key: cord-1000022-hktl148r
authors: Pham, Amelie; Aronoff, David M.; Thompson, Jennifer L.
title: Maternal COVID-19 disease, vaccination safety in pregnancy, and evidence of protective immunity
date: 2021-07-24
journal: J Allergy Clin Immunol
DOI: 10.1016/j.jaci.2021.07.013
sha: 1b5be5d6ad0e983c7d37c694339c9484d156fec9
doc_id: 1000022
cord_uid: hktl148r

nan

Over the past 18 months, the world has seen the largest pandemic, caused by the severe acute 25 respiratory syndrome (SARS) coronavirus 2 (CoV-2). As of June 28 th , 2021, the Center for 26

Disease Control (CDC) reported 98,948 cases of COVID-19 infection in pregnancy and 109 27 related maternal deaths in the United States alone. (1) As the pandemic continues to evolve, the 28 rapid and overwhelming increase in available evidence on the impact in pregnancy has resulted 29 in studies of varying degrees of bias and quality. In this brief review, we seek to fill some of the 30 knowledge gaps regarding maternal care considerations and answer some key questions about 31 vaccination safety in pregnancy and evidence of protective immunity ( Figure 1) . 32 33

Clinical findings: symptoms, labs, imaging 35

Maternal COVID-19 disease varies widely, but clinical course, laboratory findings, and 36 radiological patterns found in pregnancy (Table 1 ) are similar to the non-pregnant population.(2) 37

Although some patients may be asymptomatic, presence of any COVID-19 symptoms was found 38 to be associated with increased maternal morbidity and mortality.(1) 39 40 ( (ICU) admission, and lower birth weight, compared to asymptomatic mothers.(3) Pregnancy is 50 also independently associated with an increased risk for ICU admission, needing extracorporeal 51 membrane oxygenation, and maternal death among patients with symptomatic COVID-19 52 infection. Moreover, comorbidities (body mass index higher than 35 kg/m 2 , diabetes, and 53 cardiovascular disorders) and advanced maternal age also appear to have an independent risk for 54 adverse maternal outcomes. In utero fetal production of immunoglobulin (Ig) G and IgM antibodies start in the 20th week of 69 gestation, therefore the majority of neonatal IgG is of maternal origin. IgG positivity cannot 70 support or refute vertical transmission. IgM antibodies do not cross the placenta and therefore 71

IgM presence in the fetus or neonate is thought to represent fetal or neonatal production in 72 response to an infection. However, in case reports describing identification of COVID-19 IgM 73 antibodies in the neonate, infants have been asymptomatic and tested negative for SARS-CoV-2 74 viral RNA at birth. While plausible that the presence of these IgM antibodies represents 75 crossover from maternal to fetal circulation, the presence of IgM antibodies in these infants 76 could provide evidence for intrauterine vertical transmission. There are some case reports 77 demonstrating evidence of transplacental transmission, however these reports remain scare. 78

Overall, there is limited evidence of the timing for the production of IgM and IgG during 79 COVID-19 infection or the timeline for development of long-term immunity and more data are 80 needed regarding the potential and appropriate testing to determine risk of vertical transmission. 81 82

There are currently three approved vaccines for use in the United States (Table 2) J o u r n a l P r e -p r o o f Pregnant individuals with SARS-CoV-2 infection during pregnancy are at increased risk of cesarean delivery, hypertensive disorders of pregnancy, preterm birth, venous thromboembolism (VTE), intensive care unit (ICU) admission, Extracorporeal membrane oxygenation (ECMO), and maternal mortality. Treatment of pregnant infected individuals is similar to nonpregnant individuals and includes multidisciplinary team-based approach, corticosteroids, remdesivir, monoclonal antibodies and delivery timing based on obstetric interventions. Neonates exposed to SARS-CoV-2 have increased rates of prematurity, neonatal ICU admission, and low birth weight. Possible mechanisms of transmission include vertical transmission (approximately 3.2% of neonates exposed to SARS-CoV-2 in utero) or through exposure to infected respiratory droplets during the postnatal period. Vaccines against SARS-CoV-2 in pregnancy generate a higher immune response than natural infection and provide passive protective immunity through the placenta and breastmilk.

Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 136 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr. 2021

SARS-CoV-2 (COVID-138 19) infection in pregnant women: characterization of symptoms and syndromes predictive of 139 disease and severity through real-time

Disease 141 Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease

Coronavirus Infections and Neonates Born to Mothers with SARS-CoV-2: A Systematic Review

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Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

COVID-19 vaccine 152 response in pregnant and lactating women: a cohort study

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA 155 COVID-19 vaccine

COVID-19) Messenger RNA Vaccination in Pregnant Women and 158 Transplacental Passage Into Cord Blood

Maternal 160 and Neonatal Characteristics and Outcomes of COVID-19 in Pregnancy: An Overview of 161 Systematic Reviews