Adverse events following COVID-19 vaccination in young Japanese people: A case-control study of the risk of systemic adverse events by a questionnaire surveyShort title: COVID-19 vaccine adverse events in young Japanese

What is known and objectiveRacial differences in adverse events following COVID-19 vaccines have not been sufficiently studied. Here, we aimed to study the adverse events of Modernas intramuscular COVID-19 vaccine in young Japanese people. MethodsA case-control study was conducted using a questionnaire survey. Risk factors were determined using a multivariable logistic regression model. We also compared the occurrence of systemic adverse events in three pairs (minor and adult; male and female; and occurrence and non-occurrence of adverse events after the first dose). Propensity matching was used to balance variables. ResultsWe analysed 3,369 data points (1,877 after the first dose and 1,492 after the second dose) obtained from a questionnaire survey of 7,965 vaccinated individuals. Comparing the results of the first and second doses, the incidence of local adverse events did not change significantly; however, the incidence of systemic adverse events increased significantly (p < 0.001). Eighty-three percent of the participants complained of local adverse events, and 65% of participants complained of systemic adverse events. Anaphylaxis occurred in one female student (0.03%). Even when an adverse event occurred, most of the symptoms improved within 3 days. Female sex was associated with systemic adverse events after the first and second doses with odds ratios (ORs) (95% confidence interval, CI) of 2.49 (2.03-3.06), and 1.83 (1.28-2.61), respectively. Age (<20 years: minor) was associated with systemic adverse events after the first dose with an OR of 1.80 (1.44-2.24). The results of the analysis of six cohorts that were created using propensity score matching showed that the incidence of systemic adverse events at the first dose in females was significantly higher than that in males, and that of minors was significantly higher than that of adults. What is new and conclusionThe results of this study clarified, for the first time, the risk factors for several adverse events from the injection of Modernas intramuscular COVID-19 vaccine in young Japanese people. This study suggests that women, minors who experienced adverse events after the first dose, those who experienced adverse events after the first dose, and those who had adverse events after the second dose, should be aware of adverse events. What is known and objectiveThe COVID-19 crisis has been spreading worldwide, and the number of infected people is increasing due to the emergence of mutant strains. The COVID-19 vaccine is expected to be effective in preventing coronavirus infection and disease aggravation. In Japan, priority groups, such as healthcare workers and the older adults (aged 65 and over), were the first to be vaccinated. Workplace vaccinations began on 21 June 2021 at universities and businesses; university employees and students have also been vaccinated. In June 2021, in Japan, Modernas intramuscular injection of the COVID-19 vaccine was used for vaccination in places associated with students and corresponding teaching staff. However, as of September 2021, the Comirnaty intramuscular injection vaccine had been used for healthcare workers and elderly people ahead of other COVID-19 vaccines. Adverse events of the Comirnaty intramuscular injection vaccine in healthcare workers and elderly people and that of Modernas intramuscular COVID-19 vaccine in the defence forces, who were prioritised for administration, are currently being studied. However, adverse events associated with the intramuscular injection of Modernas COVID-19 vaccine in young people have not yet been well studied in Japan. 1,2. In addition, racial differences in adverse events following coronavirus vaccines have not been sufficiently studied. We have already reported adverse events associated with the first dose of Modernas intramuscular injection of its COVID-19 vaccine. In Japan, the intramuscular injection of Modernas COVID-19 vaccine will continue to be used in large-scale inoculation venues such as universities and workplaces. Therefore, to clarify the adverse events following coronavirus vaccination in the young Japanese population, we conducted a questionnaire survey after the second dose for students, faculty, and staff who belong to an educational foundation, Kyushu Bunka Gakuen.

Adverse events following COVID-19 virus vaccination in Japanese young population: The first cross-sectional study conducted by a questionnaire survey after the first-time-injection

A cross-sectional study was conducted to clarify the adverse events of COVID-19 vaccines in Japanese young population. The proportion of participants with adverse events at the vaccination site (immediately or within 30 minutes after vaccination) was 0.5%, and anaphylaxis occurred in one female student (0.03%). We analyzed 1,877 data obtained from a questionnaire survey of 1,993 vaccinated individuals. Eighty-two percent of participants complained of local adverse events. Injection site pain was the most common local adverse event (71%). Systemic adverse events occurred in 48% of participants. The most common adverse event was myalgia (34%). A multivariable logistic regression model was used to determine risk factors. Local adverse events were associated with sex (female) and allergy history, with odds ratios (ORs) (95% confidence interval [CI]) of 2.15 (1.69-2.73) and 1.73 (1.10-2.74), respectively. Systemic adverse events were associated with sex (female), age (<20 years old), allergy history, and history of adverse events with previous medications, with ORs (95% CI) of 2.49 (2.03-3.06), 1.80 (1.44-2.24), 1.39 (1.03-1.89), and 1.53 (1.02-2.29). The results of this study clarified for the first time that age less than 20 years is a risk factor for systemic adverse events from the COVID-19 Vaccine Moderna Intramuscular Injection. This information will give impacts on considering adverse events and its mechanisms in mRNA vaccination.

MARCH8 targets cytoplasmic lysine residues of various viral envelope glycoproteins

The host transmembrane protein MARCH8 is a RING finger E3 ubiquitin ligase that downregulates various host transmembrane proteins, such as MHC-II. We have recently reported that MARCH8 expression in virus-producing cells impairs viral infectivity by reducing virion incorporation of not only HIV-1 envelope glycoproteins but also vesicular stomatitis virus G-glycoprotein through two different pathways. However, the MARCH8 inhibition spectrum remains largely unknown. Here, we investigate the antiviral spectrum of MARCH8 using HIV-1 pseudotyped with a variety of viral envelope glycoproteins. Pseudotyping experiments revealed that viral envelopes derived from the rhabdovirus, arenavirus, coronavirus, and togavirus (alphavirus) families were sensitive to MARCH8-mediated inhibition. Lysine mutations at the cytoplasmic tails of rabies virus-G, lymphocytic choriomeningitis virus glycoproteins, SARS-CoV and SARS-CoV-2 spike proteins, and Chikungunya virus and Ross River virus E2 proteins conferred resistance to MARCH8. Immunofluorescence showed impaired downregulation of the mutants of these viral envelopes by MARCH8, followed by lysosomal degradation, suggesting that MARCH8-mediated ubiquitination leads to intracellular degradation of these envelopes. Indeed, rabies virus-G and Chikungunya virus E2 proteins proved to be clearly ubiquitinated. We conclude that MARCH8 has inhibitory activity on a variety of viral envelope glycoproteins whose cytoplasmic lysine residues are targeted by this antiviral factor.