key: cord-1022456-srqux2hj authors: Newman, Connie; Henderson, Cassandra; Laraque-Arena, Danielle title: COVID-19 and Pregnancy: A public health, evidence-based approach date: 2021-12-16 journal: J Natl Med Assoc DOI: 10.1016/j.jnma.2021.12.004 sha: 77874ea05727345de18df780282c76b4e9035f9a doc_id: 1022456 cord_uid: srqux2hj nan Pregnancy can be affected by medical comorbidities. It is known that pregnant individuals are susceptible to severe illness due to some viral infections, as evident in the H1N1 pandemic, with potential explanations such as the physiological changes of reduced lung volume from displacement by the uterus, and a dysregulated inflammatory cascade, characterized by -silencing‖ of Th1 pro-inflammatory response and strengthening of Th2 response to fend against miscarriage. 1 As the world continues to fight against the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, the resurgence in hospitalizations and deaths worldwide, makes it imperative to place in context the risks this virus poses during and after pregnancy. More than 3,500 reports are in the literature, but what is missing are high quality longitudinal data on COVID-19 and pregnancyrelated outcomes, adverse effects to the fetus, and the health of the infant to inform policy and practice. This commentary aims to identify the gaps in research that would inform and enable timely, prospective collection and dissemination of data to drive shared decision making with pregnant individuals in the era of COVID-19. A search in PubMed of COVID-19 and pregnancy as of September 21, 2021 revealed 3579 articles. Early information from Wuhan, China, at the beginning of this pandemic on the severity of disease during pregnancy suggested a mild course in 109 of 118 women, with severe disease in 9 (8%) and mechanical ventilation required by 1 woman. 2 Subsequently, many reports, and some meta-analyses or systematic reviews of the data from these reports, have described symptoms and adverse outcomes in pregnancies affected by COVID-19. Many of these reports are retrospective, do not compare pregnant to non-pregnant individuals, and lack data on maternal and neonatal outcomes. Pre-term births have been frequent but reported to be similar to the rate in the general pregnant population. Additionally, it is still not known whether COVID-19 during pregnancy harms the fetus or newborn, and evidence for vertical (mother to child) transmission of SARS-CoV-2 is sparse. However, as noted by the authors, the missing information on pregnancy status in 64.5% of 1,300,938 women of reproductive age with positive tests for the SARS-CoV-2 virus, is a limitation of this study, as are missing data on race, comorbidities and outcomes. In addition, due to incomplete information, the question of whether hospitalization in the sample studied was related to COVID-19 infection or pregnancy-related conditions, could not be answered. In another report, data from pregnant women in 13 states collected and analyzed by the U.S. COVID-19 Associated Hospital Surveillance Network (COVID-NET) show that in 598 pregnant women with COVID-19 who were hospitalized, those who were symptomatic, compared to asymptomatic, were less likely to have live births (30% vs 70%) and more likely to be admitted to the intensive care unit, require mechanical ventilation and undergo treatment with steroids and vasopressors. 4 Limitations of the COVID-NET report include the use of a convenience sample of 29% of hospitalized women-those who had been discharged and had a chart review-and the missing data on birth outcomes from pregnancies completed after hospital discharge. The amount of missing data underscores the need for improving surveillance and studies of COVID-19 in pregnancy. In both the CDC and COVID NET studies, Hispanic and non-Hispanic Black pregnant women appeared to be disproportionately affected by SARS-CoV-2 infection, but due to incomplete information on race and ethnicity, a definitive conclusion cannot be reached. Based upon the information we have it is more than reasonable to limit exposure to COVID-19 by the rigorous use of appropriate social isolation and PPE for all pregnant individuals, but priority should also be placed on providing information through targeted public messaging that allows them to make informed choices. It should not be assumed that the public is not sophisticated enough to absorb complex health data -the effort should be to continuously engage and inform so that families are better equipped to understand test results and make tough decisions. For example, SARS COV1D-19 test inaccuracies, false negatives and positive rates as demonstrated in Table 1 (Table 1) . As a result, these molecular tests have become the primary means and as determined by the CDC, the -gold‖ standard for clinical diagnosis or identification of acute infections caused by SARS-CoV-2‖. 