Infections with SARS-CoV2 cause the coronavirus disease 2019 (COVID-19), with different clinical manifestations. Most individuals mount an IgG and IgA serum response following SARS-CoV-2 infection. Neutralizing antibodies are key in protective immunity because they block viral entry by targeting the S protein receptor¿binding domain (RBD. Patients suffering from secondary immunodeficiencies (SID) patients have enhanced morbidity and mortality following SARS-CoV-2 infection than are more vulnerable than immunocompetent (IC), but it is not clear whether they may produce more inflammatory cytokines driving an improper immune response and/or an impaired IgG/IgA against SARS-CoV-2.
The general aim of this project is to study the humoral immune responses in adult IC individuals and in adult SID patients. To that end, we will measure the levels and kinetics of antibodies and serum cytokines produced in the two groups and compare them; their relationship with demographic data, the symptoms of SARSCoV 2-infection and clinical severity of COVID-19 in IC and SID will be analyzed. We have already collected more than one hundred sera in which anti-SARS-CoV-2 IgG were measured for diagnostic or screening purpose healthcare workers pre and post-vaccination, from hospitalized patients and from SID patients attending hematooncology clinics, Policlinico Umberto I. In this study we will measure IgA by commercial EIA kit and neutralizing antibodies specific to the S protein of SARS-CoV-2 by a laboratory-adapted pseudovirus test. Longitudinal samples will be obtained from IC and SID, tracking immunity over longer periods after infection or vaccination, to test durability and levels of Ig protective titers. A Secondary Outcome may be to observe the incidence rate of SARS-CoV-2 (re)infection after a previous infection or vaccination.
This research will give further understanding of the immunoregulatory events in disease progression and the immune response to SARS-CoV-2 infection.
Despite numerous studies on the subject, a deeper understanding of the immune response after asymptomatic and symptomatic SARS-CoV-2 infections is needed.
By comparing the humoral response of previously healthy individuals to a group of well-characterized patients with SID due to underlying pathologies or medical treatments, we will contribute to the understanding of what is an efficient response to SARS-CoV-2 infection. In the SID group, reinfections or infections in vaccinated individuals will be prospectively monitored for 18 months, to appreciate whether a level of any Ab type (IgG, IgA and neutralizing Ab) could correlate with protection.
With our project, we will try to address many open questions. How long serology persists after SARS CoV-2 infection, either mild or severe? Are antibody responses or circulating cytokine levels associated to a protective immunity against SARS CoV-2 reinfection? Do SARS CoV-2 specific immunity play a role in COVID-19 clinical manifestation and in Long-COVID in SID?
The findings of this research will further our understanding of the immunoregulatory events in disease progression and the immune response to SARS-CoV-2 infection.
Data obtained from our study may provide critical information for decision-making in ongoing clinical practice. We will be able to define SID patient groups who: a) developed a protective immune response post Covid-19 or vaccination and are therefore most likely save to return to normal social life and work and b) developed a very low/insufficient humoral immune response who are at risk of severe Covid-19 and may require protection by anti-SARS-CoV- specific monoclonal antibodies.