Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS)

Abstract

Background We studied humoral responses after COVID-19 vaccination across varying causes of immunodeficiency. Methods Prospective study of fully-vaccinated immunocompromised adults (solid organ transplant (SOT), hematologic malignancy, solid cancers, autoimmune conditions, HIV infection) versus non-immunocompromised healthcare-workers (HCW). The primary outcome was the proportion with a reactive test (seropositive) for IgG to SARS-CoV-2 receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results 1271 participants enrolled: 1,099 immunocompromised and 172 HCW. Compared to HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (p<0.01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus mRNA-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines, after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r=0.89, p<0.0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusion Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCW. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States

“…breakthrough) SARS-CoV-2 infection. 4-9 Our prior study showed a 28% increased risk for breakthrough SARS-CoV-2 infection in PWH compared to people without HIV (PWoH), although breakthrough cumulative incidence was low (PWH=3.1%, PWoH=2.5%), consistent with findings among people with other immunosuppressive conditions. 4,5,9 Data on breakthrough COVID-19 illness, particularly severe illness requiring hospitalization, in PWH remain sparse 10,11…”

“…[4][5][6][7][8][9] Our prior study showed a 28% increased risk for breakthrough SARS-CoV-2 infection in PWH compared to people without HIV (PWoH), although breakthrough cumulative incidence was low (PWH=3.1%, PWoH=2.5%), consistent with findings among people with other immunosuppressive conditions. 4,5,9 Data on breakthrough COVID-19 illness, particularly severe illness requiring hospitalization, in PWH remain sparse 10,11 Studies on the severity of breakthrough COVID-19 illness by HIV status are equivocal, some finding comparable severity, [12][13][14][15] while others have reported a higher risk of developing severe illness and worse outcomes, including death, for PWH compared to PWoH. [16][17][18][19] Immune dysfunction is believed to increase severe COVID-19 illness risk in PWH, with lower CD4 counts and detectable HIV viral loads associated with worse outcomes.…”

People with HIV receiving suppressive antiretroviral therapy show typical antibody durability after dual COVID-19 vaccination, and strong third dose responses

“…While antiretroviral therapy can reverse HIV-induced immune dysfunction to a large extent [13-16], persistent HIV-related immunopathology can nevertheless blunt vaccine responses [17-19], prompting initial concern that PLWH may respond sub-optimally to COVID-19 immunization. Data from clinical trials [20, 21] and real-world studies however [22-27], including from our group [28], described strong initial immune responses to two-dose COVID-19 vaccination in PLWH with controlled HIV loads on therapy and preserved CD4+ T-cell counts [20-24, 28], though weaker responses have been observed in PLWH who are not receiving therapy or who have CD4+ T-cell counts <200 cells/mm 3 [22, 25-27].…”

Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination

“…SARS‐CoV‐2 infection causes substantial morbidity and mortality in solid organ transplant recipients (SOTRs). 1 , 2 , 3 , 4 Vaccination holds promise to reduce COVID‐19 severity in SOTRs, but a significant subset does not develop antibody response after two‐ and three‐dose mRNA vaccine series, 5 , 6 , 7 , 8 which likely contributes to higher rates of COVID‐19 breakthrough after vaccination. 4 Heterologous vaccination (“mixing platforms”) is one potential mode to augment aspects of immune sero‐response, 9 , 10 , 11 , 12 but data are limited in SOTRs.…”