One dose of SARS-CoV-2 vaccine exponentially increases antibodies in individuals who have recovered from symptomatic COVID-19

Abstract

BACKGROUNDThe COVID-19 vaccines currently in use require 2 doses to achieve optimal protection. Currently, there is no indication as to whether individuals who have been exposed to SARS-CoV-2 should be vaccinated, or whether they should receive 1 or 2 vaccine doses.METHODSWe tested the antibody response developed after administration of the Pfizer/BioNTech vaccine in 124 health care professionals, of whom 57 had a previous history of SARS-CoV-2 exposure with or without symptoms.RESULTSPostvaccine antibodies in SARS-CoV-2-exposed individuals increased exponentially within 5 to 18 days after the first dose compared to naive subjects (P < 0.0001). In a multivariate linear regression (LR) model we showed that the antibody response depended on the IgG prevaccine titer and on the exposure to SARS-CoV-2. In symptomatic SARS-CoV-2-exposed individuals, IgG reached a plateau after the second dose, and those who voluntarily refrained from receiving the second dose (n = 7) retained their antibody response. Gastrointestinal symptoms, muscle pain, and fever markedly positively correlated with increased IgG responses. By contrast, all asymptomatic/paucisymptomatic and unexposed individuals showed an important increase after the second dose.CONCLUSIONOne vaccine dose is sufficient in symptomatic SARS-CoV-2-exposed subjects to reach a high titer of antibodies, suggesting no need for a second dose, particularly in light of current vaccine shortage.TRIAL REGISTRATIONClinicalTrials.gov NCT04387929.FUNDINGDolce & Gabbana and the Italian Ministry of Health (Ricerca corrente).

Keywords: Adaptive immunity; Immunoglobulins; Immunology; Vaccines.

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1. Experimental design.

Observational study approved by the international review board of Istituto Clinico Humanitas (ClinicalTrials.gov NCT04387929). Accrual was on a voluntary basis. All participants signed an informed consent and completed a questionnaire indicating a previous history of SARS-CoV-2 exposure and COVID-19–associated symptoms/clinical manifestations (SARS-CoV-2-Exp). This study was conducted at Istituto Clinico Humanitas in which health care and administrative staff were followed for serology before (Pre VAX), after the first dose (Post VAX1), and after the second dose (Post VAX2) of the Pfizer/BioNTech vaccine.

Figure 2. Exponential increase of anti-Spike 1/2 IgG levels after the first dose of vaccine in SARS-CoV-2–exposed subjects.

(A) Anti-Spike 1/2 IgG plasma levels before (Pre VAX), after the first dose (Post VAX1) or after the second dose (Post VAX2) of vaccine in naive (Pre VAX, Post VAX1 [n = 67], Post VAX2 [n = 64]) and SARS-CoV-2–exposed individuals (SARS-CoV-2-Exp; Pre VAX [n = 46], Post VAX1 [n = 57], Post VAX2 [n = 47]). Each dot corresponds to an individual subject. Log scale on y axis. (B) Anti-Spike 1/2 IgG plasma levels in naive (n = 64) and SARS-CoV-2–exposed individuals (n = 36). Spaghetti plot showing the trends for each individual subject by linked dots. Log scale on y axis. (C) Association between the log-transformed amount of IgG following the first vaccine dose and the clinical variable through multivariate LR (naive n = 67, SARS-CoV-2–exposed individuals n = 46). The coefficients for the most significant variables (P < 0.05) are reported. Dot points represent the mean values of regression coefficients and lines the 95% CI. (D) Association between the amount of IgG following the second vaccine dose and the clinical variable through multivariate LR (naive n = 64, SARS-CoV-2–exposed individuals n = 36). The coefficients for the most significant variables (P < 0.05) are reported. Dot points represent the mean values of regression coefficients and lines the 95% CI. The box plots (A) show the interquartile range, the horizontal lines show the median values, and the whiskers indicate the minimum-to- maximum range. P values were determined using 2-tailed Kruskal-Wallis test with Dunn’s post test (A) or 2-tailed Wilcoxon matched-pairs signed rank test (B).

Figure 3. Symptomatic SARS-CoV-2–exposed subjects show higher increase of anti-Spike 1/2 IgG levels after the first dose of vaccine.

(A and B) Anti-Spike 1/2 IgG plasma levels in asymptomatics/paucisymptomatics (n = 15) or symptomatics (n = 42) after the first (A) or after the second dose of vaccination (asymptomatics/paucisymptomatics n = 14, symptomatics n = 33) (B). Each dot corresponds to an individual subject. Log scale on Y axis. (C) Before and after plot (asymptomatics/paucisymptomatics n = 14, symptomatics n = 33), showing trends for each individual subject by linked dots. (D and E) Anti-Spike 1/2 IgG plasma levels in symptomatic SARS-CoV-2–exposed individuals (n = 7) at around 12 days (Post Vax1) or around 34 days (Post Vax1 second time point) after the first dose of vaccine (D). Spaghetti plot showing the trends for each individual subject by linked dots (E). Log scale on y axis. The box plots (A, B, and D) show the interquartile range, the horizontal lines show the median values, and the whiskers indicate the minimum-to-maximum range. P values were determined using 2-tailed unpaired Kolmogorov-Smirnov test (A and B) or 2-tailed Wilcoxon matched-pairs signed rank test (symptomatics post VAX1 vs post VAX 2, P < 0.0001; asymptomatics/paucisymptomatics post VAX1 vs post VAX2, P = 0.0001) (C); 1-way ANOVA with Tukey’s post test (D) or 2-tailed paired Student’s t test (E).