)
COVID-19 , DeathABSTRACT
Background The laboratory-based methods to measure the SARS-CoV-2 humoral response include virus neutralization tests (VNTs) to determine antibody neutralization potency. For ease of use and universal applicability, surrogate virus neutralization tests (sVNTs) based on antibody-mediated blockage of molecular interactions have been proposed. Methods A surrogate virus neutralization test established on a label-free immunoassay platform (LF-sVNT). The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies in serum. Results The LF-sVNT neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113), as well as the IgG concentrations and the IgG avidity indices. Although there is variability in the kinetics of the IgG concentrations and neutralizing antibody titers between individuals, there is an initial rise, plateau and then in some cases a gradual decline at later timepoints after 40 days post-symptom onset. The IgG avidity indices, in the same cases, plateau after the initial rise and did not show a decline. Conclusions The LF-sVNT can be a valuable tool in clinical laboratories for the assessment of the presence of neutralizing antibodies to COVID-19. This study is the first to provide longitudinal neutralizing antibody titers beyond 200 days post-symptom onset. Despite the decline of IgG concentration and neutralizing antibody titer, IgG avidity index increases, reaches a plateau and then remains constant up to 8 months post-infection. The decline of antibody neutralization potency can be attributed to the reduction in antibody quantity rather than the deterioration of antibody avidity, a measure of antibody quality. Summary A surrogate virus neutralization test established on a label-free immunoassay platform (LF-sVNT). Using the LF-sVNT and other assays, 246 serum samples from 113 COVID-19 patients were measured. We observed the time course of antibody characteristics beyond 200 days post-symptom onset.
Subject(s)
COVID-19ABSTRACT
The kinetics of IgG avidity maturation during SARS-CoV-2 infection was studied. The IgG avidity assay used a novel label-free immunoassay technology. It was found that there was a strong correlation between IgG avidity and days since symptom onset, and peak readings were significantly higher in severe than mild disease cases.