Humoral anti-SARS-CoV-2 immune response after two doses of Comirnaty vaccine in nursing home residents by previous infection status.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality in older adults. Although the advent of the first vaccines has significantly reduced these rates, data on older adults in clinical trials are scarce. OBJECTIVES: We quantified and compared the humoral response in individuals with vs. without pre-existing seropositivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in a cohort of 69 patients living in a nursing home and who had received the recommended two doses of the Comirnaty (Pfizer-BioNTech®) vaccine. RESULTS: All 69 patients (100%) tested positive for antibodies against SARS-CoV-2 at 2 months post-vaccination. Residents with a pre-vaccination infection had significantly higher titers of anti-spike 1 IgG than those with no prior infection (median [interquartile range]: 55,726 [14463-78852] vs. 1314 [272-1249] arbitrary units, respectively; p < 0.001). The same result was observed for neutralizing antibodies titers (704 [320-1280] vs. 47 [20-40] respectively; p < 0.001). Between the pre-vaccination and post-vaccination periods, for IgG and neutralizing antibodies, we observed a 49 and 8-fold increase respectively. In comparison to the wild-type Receptor Binding Domain (RBD), the binding capacity of these vaccine sera was significantly decreased on the B.1.351 and P.1 variants RBD but not decreased with respect to the B.1.1.7 RBD. Although all nursing home residents developed a humoral response following Comirnaty vaccine, its intensity appeared to depend on the pre-vaccination serological status. CONCLUSION: Our results raise the question of how many doses of vaccine should be administered in older and how long the protection will be effective.

Longitudinal Analysis and Comparison of Six Serological Assays up to Eight Months Post-COVID-19 Diagnosis.

BACKGROUND: There is much data available concerning the initiation of the immune response after SARS-CoV-2 infection, but long-term data are scarce. METHODS: We thus longitudinally evaluated and compared the total and neutralizing immune response of 61 patients to SARS-CoV-2 infection up to eight months after diagnosis by RT-PCR using several commercial assays. RESULTS: Among the 208 samples tested, the percentage of seropositivity was comparable between assays up to four months after diagnosis and then tended to be more heterogeneous between assays (p < 0.05). The percentage of patients with a neutralizing titer decreased from 82% before two months postdiagnosis to 57% after six months. This decrease appeared to be more marked for patients under 65 years old and those not requiring hospitalization. The percentage of serology reversion at 6 months was from 11% with the WANTAI total assay to over 39% with the ABBOTT IgG assay. The neutralizing antibody titers decreased in parallel with the decrease of total antibody titers, with important heterogeneity between assays. CONCLUSIONS: In conclusion, serological tests show equivalent sensitivity in the first months after the diagnosis of SARS-CoV-2 infection, but their performance later, postinfection, must be considered when interpreting the results.

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals.

A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.