outcomes (as per outcomes 1–4 above) as compared to pregnant women who are not infected with SARS-CoV-2; 2. to estimate the risk of MTCT of SARS-CoV-2 virus during pregnancy, intrapartum, postpartum (including during breastfeeding) among mother–neonate pairs with confirmed SARS-CoV-2 infection in pregnancy; 3. to describe viral presence and persistence in amniotic fluid, placenta, cord blood, fetus, neonate as well as in breast milk and other bodily fluids (urine, faeces, vaginal fluids); 4. to characterize the clinical course and disease spectrum of COVID-19 during pregnancy. SARS-CoV-2 and pregnancy prospective cohort study Generic protocol: Last updated 2 December 2020, version 212 Secondary objectives include, but are not limited, to: 1. estimate the cumulative incidence of asymptomatic, subclinical and clinically apparent SARS-CoV-2 infection during pregnancy, as assessed by seroconversion or a positive reverse transcriptase polymerase chain reaction (RT-PCR) test during and following pregnancy; 2. measure the frequency of detectable RNA for SARS-CoV-2 by RT-PCR and IgG/IgM antibodies in neonates born to women infected with SARS-CoV-2 during pregnancy; 3. characterize the signs, symptoms and disease course of neonates who have SARS-CoV-2 infection following childbirth from a pregnant woman infected with SARS-CoV-2. Optional secondary objective: To determine if the disease severity and disease characteristics of COVID-19 are different in pregnant women compared with non-pregnant women of reproductive age. Please see Appendix D for details regarding this optional secondary objective. COMMENT: Additional secondary objectives can be included in the protocol and will be informed by the outbreak characteristics and by the local context. 4 Required elements of protocol This generic protocol is designed to be adapted to the local context of the implementing research institutions and sites. The components of this study that should be applied across all study sites include the inclusion/exclusion criteria of study participants and assignment of participants to study groups (see Fig. 1). In addition, it is expected that institutions adopting the generic protocol will utilize the generic case report forms (CRFs) provided in the appendix. These CRFs represent the suggested core of variables that sites should collect data on; however, the CRF is intended to be flexible with online data entry platforms including skip logic to allow sites to omit variables that cannot be collected. In addition, sites are welcome to add additional sections and/or variables to the CRF, if relevant for their context. 5 Methods 5.1 Study design 5.1.1 Objectives 1, 3, 4 and secondary objectives This is a prospective longitudinal open cohort study of pregnant women exposed to SARS-CoV-2 or not exposed that will be recruited consecutively over time until the desired study sample size is achieved. It will compare clinical, pregnancy, perinatal and neonatal outcomes for women with confirmed SARS-CoV-2 infection during pregnancy and the postpartum period of 6 weeks following the end of pregnancy (exposed) with pregnant women not diagnosed with SARS-CoV-2 infection during this period (unexposed). Where possible, assignment of participants into exposed, unexposed and unknown groups will be based on the results of RT-PCR testing. In some settings, analysis of SARS-CoV-2 RT-PCR may not be available due to SARS-CoV-2 and pregnancy prospective cohort study Generic protocol: Last updated 2 December 2020, version 213 limited laboratory capacity. In these situations, the study design may be adapted to use serology testing for IgG/IgM antibodies for group assignment (as described below and in Fig. 2). Pregnant women will be enrolled into the exposed group of the cohort if they have tested positive for acute SARS-CoV-2 infection by RT-PCR before or until 14 days after pregnancy termination. Diagnostic testing should be available for review to confirm positive RT-PCR testing. Pregnant women will be enrolled into the (SARS-CoV-2 negative) unexposed group after negative RT-PCR and negative antibody testing. Pregnant women with negative RT-PCR (SARS-CoV-2 negative) in settings that do not have access to antibody test will be enrolled in the unknown group. Serology samples may be drawn from this group and saved for future analysis, in case antibody tests become available at a later date. To conserve the limited number of diagnostic tests for SARS-CoV-2 RNA by RT-PCR, the entry point of the cohort is SARS-CoV-2 testing or screening of suspected cases or asymptomatic pregnant women, irrespective of hospitalization due to COVID-19. Crossover between groups will be allowed. Women enrolled into the SARS-CoV-2 negative (unexposed) group who seroconvert during the pregnancy will crossover into the SARS-CoV-2 positive (exposed) group. Infants born to mothers enrolled in the cohort, as well as the mothers themselves, will be followed for 6 weeks after childbirth. Women who are SARS-CoV-2 negative with unknown serology (unknown) may crossover into the SARS-CoV-2 negative and serology negative (unexposed) group if/when antibody testing becomes available and they test antibody negative (see Fig. 1). SARS-CoV-2 and pregnancy prospective cohort study Generic protocol: Last updated 2 December