Persistent SARS-CoV-2 Infection in Children With Cancer and Impaired Immune Responsiveness

Although the adaptive immune response plays an important role in improving clinical outcomes of patients infected with SARS2, variability in clinical disease and outcome in patients with SARS2 infection has not been explained by the variation in qualitative and quantitative antiviral immune responses. It has been observed that immunocompromised children shed the virus from the upper respiratory tract for prolonged periods of time, even after the resolution of clinical symptoms. Thus deficits in adaptive immune responses might lead to ineffective control of virus replication and prolonged virus shedding. The proposed studies will define the relationship between adaptive immunity and virus replication/shedding, including the contribution of viral variants that could arise during poorly controlled virus replication in children with ineffective immune responses. The specific aims of the proposed study are: (a) To measure (quantify and qualify) the adaptive immune responses (humoral and cell-mediated immune responses) after infection with SARS-CoV-2 in a cohort of hospitalized children with cancer and impaired immune response. (b) To define the long-term kinetics of the antibody response, cell-mediated immune responses following infection with SARS-CoV-2 in a cohort of hospitalized children with cancer and impaired immune response, and to estimate the duration of protective immunity.(c) to statistically assess whether impaired humoral immunity is associated with prolonged viral replication and shedding (persistence) following infection with SARS-CoV-2 in a cohort of children with cancer and impaired immune response, (d) To genetically trace SARS-CoV-2 mutations, and statistically assess the association between persistent SARS-CoV-2 infection and the frequency of viral mutations and the emergence of viral variants in a cohort of children with cancer and impaired immune response, after their infection with SARS-CoV-2 This will be a prospective, observational cohort study design. The study population will include pediatric and adolescent patients undergoing cancer chemotherapy with a confirmed SARS-CoV-2 infection (PCR Positive). Eligible subjects will be followed prospectively for three months from the time they tested positive for SARS-CoV-2 by PCR. SARS-CoV-2 RNA, antibody, and cell-mediated immune responses will be assessed at specified time points and compared between the children with persistent SARS-CoV-2 infection, and those who cleared SARS-CoV-2 virus. Sequence viral variants in the persistent SARS-COV-2 infected group Assess the association between the emergence of viral variants and mutations and strain virulence and clinical outcome