High rates of SARS-CoV-2 infection in pregnant Ugandan women and association with stunting in infancy

Background SARS-CoV-2 has been well studied in resource-rich areas but many questions remain about effects of infection in African populations, particularly in vulnerable groups such as pregnant women. Methods We describe SARS-CoV-2 immunoglobulin (Ig) G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. Results From December 2020 to February 2022, among 400 unvaccinated pregnant women, serologic assessments revealed that 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected either prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time. No participants experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infection (- 1.54 versus −0.37 and −0.51, p=0.009). Conclusion Pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with shorter stature in early infancy. Funding This work was supported by: Stanford MCHRI/Stephen Bechtel Endowed Fellowship in Pediatric Translational Medicine (KJ), Swiss National Science Foundation PRIMA grant PR00P3_208580 (KR), the Bill and Melinda Gates Foundation, and NIAID (T32-AI052073, U01- AI141308, U01-AI155325). ### Competing Interest Statement J.N.W. and G.B.S. are employees of Meso Scale Diagnostics (MSD). All other authors have declared that no conflict of interest exists. ### Funding Statement This work was supported by: Stanford MCHRI/Stephen Bechtel Endowed Fellowship in Pediatric Translational Medicine (KJ), Swiss National Science Foundation PRIMA grant PR00P3_208580 (KR), the Bill and Melinda Gates Foundation, and NIAID (T32-AI052073, U01-AI141308, U01-AI155325). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Recruitment of patients, documentation of written informed consent prior to participation, collection of blood specimens, and experimental measurements were carried out with Institutional Review Board approval from the Stanford University Panel on Medical Human Subjects(Stanford, CA, USA), the UCSF Human Research Protection Program Institutional Review Board (San Francisco, CA, USA) and the Makerere University College of Health Sciences School of Biomedical sciences Research Ethics Committee (Kampala, Uganda). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Underlying data and supporting analytic code for the article can be accessed upon request.