Influenza & COVID Obstetric and Perinatal Epidemiology Study in India

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS- CoV-2) was first reported in Wuhan, Hubei Province of China in December 2019 and by early 2021, there have been more than 100 million cases of COVID-19 globally. The consequences of COVID-19 in pregnant women in high/upper middle-income countries are under intensive investigation. There are few parallel studies in low/lower middle- income countries (LMIC) and data on COVID-19 infection in high-income countries may not be generalizable to LMIC. Given the large number of the world's births that occur in LMIC, there is an urgent need to understand the risk of COVID-19 (and other respiratory viruses (ORV), particularly influenza) to pregnant women and newborns. Our group recently led the Indian site of the Centers for Disease Control and Prevention study on the impact of laboratory confirmed influenza in pregnant women in 3 LMICs, finding that influenza was associated with late pregnancy loss and reduced mean birthweight. Leveraging this recently completed study and 10 years of experience of studying ~10,000 pregnant women a year in Central India, we now propose the "Influenza & COVID Obstetric and Perinatal Epidemiology (ICOPE) Study in India." ICOPE will enrol 10,000 pregnant women presenting to a large obstetric hospital in Nagpur, India for antenatal care. Important features of our study include: (i) documented ability to recruit women in the first trimester of pregnancy (ultrasound confirmed); (ii) twice weekly follow-up for COVID-19/ORV/Influenza symptoms, combined with laboratory testing for symptomatic and asymptomatic infection (reverse transcription-polymerase chain reaction testing of nasopharyngeal swabs and frequent collection of dried blood spots for COVID IgG and IgM) during pregnancy through day 7 post-partum. Neonates with critical illness will be assessed for COVID-19 and influenza and dried blood spots will be obtained for COVID antibodies on day 7 of life. Pregnant women admitted with COVID-19 will have specimens obtained to evaluate trajectories of inflammatory cytokines. We will biobank dried blood spots for future studies. Our specific aims are to: (1) determine the prevalence, incidence and maximal severity of symptomatic or asymptomatic COVID-19 in pregnant women to day 7 postpartum and whether influenza/ORV infection or vaccination modifies and pre-term birth mediates this risk; (2) determine the effect of maternal COVID-19 infection on the fetus and/or neonate to day 7 of life; and whether influenza/ORV or vaccination modifies and pre-term birth mediates this risk; (3) characterize patterns and trajectories of host response/inflammatory biomarkers as potential mediators of COVID-19±influenza infection on progression to severe illness in pregnant women/mothers admitted with COVID-19. Modifiers include vaccination. ICOPE is well positioned to provide information on the impact of COVID-19 and ORV, across all trimesters, over time in a LMIC setting.