Three Doses of Covid-19 Vaccines in Pwh: Immunogenicity and Effects on Hiv Reservoir

Background: People with HIV (PWH) older than age 55 have an enhanced risk of complications from SARS-CoV-2 infection. It is unclear whether COVID-19 vaccines with a booster are as durable in terms of immunogenicity in this cohort or whether these vaccines can destabilize HIV reservoirs. Method(s): We prospectively studied 91 PWH on cART aged 55 or over (n=91) and 23 age-matched individuals without HIV (control group, CG) who received three doses of COVID-19 vaccines (D1-D3) over 48 weeks. Participants received combinations of BNT162b2, mRNA-1273, and ChAdOx1. Of PWH, 42 were immune responders (IR), 20 were non-responders (INR), and 3 had a low-level viremia (LLV). Total and neutralizing Abs to SARS-CoV-2 spike (S) and RBD in sera and saliva, frequency of anti-RBD/NTD memory B cells (spectral flow cytometry), S-specific T cell immunity (IFN-g, IL-2 ELISpot) and HIV reservoirs in peripheral CD4+ T cells (IPDA) were measured. Result(s): No significant differences in vaccine regimens or dosing intervals were observed between PWH and CG. Vaccines elicited equally strong anti-S IgG in PWH vs CG in serum and saliva, and RBD IgG in serum. Serum Abs peaked at 4w after D3. Week 48 serum IgG in PWH vs CG were 916 vs 919 BAU/ mL for S (p=0.624) and 706 vs 752 for RBD (p=0.198), respectively. Week 48 median saliva S IgG: 48.1% AUC of the positive control in PWH vs 95.9% for CG (p=0.384). S IgA: 3.83 vs 20.5 in PWH vs CG (p=0.039). Median neutralizing titers post-D2 were significantly lower in PWH than in CG (NT50 82.9 vs 535, p< 0.001). However, after D3, at 48w, PWH had similar titers as CG: 309 vs 269 (p=0.745), mirroring an increase in RBD/NTD-specific B cells in PWH. Anti-S T cell cytokine responses were stronger in IR PWH after D2 and D3 than in CG. Week 48 S IL-2 responses: median 135 SFC/106 PBMC vs 43.8 (p< 0.001), but only 12.5 in INR (p=0.001 vs IR). COVID-19 vaccines did not affect the size of HIV reservoir in PWH (change in median frequency of intact proviruses from baseline: 95.0 vs 90.9, p=0.952), except in three LLV PWH (mean increase 93.7% at 48w). Conclusion(s): PWH aged 55 and over show diminished neutralizing Ab responses to SARS-CoV-2 with two vaccine doses which are 'rescued' after a booster. PWH have lower S-specific IgA in saliva after vaccination which may affect protection. Enhanced S-specific T cell immunity in PWH suggests Th1 imprinting from preexistent HIV infection. COVID-19 vaccines did not destabilize the HIV reservoir in most PWH but may pose potential risk in unsuppressed viremia.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Outcomes of Kidney Transplant During the SARS-CoV-2 Pandemic at 1 Center in Poland.

The SARS-CoV-2 pandemic has significantly affected the number of transplanted organs worldwide. The rules and restrictions related to transplantation activities in Poland are included in the updated guidelines of the Polish Organizational and Coordination Centre for Transplantation. Our clinic faces the same problems as the rest of the hospitals in the country. Not only are the number of recipients falling, but there are also numerous restrictions concerning, among other things, qualification of donors and recipients and even preparation of centers for long-term care in the event of infection of organ recipients with the SARS-CoV-2 virus. Statistics showed, after an initial fall in the number of kidneys transplanted, a temporary normalization during the summer months, only to record a fall again with an increase in new cases of COVID-19. A total of 29 kidneys were transplanted at our center between March and December 2020. Kidney transplantation is not only linked to the operation itself, but also to the follow-up care of the recipients. Reduced immunity among recipients due to immunosuppressive treatment as well as comorbidities among recipients contribute to this group being at increased risk of symptomatic SARS-CoV-2 infection. The number of cases of SARS-CoV-2 infection among kidney transplant recipients at our center was 7, of which we recorded 2 deaths due to COVID-19 in the period after kidney transplant. Postoperative complications probably related to previous SARS-CoV-2 infection occurred in 1 patient.