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      Effectiveness of the severe acute respiratory syndrome coronavirus 2 Omicron BA.5 bivalent vaccine on symptoms in healthcare workers with BA.5 infection

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          Abstract

          Background

          The infection status of healthcare workers (HCWs) with coronavirus disease 2019 has become a major concern worldwide. In this study, we investigated the efficacy of the number of vaccine doses on symptoms after BA.5-adapted bivalent vaccination in HCWs.

          Methods

          We analyzed the occupation, route of infection, symptoms, and vaccination history of all HCWs who tested positive for severe acute respiratory syndrome coronavirus 2 and worked in our hospital from November 2020 to March 2023. A logistic regression analysis was performed to examine the association between the presence of BA.5-adapted bivalent vaccination and symptoms.

          Results

          During the observation period, 531 HCWs became infected. Of these, 72 % were women, with a median age of 30 years. Nurses accounted for 57 % of the infected cases, and many of the infection routes were from family members. We examined the relationship between symptoms in 352 HCWs infected with the Omicron BA.5* variant and the number of vaccine doses. As the number of vaccine doses increased, the rate of fever decreased, while symptoms such as a runny nose and sore throat tended to increase. The logistic regression analysis showed that the rate of fever tended to decrease (odds ratio = 0.52, 95 % confidence interval: 0.26–1.01, p = 0.056) and that of a runny nose increased (odds ratio = 3.68, 95 % confidence interval: 1.17–10.6, p = 0.018) after BA.5-adapted bivalent vaccination.

          Conclusion

          This study shows that fever is reduced and mild symptoms are increased after BA.5-adapted bivalent vaccination in BA.5-infected HCWs. This result highlights the potential effectiveness of tailored vaccination strategies in the management of emerging COVID-19 variants.

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          Most cited references27

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

              The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
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                Author and article information

                Contributors
                Journal
                Vaccine X
                Vaccine X
                Vaccine: X
                Elsevier
                2590-1362
                06 January 2024
                March 2024
                06 January 2024
                : 17
                : 100433
                Affiliations
                [a ]Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
                [b ]Division of Infection Control and Prevention, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
                [c ]Central Clinical Laboratory, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
                [d ]Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
                [e ]The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
                Author notes
                [1]

                These authors contributed equally to this work.

                Article
                S2590-1362(24)00006-8 100433
                10.1016/j.jvacx.2024.100433
                10826328
                38299200
                bb659a2f-83ea-416a-aad0-28076900646d
                © 2024 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 October 2023
                : 14 November 2023
                : 4 January 2024
                Categories
                Regular paper

                covid-19,vaccine,symptom,bivalent,omicron
                covid-19, vaccine, symptom, bivalent, omicron

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