Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

Background SARS-CoV-2 has disproportionately affected nursing homes (NH). In Ireland, the first NH case COVID-19 occurred on 16/03/2020. A national point-prevalence testing program of all NH residents and staff took place (18/04/2020–05/05/2020). Aims To examine characteristics of NHs across three Irish Community Health Organisations (CHOs), proportions with COVID-19 outbreaks, staff and resident infection rates symptom-profile, and resident case-fatality. Methods Forty-five NHs surveyed requesting details on occupancy, size, COVID-19 outbreak, outbreak timing, total symptomatic/asymptomatic cases, and outcomes for residents from 29/02/2020–22/05/2020. Results Surveys were returned from 62.2% (28/45) of NHs (2043 residents, 2,303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1741 residents, 1972 beds). Median time from first COVID-19 case in Ireland to first case in these NHs was 27.0 days. Resident incidence was 43.9% (764/1741): 40.8% (710/1741) laboratory-confirmed, with 27.2% (193/710) asymptomatic, and 3.1% (54/1741) clinically-suspected. Resident case-fatality was 27.6% (211/764) for combined laboratory-confirmed/clinically-suspected COVID-19. Similar proportions of residents in NHs with “early-stage” (<28 days) versus “later-stage” outbreaks developed COVID-19. Lower proportions of residents in “early” outbreak NHs had recovered compared to those with “late” outbreaks (37.4% vs 61.7%; χ2 = 56.9, P < 0.001). Of 395 NH staff across twelve sites with confirmed COVID-19, 24.7% (99/398) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearman’s rho = 0.81, P < 0.001). Conclusion This study demonstrates the significant impact of COVID-19 on the NH sector. Systematic point-prevalence testing is necessary to reduce risk of transmission from asymptomatic carriers and manage outbreaks in this setting.

Objectives Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. Design Longitudinal cohort study. Setting and Participants Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. Methods Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. Results Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: −0.05; 95% CI: −0.08 to −0.02; P < .001) and frailty (β: −0.22; 95% CI: −0.33 to −0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. Conclusions and Implications In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

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Background Older Nursing Home Residents (NHRs) are at greatest risk of morbidity and mortality from SARS-CoV-2, particularly in the context of both waning vaccine efficacy and the emergence of Variants-of-Concern (VOCs). However, the determinants of long-term vaccine-induced protective antibody responses are yet to be determined in this group. Methods NH-COVAIR recruited older NHRs for comprehensive clinical and frailty (NH-FRAIL) assessment. Blood samples were obtained pre-vaccination, at 6-weeks and 6-months following primary vaccination and 6-months following booster vaccination. Antibody titres were measured using both an electrochemiluminescence assay and a custom bead-based array (Luminex™) to measure antibody titre and avidity for Wuhan strain/major VOC antigens. Stepwise adjusted linear regression (log-transformed) assessed longitudinal determinants of vaccine-induced antibody responses. Results Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%) had evidence of previous SARS-CoV-2 infection. All NHRs mounted a significant antibody-response to vaccination at 5 weeks followed by a significant decrease in antibody titre by 6 months. Previous SARS-CoV-2 infection was the strongest predictor of antibody waning at all timepoints (β: 3.59; 2.89, 4.28; P &lt; 0.001 for 6-months). Independent of infection history, both age (β: –0.05; –0.08, –0.02; p&lt;0.001) and frailty (β: –0.22; –0.33, –0.11; p&lt;0.001) were associated with faster antibody waning at 6-months. Cross-reactivity and avidity were significantly lower for Beta (B.1.351) and Gamma (P.1) VOC strains (all p&lt;0.001). Additionally, there was faster antibody waning and significantly reduced antibody avidity to Beta and Gamma VOCs in SARS-CoV-2 naïve NHRs. Conclusion Older NHRs are capable of mounting protective antibody responses to SARS-CoV-2 vaccination. Responses were more durable, with a greater cross-reactivity to and avidity for VOCs in those with previous SARS-CoV-2 infection. Increasing age and greater frailty in NHRs was associated with faster antibody waning. Our findings support ongoing serological surveillance and use of additional vaccine doses in older NHRs, particularly in those without previous SARS-CoV-2 exposure.