2020, version 214 Figure 1. Study overview, setting with RT-PCR testing available Outcomes of interest: • Pregnancy outcomes • Fetal outcomes • Perinatal outcomes • Neonatal outcomes (6 weeks postpartum) • COVID-19 clinical spectrum • Disease severity • Viral persistence RT-PCR test IgG/IgM test IgG/IgM unknown Enrolment in Unknown group* IgG/IgM negative Enrolment in Unexposed group RT-PCR positive Enrolment in Exposed group No IgG/IgM test available Save serology samples for future analysis RT-PCR negative IgG/IgM positive Exclusion RT-PCR negative PCR or seroconversion during pregnancy * Crossover to Exposed group if positive RT-PCR Presentation of pregnant woman at COVID-19 testing centre, health facility or antenatal care Monthly follow-up during pregnancy In settings that have limited laboratory capacity for analysing RT-PCR specimens, assignment of pregnant women to study groups may be done using IgG/IgM serology testing (see Fig. 2). With this design, women with a positive IgG/IgM serology test would be enrolled in the exposed group. Women with a negative IgG/IgM serology test would be enrolled in the unexposed group. Crossover from the unexposed to the exposed group may occur when a woman seroconverts during the course of the pregnancy, after her initial enrolment in the study. SARS-CoV-2 and pregnancy prospective cohort study Generic protocol: Last updated 2 December 2020, version 15 Figure 2. Study overview, setting with no capacity for RT-PCR testing Outcomes of interest: • Pregnancy outcomes • Fetal outcomes • Perinatal outcomes • Neonatal outcomes (6 weeks postpartum) • COVID-19 clinical spectrum • Disease severity • Viral persistence No IgG/IgM test available Save serology samples for future analysis IgG/IgM test IgG/IgM negative Enrolment in Unexposed group IgG/IgM unknown Enrolment in Unknown group* IgG/IgM positive Enrolment in Exposed group Seroconversion during pregnancy * Crossover to Exposed group if positive IgG/IgM Presentation of pregnant woman at COVID-19 testing centre, health facility or antenatal care Monthly follow-up during pregnancy COMMENT: The WHO Emergency Use Listing2 dated 2 October 2020 and interim guidance on diagnostic testing for SARS-CoV-2 published 11 September 2020 (19) encourage the use of antigen-based rapid diagnostic tests (RDTs) especially in contexts with limited laboratory capacity. Investigators can opt to assign study participants into groups based on RDT results. While evidence of the performance of these tests is still emerging, kindly refer to the WHO guidance on considerations for the use of RDTs. 3 Note that point-of-care immunodiagnostic tests are only recommended for research purposes and not as a basis for clinical decisionmaking (20). 2 WHO. WHO Emergency Use Listing for in vitro diagnostics (IVDs) detecting SARS-CoV-2 (www.who.int/diagnostics_laboratory/201002_eul_sars_cov2_product_list.pdf). 3 WHO. Antigen-detection in the diagnosis of SARS-CoV-2 infection using rapid immunoassays (334253). SARS-CoV-2 and pregnancy prospective cohort study Generic protocol: Last updated 2 December 2020, version 16 5.1.2 Specific study design for Objective 2 Postpartum and breastfeeding risk of transmission will be assessed in comparison to SARS-CoV-2 noninfected/unexposed mother–neonate pairs. Optional secondary objective Additionally, this study protocol provides the option of a nested case-control design, to be considered if the study sites have limited ability to perform antibody testing for all women (unknown exposure group). Please see Appendix D regarding this optional design. Study setting/s This study is designed to be conducted in areas with an ongoing COVID-19 outbreak. COVID-19 outbreak areas are defined as areas where disease surveillance detects community transmission of SARS-CoV-2 virus based on WHO epidemiologic studies or local surveillance data. The implementation protocol should clearly define the catchment area of included health facilities and describe the study base of the study sample. 5.2 Study participants and sampling 5.2.1 Study population - Inclusion criteria: pregnant women (up to 2 days postpartum at time of enrolment) (Pregnant women with co-morbidities are eligible) - Exclusion criteria: non-pregnant women. Evidence of immunity to SARS-CoV-2 prior to pregnancy start (+ IgG/IgM SARS-CoV-2 serology and no evidence of ongoing infection as in RT-PCR positivity at the time of enrolment). NOTE: serology may need adaptation in relation to resources and availability. In some sites, only clinical history, negative PCR and the end point serology may be used. 5.2.2 Exposure status 1. Exposed status will consist of pregnant women who have tested positive by RT-PCR for SARS-CoV-2 during their current pregnancy or immediate postpartum period. Alternatively, in settings where RTPCR is not available and/or RT-PCR samples cannot be analysed, women may be enrolled in the exposed group if they have detectable IgG/IgM antibodies during their current pregnancy or immediate postpartum period and no RT-PCR result. Participants enrolled as unexposed will crossover to the exposed group if there is evidence of seroconversion or positive RT-PCR for SARSCoV-2 after study enrolment. Women who have