Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2: phenotypic and functional analysis of monocytes, NK and T cells in the blood of subjects affected by COVID 19 (Preprint)

BACKGROUND The novel coronavirus has a high mortality rate (over 1% for patients older than 50). This could be only partially ascribed to other comorbidities. Possible explanation could be something which assures the ability to prompt response to SARS-CoV-2 in younger people independently from the novelty of the virus itself. Something stimulated the immune system and it scattered immunity against more antigens. The only external stimulation, which healthy people receive, is vaccination (i.e. diphtheria, tetanus, and pertussis (DTP) vaccine). One hypothesis is that vaccination develops the specific immunity but generates a sprouting immunity against antigens in transit. The underlying immunological phenomena are "bystander effect" and "trained immunity". The developed immunity gives protection for years until the natural fade out. After the fifth decade a viral infection will find immune system almost incompetent and the novel coronavirus bursts into the body, developing an ARDS. OBJECTIVE The first study's aim is to demonstrate that blood monocytes and NK cells show an overpowering hyperactivity, while CD4+ and CD8+ T cells experience an impediment to their defensive functions, in patients with severe infection to SARS-CoV-2. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune pattern, to identify protective factors. Subsequently, we were also interested in characterizing the phenotype and state of degree of activation within peripheral blood mononuclear cells (PBMC), of monocytes, NK cells, CD4+ and CD8+ T cells in healthy subjects vaccinated with Pfizer. METHODS Data will be collected using 3 approaches: An experimental analysis to study the innate immune response and to identify the genetic profiles; An epidemiological analysis to identify the patients' vaccination history; A clinical analysis to detect the immunological profile. RESULTS The protocol was approved by the Ethics Committee on 16 April 2020 and the study started on 27 April 2020. As of February 2021 enrollment was completed. Immunological analysis is going on and we expect to complete this analysis by December 2021. CONCLUSIONS We suppose to recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factors serum level and immune cells activity. Anamnestic data such as preceding vaccinations and comorbidities, biochemical data findings as lymphocyte immunophenotyping and pre-existing persistent cytomegalovirus infection allow depicting the risk profile of severe COVID-19. The proof of a role of these immunological phenomena on the development of COVID-19 are bases for implementation of therapeutic immunomodulatory treatments. CLINICALTRIAL The protocol is available on the ClinicalTrials.gov website, its identifier is NCT04375176 (https://clinicaltrials.gov/ct2/show/NCT04375176?term=NCT04375176&draw=2&rank=1). INTERNATIONAL REGISTERED REPORT DERR1-10.2196/29892.