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.
Objective COVID-19 disproportionately impacts residents in long-term care facilities. Our objective was to quantify the presence and magnitude of antibody response in vaccinated, older adult residents at assisted living, personal care, and independent living communities. Design A cross-sectional quality improvement study was conducted March 15 – April 1, 2021 in the greater Pittsburgh region. Setting and Population: Participants were older adult residents at assisted living, personal care, and independent living communities, who received mRNA-based COVID-19 vaccine. Conditions that impair immune responses were exclusionary criteria. Methods Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels, and blinded evaluation of SARS-CoV-2 pseudovirus neutralization titers. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis evaluated relationships between factors potentially associated with antibody levels. Spearman correlations were calculated between antibody levels and neutralization titers. Results All participants (N = 70) had received two rounds of vaccination and were found to have antibodies with wide variation in relative levels. Antibody levels trended lower in males, advanced age, current use of steroids, and longer length of time from vaccination. Pseudovirus neutralization titer levels were strongly correlated ( P < .001) with Beckman Coulter antibody levels (D614 G NT50, r s = 0.91; B.1.1.7 [UK] NT50, r s = 0.91). Conclusions and Implications Higher functioning, healthier, residential older adults mounted detectable antibody responses when vaccinated with mRNA-based COVID-19 vaccines. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects remain to be determined in larger studies as clinical protection is afforded by ongoing adaptive immunity, which is known to be decreased in older adults. This study provides important preliminary results on level of population risk in older adult residents at assisted living, personal care, and independent living communities to inform reopening strategies, but are not likely to be translatable for residents in nursing homes.
Objectives: Immunocompromised patients were excluded from COVID-19 vaccine clinical trials. The objectives of the study were to measure antibody responses, levels, and neutralization capability after COVID-19 vaccination among immunocompromised patients and compare these variables to those of immunocompetent healthcare workers. Methods This is an interim analysis of an ongoing observational, prospective cohort study which launched on April 14, 2021 across Western Pennsylvania. Participants were healthy healthcare workers (HCW) and immunocompromised patients who had completed their COVID-19 vaccination series. Individuals with a history of COVID-19 were not eligible. Serum was collected to measure for the presence of IgG against the SARS-CoV-2 Spike protein using a semi-quantitative assay; antibody levels were available for comparisons. A quasi-random subset of patients was selected for pseudovirus neutralization assays. Seropositivity with 95% Clopper-Pearson exact confidence intervals and distribution of antibody levels were measured. To identify risk factors for seronegativity, clinical characteristics were univariately compared between antibody reactive and non-reactive individuals within the immunocompromised group. Results: 107 HCW and 489 immunocompromised patients were enrolled. Compared to HCWs, seropositivity was significantly lower (p<.001) among immunocompromised patients with Solid organ transplant (SOT), autoimmune, hematological malignancies, and solid tumors (HCW=98.1%; SOT=37.2%; autoimmune=83.8%; hematological malignancies=54.7%; and solid tumor=82.4%, p < 0.05). Over 94% of patients with Human Immunodeficiency Virus were seropositive. Among seropositive patients, antibody levels were much lower among SOT (4.5 [2.1,13.1], p=.020). Neutralization titers tightly correlated with antibody levels (Spearman r = 0.91, p < 0.0001). Conclusion: Our findings demonstrate the heterogeneity of the humoral immune response to COVID-19 vaccines based on underlying immunosuppressive condition and highlight an urgent need to optimize and individualize COVID-19 prevention in these patients. These findings also have implications on public health guidance, particularly given revised Centers for Disease Control and Prevention recommendations permitting vaccinated individuals to abandon masking and social distancing in most settings. Future studies are warranted to determine assessment of cellular immunity, longitudinal measurement of immune responses, and the safety and efficacy of revaccination.
Objective COVID-19 disproportionately impacts older adults residing at long-term care facilities. Data regarding antibody response to COVID-19 vaccines in this population is limited. Our objective was to quantify the presence and magnitude of antibody response in older, vaccinated residents at assisted living, personal care, and independent living facilities. Design A cross-sectional quality improvement study was conducted March 15-April 1, 2021 in the Pittsburgh region. Setting and Population Participants were volunteers at assisted living, personal care, and independent living facilities, who received mRNA COVID-19 vaccine. Conditions that obviate immune responses were exclusionary criteria. Methods Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis were performed to evaluate relationships between factors potentially associated with antibody levels. Results All participants (N=70) had received two rounds of vaccination for COVID-19 and were found to have antibodies to SARS-CoV-2. There was wide variation in relative levels of antibodies as determined by extinction coefficients. Antibody levels trended lower in male sex, advanced age, steroid medications, and longer length of time from vaccination. Conclusions and Implications Higher functioning long-term care residents mounted detectable antibody responses when vaccinated with COVID-19 mRNA-based vaccines. This study provides preliminary information on level of population risk of assisted living, personal care, and independent living residents which can inform reopening strategies. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects of such vaccination programs remain to be determined in larger studies. Clinical protection is afforded not just by pre-formed antibody levels, but by ongoing adaptive immunity, which is known to be decreased in older individuals. Thus, the implications of these levels of antibodies in preventing COVID-19 disease must be determined by clinical follow-up.
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