The effect of SARS-CoV-2 on the susceptibility of respiratory outcomes in a Puerto Rican Birth Cohort

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PROJECT SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The lack of diagnostic tests and current public health policies limit our knowledge of the true prevalence of SARS- CoV-2. Infection with SARS-CoV-2 results in production of anti-viral antibodies in infected hosts, yet it is currently unknown whether these antibody responses are protective against subsequent infection. Survivors of the 2003 SARS coronavirus outbreak had reduced lung function and quality of life, and more frequent viral respiratory illnesses. The latter are associated with increased risk for childhood wheeze and asthma, the most common chronic and disparate disease among children. Data also indicate that there are significant racial/ethnic disparities in COVID-19 outcomes. Disparities in risk of viral exposure, susceptibility to severe disease, and access to health care may interact to exacerbate existing health inequalities. Pregnancy provides a natural mechanism by which to examine the protective potential of passive immunity. Maternal IgG is actively transported across the placenta and in the absence of postnatal exposure wane to undetectable levels in the neonate over the first year of life. Furthermore, IgA is passed from mother to child through breastmilk. Our multidisciplinary team will study a unique cohort of Puerto Rican mothers and their infants prospectively following the infants through their first five years of life collecting maternal breastmilk, maternal and neonatal cord blood, and neonatal/infant nasal epithelium swabs at birth, during respiratory illness, and at yearly clinical evaluations. We will determine prenatal exposure to SARS-CoV-2 as measured from maternal and infant cord blood at time of birth and investigate the effect this virus has on the susceptibility of respiratory disease in children. We will screen all pre/postpartum mothers with a PCR assay and qualitative immunoassay to detect SARS-CoV-2 infection. Among all seropositive mothers, we will collect repeated breast milk samples at 5 and 14 days and serial newborn blood spot samples at birth, 1, 3, 6 months, and yearly for 5 years. We will measure IgA, IgG, and IgM in maternal breastmilk and blood samples, and IgG in infant serum. We will examine (Aim 1) the passive transfer of SARS-CoV-2 immunity from seropositive mothers to their neonates, (Aim 2) whether early life SARS- CoV-2 infection severity and other clinical sequelae is modified by altered childhood immunophenotypes and host genetics, and (Aim 3) how socio-environmental factors affect maternal and infant exposure to COVID-19 and further affect the development of childhood asthma. We hypothesize that pregnant women infected with SARS-CoV-2 produce neutralizing antibodies, which protect their newborns from COVID-19 disease. In contrast, infants who contract SARS-CoV-2 after birth are at increased risk for later respiratory disease including asthma and other clinical sequelae. We further postulate that these associations are modified by host genetic and socio- environmental factors. To our knowledge, there are no other groups within or outside the U.S. with the population needed and track record to perform these analyses.