6 Public awareness of current vaccine status adjoined by clear unambiguous messages are also needed. Clarity does not negate complexity and needs to be explicit in addressing the information regarding pregnancy. As of September 26, 2021, three vaccines are approved, or authorized for emergency use, in the United States (Table 2 ) . 12-15 However, the absence of data on immunization during pregnancy makes recommendations difficult and dependent upon the COVID-19 vaccine to women during pregnancy and while breastfeeding, ages ≥ 16 and ≥18, respectively, and providing them with available safety and efficacy data, noting the lack of clinical trial data during pregnancy. ACOG also recommends vaccination while trying to conceive, and enrolling individuals who become pregnant within 30 days of vaccination in the CDC V-SAFE program, which uses a smart phone app to track health after vaccination. 16 The CDC explains on their website that mRNA vaccines are unlikely to cause a risk during pregnancy and cannot either transmit COVID 19 or alter genetic material. In a report published in June 2021, analysis of data from surveillance systems of pregnant individuals and the v-safe pregnancy registry showed no safety signals, but the investigators recommended continued data collection to assess maternal, pregnancy, neonatal and childhood outcomes. 17 In a communication on the CDC website, dated August 11, 2021, the CDC encouraged vaccination of all pregnant people, people planning a pregnancy or breastfeeding, because they are reported to be at high risk for developing severe COVID-19 related illness. 18 including those in underserved subgroups, could be developed prospectively to protect both the birthing person and the child, and public health messaging could accurately report timely information so strategies that might mitigate and prevent the worst outcomes. to decrease influenza associated pneumonia and use of intensive care resources. 20 For both of these viral respiratory diseases, influenza and COVID-19, the need to prioritize vulnerable populations is clear. Legend: Table 1 summarizes the sensitivity, specificity, predictive value positive (PPV) and predictive value negatives (PPN) for the 3 classes of tests: molecular (RT-PCR) testing; antigen testing; and antibody COVID-19 testing. PPV varies with disease prevalence when interpreting results from diagnostic tests. PPV is the proportion of positive test results that are true positives. As disease prevalence decreases, the proportion of test results that are false positives increases. Table 2 shows important information for each vaccine available in the United States, including status of FDA approval, lower limit for age, effectiveness, and demographics of the efficacy analysis clinical trial population by sex, race, and gender. Declarations of interest: none Sars-CoV-2 in pregnancy: Why is it better than expected? Clinical Characteristics of Pregnant Women with COVID-19 in Wuhan, China Update: Characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status-United States Characteristics and Maternal and Birth Outcomes of Hospitalized Women with Laboratory 13 States Site of delivery contribution to black-white severe maternal morbidity disparity Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections, medRxiv Detection of SARS-CoV-2 in Different Types of Clinical Specimens Direct Link Van den Bruel A. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis RT-PCR tests for SARS-CoV-2 processed at a large Italian Hospital and false-negative results among confirmed COVID-19 cases FDA Briefing Document. Pfizer-BioNTech COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting FDA Briefing Document. Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting FDA Briefing Document. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Vaccines and Related Biological Products Advisory Committee Meeting Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons Content source: National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. 20. ACOG Committee Opinion No. 732 Summary: Influenza Vaccination During Pregnancy Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections, medRxiv Detection of SARS-CoV-2 in Different Types of Clinical Specimens Van den Bruel A. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis MOA mechanism of action; EUA Emergency Use Authorization; * Efficacy refers to prevention of COVID-19 (positive COVID test) in the study population 7 or more days after second dose Pfizer vaccine, 14 or more days after second dose Moderna vaccine, and prevention of moderate to severe COVID-19, 2 and 4 weeks after Janssen vaccine FDA Briefing Document. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Vaccines and Related Biological Products Advisory Committee Meeting Legend for Table 2