ABSTRACT
Purpose: SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection+vaccination) is affected by the moment of vaccination and the number of doses received. Methods: We conducted a retrospective study in 745 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months and later, and comparing one, two or three doses(incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Results: The tRI was significantly higher in those vaccinated vs. non-vaccinated (q<0.001). However, an early incomplete regime(1 dose) protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime(q<0.001). Actually, early vaccination with complete(2 doses) and booster regimes(3 doses) provided lower length of protection compared to vaccinating later with incomplete(1 dose) and complete regime(2 doses), respectively. Vaccination with complete and booster regimes significantly increases the tRI(q<0.001). Conclusion: Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected. Booster doses increase the time to reinfection. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.
Subject(s)
COVID-19ABSTRACT
COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+CCR7- T{gamma}{delta} cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note up to 7 subsets were found within the CD45RA+CCR7- T{gamma}{delta} population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 mRNA vaccines.
Subject(s)
COVID-19 , LymphomaABSTRACT
SARS-CoV-2 causes a severe inflammatory syndrome called COVID-19 that primarily affects the lungs leading, in many cases, to bilateral pneumonia, severe dyspnea and in ~5% of the cases, death. The mechanisms through which this occurs are still being elucidated. A strong relationship between COVID-19 progression and autoimmune disorder pathogenesis has been identified as an exacerbated interferon immune response or an inflammatory condition mediated by an increase of pro-inflammatory cytokine production, among other. DNA methylation is known to regulate immune response processes, thus COVID-19 progression might be also conditioned by DNA methylation changes not studied in depth, yet. Thus, here an epigenome-wide DNA methylation analysis combined with DNA genotyping for 101 and 473 SARS-CoV-2 negative and positive lab tested individuals, respectively, from two different clinical centers is presented in order to evaluate the implications of the epigenetic regulation in the course of COVID-19 disease. The results reveal the existence of an epigenome regulation of functional pathways associated with the COVID-19 progression, such as innate interferon responses, hyperactivation of B and T lymphocytes, phagocytosis and innate C-type lectin DC-SIGN. These DNA methylation changes were found to be regulated by genetic loci associated with COVID-19 susceptibility and autoimmune disease. In mild COVID-19 patients hypomethylation of CpGs regulating genes within the AKT signaling pathway, and the hypermethylation of a group of CpGs related to environmental traits regulating IL-6 expression via the transcription factor CEBP, discriminate these individuals from those who develop the most critical outcomes of the disease. Thus, the analysis points out to an environmental contribution that mediated by DNA methylation changes in SARS-CoV-2 positive patients, might be playing a role in triggering the cytokine storm described in the most severe cases. In addition, important differences were found in terms of epigenetic regulation between severe and mild cases when compared with systemic autoimmune diseases.