Characterization of COVID-19 and post-acute sequelae of SARS-CoV-2 infection cohort study: the role of CD169 as a biomarker of systemic dysfunction and its alteration respect to SARS-CoV-2 pandemic waves

Background: The COVID-19 pandemic was characterised by rapid spread and mutation of the SARS-CoV-2 virus, resulting in the emergence of different variants of concern (VOCs) that defined distinct pandemic waves. In this critical scenario, the persistent of multisystemic dysfunction after resolution of SARS-CoV-2 infection were associated with the “post-acute sequelae of SARS-CoV-2 infection condition” (PASC), presenting new significant challenges worldwide in the public health. Aim: Considering the need to implement the characterization of the disease, the aim of this study was to analyse the potential impact of different pandemic waves in COV patients and PASC individuals evaluating the clinical features during the acute phase of SARS-CoV-2 infection. Moreover, the expression of CD169 and HLA-DR on monocytes from COVID-19 patients and PASC individuals were analysed to better elucidate their involvement in immunological dysfunction, taking in to account the possible impact of the pandemic waves. Material and methods: 133 COV patients and 132 PASC individuals were characterised according with severity, pneumonia involvement, respiratory outcome and treatments during acute phase of SARS-CoV-2 infection, and comorbidity aspects. PASC individuals based on the distribution of symptoms during post-acute phase were also evaluated. Flow cytometry was used for the evaluation of the median fluorescence intensity ratio of CD169 between monocytes and lymphocytes (CD169 RMFI) in blood samples from COV, PASC and 59 healthy donors (HD). Leukocytes subpopulations were characterized for CD169+, HLADR+ and CD169+ HLA-DR+. The different markers analysed have been associated with COVID-19 severity, vaccinations, clinical and biochemical parameters in COV and PASC, also considering COVID-19 pandemic waves. Results: The study showed that the wave III was the most critical considering COV patients during pandemic waves. Moreover, mild and severe condition of COV were immunologically similar, and the vaccine modulated immune response in COV. Differently, the occurrence of PASC symptoms was no associated with the administration and time of vaccination, and COVID-19 severity. Furthermore, the results confirmed that CD169 RMFI is a good marker of viral infection. COVID-19 patients and PASC individuals showed high percentage of CD169+ monocytes, but low percentage of HLA-DR+ monocytes. Moreover, examining CD169 and HLA-DR expression on monocytes in COVID-19 and PASC during different pandemic waves, the study has revealed correlations with inflammatory markers and coagulation parameters. Conclusions: The study of different pandemic waves allowed to better characterize the clinical features of COV 5 and PASC during the acute phase of SARS-CoV-2 infection. PASC sequalae could be associated with the genetic and immunological characteristics of PASC individuals, involved in the response against SARS-CoV-2. The persistence of specific myeloid subpopulations suggests a role of CD169+ monocytes and HLA-DR in COVID-19 disease and chronic post-infection inflammation, opening new opportunities to evaluate the impact of specific pandemic waves on the immune response impairment and systemic alterations with the perspective to provide new tools to monitoring new variants and diseases associated to emerging respiratory viruses.