ABSTRACT
Background: Asymptomatic COVID-19 is common among the general population, but little has been reported on this phenomenon among people with HIV (PWH) globally. Here we present data on a representative subset of 2,464 REPRIEVE participants with blood collected for COVID-19 serology from May 2020 to February 2021. Methods: REPRIEVE is an international primary atherosclerotic cardiovascular disease (ASCVD) prevention RCT of pitavastatin calcium vs. placebo among 7,770 PWH ages 40-75 on antiretroviral therapy (ART). Beginning in April 2020, targeted data on COVID-19 diagnosis and symptoms were collected as part of routine trial visits every 4 months, and blood was collected annually to assess SARS-CoV-2 serology. SARS-CoV-2 infection was defined as either presence of SARS-CoV-2 IgG or IgA RBD protein (anti-spike) antibodies or reporting of confirmed COVID-19 disease prior to the date of antibody sampling in the absence of prior COVID-19 vaccine receipt. We distinguished symptomatic from asymptomatic disease based on completed COVID-19 symptom questionnaire. Demographic, cardiometabolic, and HIV-specific data are described among those with symptomatic versus asymptomatic COVID-19 disease. Results: Participant characteristics (n=2464) included median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm3, and 97% with HIV VL <400 cp/mL. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical disease diagnosis and 260 with reactive Abs but no reported clinical disease. Of these persons, 304 completed symptom questionnaires: 120 (39%) reported at least 1 symptom of COVID-19 disease, but 184 (61%) reported no symptoms. PWH with asymptomatic infection were more likely to be from non-High Income Regions, of Black or African American race, and to be non-obese (Table). Median ASCVD risk score was <5% (low risk) for the two groups. Potential differences in symptomatic disease based on ART-regimen were noted, but no clinical differences between the groups for CD4 counts or HIV viral suppression were observed. Conclusion: Asymptomatic SARS-CoV-2 infection is very common among ART-treated PWH globally. With Ab testing, we determined that 61% of COVID-19 infections were asymptomatic in the REPRIEVE cohort, similar to rates reported in the general population. HIV clinicians must remain vigilant about COVID-19 testing among PWH to assure that asymptomatic cases are identified.
ABSTRACT
Background: SARS-CoV-2 vaccines capable of inducing broad and cross-reactive humoral and T cell responses help to fight against emerging variants. In this study we compared the immunogenicity and efficacy of modified vaccinia Ankara (MVA) based SARS-CoV-2 vaccine expressing furin-cleavage site inactivated stabilized spike (SdFCS) and nucleocapsid (N) delivered via intramuscular (IM), buccal or sublingual (SL) routes in rhesus macaques (RMs). Methods: Three groups (n=5/group) of RMs were immunized with MVA/SdFCS-N vaccine on weeks 0 and 4, via IM, buccal, or SL route. An additional group (control) received non-recombinant MVA via IM. IM vaccinations were delivered using needle and SL and buccal vaccinations were delivered using a needle-free injection device. All RMs were challenged with B.1.617.2 strain (Delta) of SARS-CoV-2 at week 8 via intratracheal and intranasal routes simultaneously. Various humoral and cellular immune parameters were determined post vaccination and challenge. SARS-CoV-2 subgenomic RNA (sgRNA) was measured to monitor virus replication in the upper (nose) and lower (lung) respiratory tract. Results: IM vaccination induced strong RBD-specific IgG antibody in serum, nose, throat, lung, and rectum. The serum antibody showed strong live virus neutralizing activity against WA-1/2020 (median of 415) and B.1.617.2 strains (median of 317). Serum from IM vaccinated animals also demonstrated strong non-neutralizing effector functions such as ADCD, ADCP and ADNKA. In addition, IM vaccination induced strong CD4 and CD8 T cell response in the blood that was directed against both S and N. In contrast, the SL and buccal vaccination-induced antibody showed lower neutralization titer against WA-1/2020 (143 and 302, respectively), and showed 4.5-fold lower cross reactivity neutralization titer against B.1.617.2 compared to WA-1/2020. Following challenge with B.1.617.2, the IM group RMs showed superior protection with 3 of the 5 animals being negative in upper and lower respiratory airways at Day 2. In contrast, no significant protection was observed in the SL group. Vaccine induced neutralizing and non-neutralizing antibody effector functions showed direct association with protection. Conclusion: Our findings showed that IM vaccination with improved MVA-based SARS-CoV-2 vaccine elicits cross-reactive antibody and T cell responses and protect against heterologous SARS-CoV-2 Delta challenge in RMs. They also showed IM vaccinations are superior to oral vaccinations.
ABSTRACT
The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across 0-coronaviruses, we found that the early development of SARS-CoV-2-specific immunity occurred in tandem with preexisting common I3-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.