Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV (preprint)

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4+ T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV-negative participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV-negative participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4+ T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

COVID Symptoms, Seroprevalence, and Mortality During the First Wave of SARS-CoV-2 in Canada (preprint)

Background: Canada had substantial mortality from COVID in the first SARS-CoV-2 wave, mostly in nursing homes. Efforts to stem the pandemic (including vaccination, now being introduced) can benefit from direct understanding of the relationship of age-specific mortality to SARS-CoV-2 seroprevalence and from information on asymptomatic infection.Methods: The Action to Beat Coronavirus (Ab-C) study surveyed a reasonably representative sample of 19,994 adult Canadians about COVID symptoms and analyzed IgG antibodies against SARS-CoV-2 from self-collected dried blood spots (DBS) in 8,967 adults. A sensitive and specific chemiluminescence ELISA detected IgG to the spike trimer. We compared seroprevalence to deaths to establish infection fatality rates (IFRs) and used mortality data to estimate infection levels in nursing home residents.Findings: The best estimate (high specificity) of adult seroprevalence nationally is 1.7%, but as high as 3.5% (high sensitivity) depending on assay cutoffs. The highest prevalence was in Ontario (2.4-3.9%), the most populous province, and in younger adults aged 18-39 years (2.5-4.4%). Based on mortality, we estimated 13-16% of nursing home residents became infected. The first viral wave infected 0.54-1.08 million adult Canadians, half of whom were <40 years old. The IFR outside nursing homes was 0.20-0.40%, but the COVID death rate in nursing home residents was >70 times higher than comparably-aged adults living in the community. Seropositivity correlated with COVID symptoms, particularly during March. Asymptomatic adults constituted about a quarter of definite seropositives, with a greater proportion in the elderly.Interpretation: Canada had relatively low infection prevalence and low IFRs in the community, but not in nursing homes, during the first viral wave. The Ab-C study demonstrates the practicability of using self-collected DBS for antibody testing in national surveys to monitor the pandemic and vaccine-induced immunity in the population.Funding Statement: Pfizer Global Medical, Unity Health Foundation, Canadian COVID-19 Immunity Task ForceDeclaration of Interests: We declare no competing interests.Ethics Approval Statement: Ethics approval was provided by St. Michael's Institutional ReviewBoard. REB 20-107