ABSTRACT
Background: A SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.
Subject(s)
COVID-19 , Fever , Encephalomyelitis, Acute DisseminatedABSTRACT
Introduction: Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity is insufficient. This study aimed to evaluate anti-spike immunoglobulin G (IgG) titers in the health care workers after the third BNT162b2 vaccination. Methods: Dynamics of anti-spike IgG titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations between anti-spike IgG titer, baseline characteristics, and adverse reactions were also evaluated. Results: The geometric mean titer of anti-spike IgG one month after the third vaccination was 17400 AU/ml, which increased to approximately 30 times immediately before the third vaccination and approximately twice that one month after the second vaccination. In addition, participants with anti-spike IgG titers less than 10000 AU/ml after the second vaccination tended to have higher increases in ant-spike IgG titers before and after the third vaccination. The decline rate of anti-spike IgG was significantly slower after the third vaccination as 35.7% than that after the second vaccination as 59.1%. The anti-spike IgG titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the vaccination showed significantly higher anti-spike IgG titer than those without a headache. Conclusions: The anti-spike IgG induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the anti-spike IgG with a slower decline rate.
Subject(s)
COVID-19 , Headache , Addison DiseaseABSTRACT
Introduction: The administration of a third vaccine is ongoing in many countries, but the evaluation of vaccine-induced immunity is still insufficient. This study evaluated anti-spike IgG levels in 373 health care workers six months after the BNT162b2 vaccination. Methods: Dynamics of anti-spike IgG levels six months after the 2nd vaccination were assessed in 49 participants (Analysis-1). A cross-sectional assessment of anti-spike IgG level was performed in 373 participants (Analysis-2). Participants positive for anti-nucleocapsid IgG or IgM and receiving immunosuppressants were excluded from Analysis-2. Results: In Analysis 1, the median anti-spike IgG level was lower in the older age group and decreased consistently after the second vaccination regardless of age. In Analysis-2, the anti-spike IgG level was significantly negatively associated with age (r = -0.35, p < 0.01). This correlation remained statistically significant (r = -0.28, p < 0.01) even after adjusting for sex, BMI, smoking habits, alcohol drinking habits, allergies, and the presence of fever or other adverse reactions at the time of the vaccination. Alcohol drinking habit was also associated with the anti-spike IgG level; daily alcohol drinkers had significantly lower anti-spike IgG levels than never alcohol drinkers. Sex, smoking habit, allergy, and fever and other side effects after the vaccination were not associated with anti-spike IgG levels six months after the 2nd vaccination. Conclusions: Six months after the vaccination, the anti-spike IgG level was substantially low among older persons and daily alcohol drinkers.
Subject(s)
COVID-19 , Fever , Drug HypersensitivityABSTRACT
During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, that to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here we demonstrate that two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. These mutations reinforce the affinity to viral receptor ACE2, and notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic.
ABSTRACT
Background: The Pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has critically impacted the spread of infection within nursing facilities. We evaluated the usefulness of genetic and serological tests conducted during a COVID-19 outbreak in a nursing facility in Japan.Methods: After the first identification of SARS-CoV-2 infection, a comprehensive, facility- and/or unit-wide PCR testing from nasopharyngeal swabs was repeatedly performed in a three-unit facility including 99 residents with dementia and 53 healthcare personnel. Additionally, PCR testing was conducted separately for residents and staff with fever of ≥37.5 oC. Facility-wide serological testing, including rapid kit testing and quantitative assay, was conducted twice over 1 month apart.Results: A total of 322 PCR and 257 antibody tests were performed. 37 (24.3%) of the 152 individuals (25/99 residents, 25.3%; 12/53 staff, 22.6%) were identified as PCR-positive. Seven residents died with a mortality of 7.1% (7/99). Among the 37 individuals, 10 (27.0%) were asymptomatic at the time of testing. PCR positivity was concentrated on one unit (Unit 1) (20/30 residents, 66.7%; 9/14 staff, 64.3%). The other units showed a limited spread of infection. In unit-wide and separate tests, PCR positivity detection was highly prevalent (22.9% and 44.4%, respectively) in Unit 1, compared with that in the other units. Serological testing identified two additional infected residents with a negative PCR result and showed that no staff was newly identified as infected.Conclusions: Thorough PCR testing, in combination with comprehensive and separate tests, is critical for managing COVID-19 outbreaks in nursing facilities, particularly, in units considered an epicenter. Serological testing is also beneficial for tracing contacts, confirming the number of infected individuals, and authorizing the termination of the outbreak.