RESUMO
ImportancePublic health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. We present detailed immunological evidence to clarify the requirements for one-or two-dose primary vaccination series for naturally primed individuals. ObjectiveEvaluate the immune response to COVID-19 mRNA vaccines in healthcare workers (HCWs) who recovered from a SARS-CoV-2 infection. DesignMulticentric observational prospective cohort study of HCWs with a PCR-confirmed SARS-CoV-2 infection designed to evaluate the dynamics of T and B cells immune responses to primary infection and COVID-19 mRNA vaccination over 12 months. ParticipantsUnvaccinated HCWs with PCR-confirmed SARS-CoV-2 infection were selected based on the presence or absence of symptoms at infection and serostatus at enrollment. Age- and sex-matched adults not infected with SARS-CoV-2 prior to vaccination were included as naive controls. ExposureVaccination with Pfizer BioNTech BNT162b2 mRNA vaccine. Main Outcome(s) and Measure(s)Immunity score (zero to three), before and after vaccination, based on anti-RBD IgG ratio, serum capacity to neutralize live virus and IFN-{gamma} secretion capacity in response to SARS-CoV-2 peptide pools above the positivity threshold for each of the three assays. We compared the immunity score between groups based on subjects symptoms at diagnosis and/or serostatus prior to vaccination. ResultsNone of the naive participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naive individuals, with significantly weaker responses than those who were symptomatic during infection. Conclusions and RelevanceIndividuals who did not develop symptoms during their initial SARS-CoV-2 infection and were seronegative prior to vaccination present immune responses comparable to that of naive individuals. These findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection. KEY POINTS QuestionIs a single dose of COVID-19 mRNA vaccine sufficient to induce robust immune responses in individuals with prior SARS-CoV-2 infection? FindingsIn this cohort of 55 health care workers previously infected with SARS-CoV-2, we show that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Lack of symptoms and a negative serostatus prior to vaccination leads to immune responses comparable to naive individuals. MeaningOur results support a two-dose primary series requirement for any individual with prior history of asymptomatic SARS-CoV-2 infection.
RESUMO
Background and ObjectivesOlfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals in the first months after the infection. As only few reports have described their prognosis more than 6 months later, the main objective of this study was to assess the prevalence of OD and GD 11 months after COVID-19. We also aimed to determine test-retest reliability of subjective chemosensory ratings for the follow-up of chemosensory sensitivity, as this measure is often used for remote follow-up. MethodsInclusion criteria included a PCR-confirmed SARS-CoV-2 infection; exclusion criteria were the presence of other respiratory infections and chronic sinusitis. To assess whether OD and GD had changed compared to pre-pandemic levels, we designed an observational study and distributed an online questionnaire assessing quantitative chemosensory function to healthcare workers 5 and 11 months after COVID-19. Specifically, we assessed olfaction, gustation, and trigeminal sensitivity (10-point visual analog scale) and function (4-point Likert scale) separately. We further assessed clinically relevant OD using the Chemosensory Perception Test, a psychophysical test designed to provide a reliable remote olfactory evaluation. Qualitative chemosensory dysfunction was also assessed. ResultsWe included a total of 366 participants (mean age of 44.8 years old (SD: 11.7)). They completed the last online questionnaire 10.6 months (SD: 0.7) after the onset of COVID-19 symptoms. Of all participants, 307 (83.9%) and 301 (82.2%) individuals retrospectively reported lower olfactory or gustatory sensitivity during the acute phase of COVID-19. Eleven months later, 184 (50.3%) and 163 (44.5%) indicated reduced chemosensory sensitivity, 32.2% reported impairment of olfactory function while 24.9% exhibited clinically relevant OD. Three variables predicted OD at follow-up, namely chest pain and GD during COVID-19 and presence of phantosmia at 5 months. Olfactory sensitivity ratings had a high test-retest reliability (intraclass correlation coefficient: 0.818 (95% CI: 0.760 - 0.860)) DiscussionThis study suggests that chemosensory dysfunctions persist in a third of COVID-19 patients 11 months after COVID-19. Subjective measures have a high test-retest reliability and thus can be used to monitor post-COVID-19 OD. OD appears to be a common long-term symptom of COVID-19 important to consider when treating patients.
