key: cord-1017853-f1vavr4a authors: Massalha, Manal; Yefet, Enav; Rozenberg, Orit; Soltsman, Sofia; Hasanein, Jamal; Smolkin, Tatiana; Alter, Adi; Perlitz, Yuri; Nachum, Zohar title: Vertical transmission and humoral immune response following maternal infection with SARS-CoV-2 - A prospective multicenter cohort study date: 2022-04-13 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2022.04.001 sha: 928a001009c48029f0945027e995eb660f556d24 doc_id: 1017853 cord_uid: f1vavr4a OBJECTIVE: To explore maternal humoral immune responses to SARS-CoV-2 infection and the rate of vertical transmission. METHODS: A prospective cohort study was conducted at two university-affiliated medical centers in Israel. Women positive for SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR) test during pregnancy were enrolled just prior to delivery. Levels of anti-SARS-CoV-2 spike-IgM, spike IgG and nucleocapsid IgG were tested in maternal and cord blood at delivery, and neonatal nasopharyngeal swabs were subjected to PCR testing. The primary endpoint was the rate of vertical transmission, defined as either positive neonatal IgM or positive neonatal PCR. RESULTS: Among 72 women, 36 (50%), 39 (54%) and 30 (42%) were positive for anti-spike-IgM, anti-spike-IgG and anti-nucleocapsid-IgG, respectively. Among 36 neonates in which nasopharyngeal swabs were taken, one neonate (3%, 95% confidence interval 0.1%-15%) had a positive PCR result. IgM was not detected in cord blood. Seven neonates had positive IgG antibodies while their mothers were seronegative for the same IgG. Anti-nucleocapsid-IgG and anti-spike-IgG were detected in 25/30 (83%) and in 33/39 (85%) of neonates of seropositive mothers, respectively. According to the serology test results during delivery with respect to the time of SARS-CoV-2 infection, the highest rate of positive maternal serology tests was 8-12 weeks post-infection (89% anti-spike IgG, 78% anti-spike IgM and 67% anti-nucleocapsid IgG). Thereafter, the rate of positive serology tests declined gradually; at 20 weeks post-infection, only anti-spike IgG was detected in 33-50%. CONCLUSIONS: The rate of vertical transmission of SARS-CoV-2 was at least 3% (95% confidence interval 0.1%-15%). Vaccination should be considered no later than 3 months post-infection in pregnant women due to a decline in antibody levels. rate of vertical transmission. Methods: A prospective cohort study was conducted at two university-affiliated medical 28 centers in Israel. Women positive for SARS-CoV-2 reverse-transcription-polymerase-chain-29 reaction (RT-PCR) test during pregnancy were enrolled just prior to delivery. Levels of anti-30 SARS-CoV-2 spike-IgM, spike IgG and nucleocapsid IgG were tested in maternal and cord 31 blood at delivery, and neonatal nasopharyngeal swabs were subjected to PCR testing. The The effect of pregnancy on humoral response to SARS-CoV-2 infection as well as the rate of 51 vertical transmission are not fully understood. At the beginning of the current COVID-19 52 pandemic, evidence pointed to a lack of vertical transmission, as determined by amniocentesis, 53 umbilical cord blood, placenta, neonatal secretion and breast milk sampling [1] [2] [3] [4] [5] [6] . However, 54 recent data, mostly from case reports and case series, demonstrated the presence of SARS- Boards (60-20-EMC and 90-20-POR). Informed consent was obtained from all individuals who 68 participated in the study. During the study period vaccination was not available in Israel. The study cohort consisted of pregnant women≄18 years old who had a positive 70 nasopharyngeal swab for SARS-CoV-2, as determined by RT-PCR, during pregnancy. 94 was estimated to be 7% when defined by RT-PCR [6] . Assuming that using serology tests 97 increases the rate to 10% versus 0% in non-infected population, 71 women were required (80% 98 power, 5% one-sided alpha). Categorical variables were analyzed using the chi-squared test or Fisher's exact test. The Statistical analyses were carried out with SAS version 9.4 (SAS Institute, Cary, NC, USA). Significance was set at a p value of <0.05. Data were analyzed by the authors E.Y and Z.N. Seventy nine women were offered to participate in the study. All of them agreed to participate. Among them, 72 had available serology test results. Seven women did not have serology 111 information due to technical reasons. Thirty six neonates did not undergo nasopharyngeal 112 swabbing for SARS-CoV-2 PCR due to parental refusal. One woman did not have enough 113 serum to determine anti-spike IgM levels. Patient characteristics are presented in Table 1 . SARS-CoV-2 antibody profiles of women who 115 had COVID-19 during pregnancy and of their neonates, are presented in Table 2 . Among the anti-spike-IgM responses (Figure 1,B) . The rate of women with positive IgG serology was higher if COVID-19 was symptomatic Clinical characteristics and intrauterine 203 vertical transmission potential of COVID-19 infection in nine pregnant women: a 204 retrospective review of medical records Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: 208 two weeks of confirmed presentations to an affiliated pair of New York City hospitals COVID-19) Maternal and Neonatal Outcomes of 213 Pregnant Women With Coronavirus Disease Chinese expert consensus on the perinatal 216 and neonatal management for the prevention and control of the 2019 novel coronavirus 217 infection Coronavirus Disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: Should 220 We Worry? Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection Detection of 225 severe acute respiratory syndrome coronavirus 2 in placental and fetal membrane samples Visualization 228 of severe acute respiratory syndrome coronavirus 2 invading the human placenta using 229 electron microscopy Severe COVID-19 232 during Pregnancy and Possible Vertical Transmission Possible Vertical Transmission of SARS-235 CoV-2 From an Infected Mother to Her Newborn Preterm 238 delivery, maternal death, and vertical transmission in a pregnant woman with COVID-19 239 infection Vaginal delivery in 241 SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis Antibodies in Infants Born to Mothers 244 With COVID-19 Pneumonia Infection during Pregnancy: Risk of 247 Vertical Transmission, Fetal, and Neonatal Outcomes Vertical 250 transmission of coronavirus disease 2019: a systematic review and meta-analysis SARS-CoV-2 253 positivity in rectal swabs: implication for possible transmission SARS-CoV-2 antibody 256 dynamics and B-cell memory response over time in COVID-19 convalescent subjects Coronavirus disease 2019 259 (COVID-19) pandemic and pregnancy An immune 262 clock of human pregnancy Fetal sex-based differences 264 in maternal hormones, angiogenic factors, and immune mediators during pregnancy and the 265 postpartum period 268 Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19