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      Subjects who developed SARS-CoV-2 specific IgM after vaccination show a longer humoral immunity and a lower frequency of infection

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          Abstract

          Background

          We have previously shown that eliciting SARS-CoV-2-specific IgM after vaccination is associated with higher levels of SARS-CoV-2 neutralizing IgG. This study aims to assess whether IgM development is also associated with longer-lasting immunity.

          Methods

          We analysed anti-SARS-CoV-2 spike protein IgG and IgM (IgG-S, IgM-S), and anti-nucleocapsid IgG (IgG-N) in 1872 vaccinees at different time points: before the first dose (D1; w0), before the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; moreover, 109 subjects were further tested at the booster dose (D3, w44), at 3 weeks (w47) and 6 months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels.

          Findings

          In subjects who had no evidence of a previous infection at D1 (non-infected, NI), IgM-S development after D1 and D2 was associated with higher IgG-S levels at short (w6, p < 0.0001) and long (w29, p < 0.001) follow-up. Similar IgG-S levels were observed after D3. The majority (28/33, 85%) of the NI subjects who had developed IgM-S in response to vaccination did not experience infection.

          Interpretation

          The development of anti-SARS-CoV-2 IgM-S following D1 and D2 is associated with higher IgG-S levels. Most individuals who developed IgM-S never became infected, suggesting that IgM elicitation may be associated with a lower risk of infection.

          Funding

          “Fondi Ricerca Corrente” and “Progetto Ricerca Finalizzata” COVID-2020 ( doi 10.13039/501100003196, Italian Ministry of Health; ); FUR 2020 Department of Excellence 2018–2022 ( doi 10.13039/501100003407, MIUR; , Italy); the Brain Research Foundation Verona.

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          Most cited references30

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          Antibody responses to SARS-CoV-2 in patients with COVID-19

          We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
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            Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction.

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              Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection

              Background The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. Methods We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. Results Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 97% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer–BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) — considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. Conclusions Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050 .)
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                Author and article information

                Journal
                eBioMedicine
                EBioMedicine
                eBioMedicine
                The Author(s). Published by Elsevier B.V.
                2352-3964
                14 February 2023
                March 2023
                14 February 2023
                : 89
                : 104471
                Affiliations
                [a ]Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (Verona), Italy
                [b ]Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
                [c ]Department of Diagnostics and Public Health, University of Verona, Verona, Italy
                [d ]Health Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (Verona), Italy
                Author notes
                []Corresponding author.
                [e]

                Equally contributing.

                Article
                S2352-3964(23)00036-1 104471
                10.1016/j.ebiom.2023.104471
                9925293
                36796232
                af0fb5ab-548b-4fbd-8640-9f2af2369386
                © 2023 The Author(s)

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 October 2022
                : 25 January 2023
                : 25 January 2023
                Categories
                Articles

                sars-cov-2,covid-19,btn162b2 vaccine,igg,igm,spike,breakthrough infection

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