Association between Sex, Age and Previous COVID-19 Infection with the Risk of Self-Reported Symptoms after Anti-SARS COV-2 mRNA BNT162b2 Vaccination: Data from 3,078 Health Care Workers

Background: Health care workers (HCW) are at high risk of get infected by SARS CoV-2 and thus they are a priority for vaccination.  We hereby aim to investigate whether the risk of severe and moderate systemic symptoms (MSS) after vaccination is higher in HCWs with a history of previous COVID-19.   Methods: An online questionnaire was offered to all HCW undergoing anti-SARS CoV-2 mRNA BNT162b2 vaccine. Previous SARS-CoV-2 infection/COVID-19 was recorded. Local and systemic symptoms after each of the two doses were reported.  MSS were those either interfering with daily activities or resulting in time off-work. Factors associated to MSS were identified by logistic regression. Findings: 3,078 HCW were included. Previous SARS-CoV-2 infection/COVID-19 occurred in 396 subjects (12·9%). 59·6% suffered from >=1 local or systemic symptom after the first and 73·4% after the second dose. MSS occurred in 6·3% of cases (14·4% with previous vs 5·1% with no COVID-19 p<.001) and in 28·3% (24·5% in COVID-19 vs 28·3% no COVID, p=0·074) after the first and second dose. Subjects already experiencing COVID-19 had an independent 3-fold higher risk of MSS after the first and a 30% lower risk after the second dose. Females and younger subjects were at higher risk. No serious adverse events were reported.  Interpretation: Possible differences in immune reactivity are drivers of MSS among females, younger and previously infected HCWs. Vaccination strategies according to previous COVID-19 along with data on the longevity of immune response need to be further investigated.  Funding: None Declaration of Interests: None of the authors have any conflicts of interest to disclose. Ethics Approval Statement: The protocol was approved by the Ethic Committee Area 1, Milan.