key: cord-0702010-o0u7i5rs authors: Tré-Hardy, Marie; Cupaiolo, Roberto; Papleux, Emmanuelle; Wilmet, Alain; Horeanga, Alexandra; Antoine-Moussiaux, Thomas; Vecchia, Andrea Della; Beukinga, Ingrid; Vekemans, Marc; Blairon, Laurent title: Reactogenicity, safety and antibody response, after one and two doses of mRNA-1273 in seronegative and seropositive healthcare workers date: 2021-04-01 journal: J Infect DOI: 10.1016/j.jinf.2021.03.025 sha: c2d2a1c17414b5f7cf0a76237650736e805abb2e doc_id: 702010 cord_uid: o0u7i5rs nan We read with great interest the prospective SARS-CoV-2 serosurveillance study of Harris RJ et al. in 2 your columns 1 . During 6 months and before the UK vaccination campaign, they followed the antibody 3 response in a cohort of 2246 healthcare workers (HCWs). They relied on 4 commercial kits and an in-4 house test to track the antibody response to natural SARS-CoV-2 exposure. As expected with kits that 5 targets different proteins and total or specific immunoglobulin sub-groups, they observed, along time, 6 fluctuating seropositivity from one test to another. Nevertheless, they showed that SARS-CoV-2 7 antibodies do not decline as quickly as predicted by smaller cohorts of patients with shorter follow-up. With the start of worldwide vaccination campaigns, scattered evidence is emerging from the medical 9 literature to dispute the second injection of mRNA vaccines in individuals previously infected with 10 SARS-CoV-2 2,3 . Knowing that a significant proportion of the population would be seropositive at the 11 time of the first injection, we wanted to investigate the utility of a second dose under both supply and 12 time constraints. Here we report our observations in a cohort of healthcare workers (HCWs) who were In our prospective study, we compared not only the antibody response ( Figure 1 ) but also the local 21 and systemic side effects in terms of duration and intensity after the first and second dose of mRNA-22 1273 ( Figure 2 ).The quantitative analysis of the anti-SARS-CoV-2 IgG antibodies directed against the 23 subunits (S1) and (S2) of the virus spike protein was carried out using the LIAISON ® SARS-CoV-2 IgG kit 24 (DiaSorin ® , Saluggia, Italy) on a LIAISON ® XL analyzer previously validated in our laboratory 4 . In order to assess the serological status of the participants (n=160), a first dosage was carried out with a median 1 time (± 95% confidence interval [CI]) of 2 (± 0.29) days before the first injection (T0). Among those, 36 2 participants were found to be seropositive. Two other samples were taken from all participants 2 3 weeks after the first injection (T1) (median time [± 95% CI]: 16 [± 0.25] days), and 2 weeks after the 4 second injection (T2) (median time [± 95% CI]: 14 [± 0.21] days). Except for 2 individuals, all 5 participants who were seropositive at T0, saw their antibody levels boosted by the first dose but no 6 additional boosting effect was observed after the second injection. In these two individuals (1.6%), the 7 second injection made it possible to raise their antibody levels from 59.7 and 105 AU / mL to above 8 the maximum detection limit (> 400 AU / mL) at T2. In seronegative participants, the anti-S antibody 9 titers obtained after a single dose were comparable to those obtained in unvaccinated seropositive 10 participants while the second injection was necessary to achieve higher antibody levels approaching 11 those obtained for seropositive individuals (T1). We also explored the frequency of side effects after 12 the first dose in a slightly larger cohort (n=206, mean age, 48.6 (± 11.6) years) including 151 13 seronegative (71% female) and 55 seropositive participants (69% female), as well as after the second 14 dose in 113 participants (mean age, 49.2 (± 11.3) years) including 89 seronegative participants (69% 15 female) and 24 seropositive participants (58% female). The intensity of local and systemic side effects 16 reported by participants was graded into 4 levels of severity: (very mild, mild, moderate, severe). Common side effects such as articular pain, muscular pain, headache, fatigue, fever, adenopathy and 18 oedema from the first dose appear to be more frequent and severe in previously infected individuals 19 (P < .05). Nevertheless, it seems that the second injection generates a greater overall systemic 20 reaction than that observed after the first one, regardless of the initial serological status of the 21 participants. Seven days after the first or the second dose, all observed side effects disappeared in all 22 participants and none were hospitalized. Two weeks after the last injection, a clinical follow-up 23 questionnaire was sent to the 113 participants. Only 41 were returned at the time of redaction. None 24 of the respondents reported thinking they had been infected. Ten of them had to undergo a RT-qPCR 25 and all were negative. 1 seronegative individuals prior to vaccination, especially when the serological status is easily accessible, 2 as the additional protective effect of the second dose has yet to be demonstrated in these individuals. The determination of the antibody titers after the initial dose could be used in order to catch-up the 4 very few vaccinees with a weaker response. In the worrying context of an increase in the spread of mutant viruses around the world 5 and given 6 that most registered vaccine platforms use the two-dose-prime boost approach 6-8 , this strategy would 7 help speed up vaccination campaigns and achieve group immunization goals more rapidly. Even 8 though titers of antibodies against S1 spike protein seem to correlate with viral neutralization 9 studies 6,9,10 , only long-term serosurveillance studies will not only confirm the results of our 10 investigation but will also determine the IgG protection thresholds. 12 13 14 Acknowledgements: The authors thank all the members of the clinical laboratory staff for technical 1 assistance. We also thank the HCWs who participated in this study. represent outside and far out values. A Mann-Whitney U-test was used to assess the differences in IgG 6 levels between seronegative and seropositive subjects on the one hand and to assess the changes in 7 these levels between T0, T1 and T2 times within each of these groups on the other hand. 8 Fig.2 lists the reported side-effects according to their nature and severity during the first (n=206) and 9 second (n=113) dose administration. The gradation was as follow: absence (green), very mild (yellow), 10 mild (light orange), moderate (dark orange), severe (red). A given participant possibly experienced 11 more than one symptom. A Chi-square test was used for the comparison of side effects in Serological surveillance of SARS-CoV-2: Six-month trends and 4 antibody response in a cohort of public health workers Antibody Responses in Seropositive Persons after a 8 Single Dose of SARS-CoV-2 mRNA Vaccine Antibody response to first BNT162b2 dose in previously 12 SARS-CoV-2-infected individuals Validation of a chemiluminescent assay for specific SARS-CoV-2 15 antibody Joint Committee on Vaccination and Immunisation. Optimising the COVID-19 17 vaccination programme for maximum short-term impact Safety and Efficacy of the BNT162b2 mRNA Covid-19 Roberts Paul 22 C., Makhene Mamodikoe, et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults Safety and efficacy of the ChAdOx1 nCoV-19 vaccine 26 (AZD1222) against SARS-CoV-2: an interim analysis of four randomised Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine 31 Candidates Effect of previous SARS-CoV-2 infection on humoral and T-cell responses 34 to single-dose BNT162b2 vaccine