COVID-19: Uncertainties from Conception to Birth

Abstract

Scientific information on the impact of the new coronavirus (SARS-CoV-2) on the health of pregnant women, fetuses and newborns is considered of limited confidence, lacking good-quality evidence, and drawing biased conclusions. As a matter of fact, the initial impressions that the evolution of COVID-19 was no different between pregnant and non-pregnant women, and that SARS-CoV-2 was not vertically transmitted, are confronted by the documentation of worsening of the disease during pregnancy, poor obstetric outcomes, and the possibility of vertical transmission. The present article aims to compile the data available on the association of COVID-19 and reproductive events, from conception to birth.

Resumo

As informações científicas sobre o impacto do novo coronavírus, SARS-CoV-2, na saúde de gestantes, fetos e recém-nascidos são consideradas de confiabilidade limitada, sem evidências de boa qualidade, e levam a conclusões enviesadas. De fato, as impressões iniciais de que a evolução da Covid-19 não era diferente entre mulheres grávidas e não grávidas, e de que o SARS-CoV-2 não era transmitido verticalmente, são confrontadas pela documentação de agravamentos da doença durante a gravidez, resultados obstétricos negativos, e a possibilidade de transmissão vertical. Este artigo tem como objetivo compilar os dados disponíveis sobre a associação entre a Covid-19 e os eventos reprodutivos, desde a concepção até o nascimento.

Keywords

COVID-19 - severe acute respiratory syndrome coronavirus 2 - ovary - testis - conception - pregnancy

Palavras-chave

Covid-19 - síndrome respiratória aguda grave pelo coronavírus 2 - ovário - testículo - concepção - gravidez

Publication History

Received: 21 August 2020

Accepted: 26 October 2020

Article published online:
29 January 2021

• References

• 1 World Health Organization. Pneumonia of unknown cause – China [Internet]. 2020 [cited 2020 Jul 21]. Available from: https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/
• 2 World Health Organization. Coronavirus disease (COVID-19): situation report – 209 [Internet]. 2020 [cited 2020 Aug 21]. Available from: https://apps.who.int/iris/handle/10665/333897
• 3 Ministério da Saúde. COVID-19 no Brasil [Internet]. 2020 [cited 2020 Aug 16]. Available from: https://susanalitico.saude.gov.br/extensions/covid-19_html/covid-19_html.html#/dashboard/
• 4 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W. et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395 (10226): 809-815 DOI: 10.1016/S0140-6736(20)30360-3.
• 5 Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, Zheng C. Pregnancy and perinatal outcomes of women with Coronavirus Disease (COVID-19) pneumonia: a preliminary analysis. AJR Am J Roentgenol 2020; 215 (01) 127-132 DOI: 10.2214/AJR.20.23072.
• 6 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X. et al. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis 2020; 20 (05) 559-564 DOI: 10.1016/S1473-3099(20)30176-6.
• 7 Schwartz DA. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes. Arch Pathol Lab Med 2020; ••• DOI: 10.5858/arpa.2020-0901-SA. [ahead of print]
• 8 Yu N, Li W, Kang Q, Zeng W, Feng L, Wu J. No SARS-CoV-2 detected in amniotic fluid in mid-pregnancy. Lancet Infect Dis 2020; •••: S1473-3099(20)30320-0 DOI: 10.1016/S1473-3099(20)30320-0. [ahead of print]
• 9 San-Juan R, Barbero P, Fernández-Ruiz M, López-Medrano F, Lizasoáin M, Hernández-Jiménez P. et al. Incidence and clinical profiles of COVID-19 pneumonia in pregnant women: A single-centre cohort study from Spain. EClinicalMedicine 2020; 23: 100407 DOI: 10.1016/j.eclinm.2020.100407.
• 10 Takemoto MLS, Menezes MO, Andreucci CB, Nakamura-Pereira M, Amorim MMR, Katz L, Knobel R. The tragedy of COVID-19 in Brazil: 124 maternal deaths and counting. Int J Gynaecol Obstet 2020; ••• DOI: 10.1002/ijgo.13300. [ahead of print]
• 11 Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies. Acta Obstet Gynecol Scand 2020; 99 (07) 823-829 DOI: 10.1111/aogs.13867.
• 12 Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD. et al. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (25) 769-775 DOI: 10.15585/mmwr.mm6925a1.
• 13 Sentilhes L, De Marcillac F, Jouffrieau C, Kuhn P, Thuet V, Hansmann Y. et al. Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth. Am J Obstet Gynecol 2020; •••: S0002-9378(20)30639-6 DOI: 10.1016/j.ajog.2020.06.022. [ahead of print]
• 14 Baud D, Greub G, Favre G, Gengler C, Jaton K, Dubruc E, Pomar L. Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection. JAMA 2020; 323 (21) 2198-2200 DOI: 10.1001/jama.2020.7233.
• 15 Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental Pathology in COVID-19. Am J Clin Pathol 2020; 154 (01) 23-32 DOI: 10.1093/ajcp/aqaa089.
• 16 Richtmann R, Torloni MR, Oyamada Otani AR, Levi JE, Tobara MC, Silva CA. et al. Fetal deaths in pregnancies with SARS-CoV-2 infection in Brazil: A case series. Case Rep Womens Health 2020; 27: e00243 DOI: 10.1016/j.crwh.2020.e00243.
• 17 Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W, Long X. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA 2020; 323 (18) 1848-1849 DOI: 10.1001/jama.2020.4861.
• 18 Dong L, Tian J, He S, Zhu C, Wang J, Liu C, Yang J. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA 2020; 323 (18) 1846-1848 DOI: 10.1001/jama.2020.4621.
• 19 Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do Cao J, Benachi A, De Luca D. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 2020; 11 (01) 3572 DOI: 10.1038/s41467-020-17436-6.
• 20 Patanè L, Morotti D, Giunta MR, Cristina Sigismondi C, Piccoli MG, Frigerio L. et al. Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth. Am J Obstet Gynecol MFM 2020; 2 (03) 100145 DOI: 10.1016/j.ajogmf.2020.100145.
• 21 Rasmussen SA, Jamieson DJ. Caring for women who are planning a pregnancy, pregnant, or postpartum during the COVID-19 pandemic. JAMA 2020; 324 (02) 190-191 DOI: 10.1001/jama.2020.8883.
• 22 Stanley KE, Thomas E, Leaver M, Wells D. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertil Steril 2020; 114 (01) 33-43 DOI: 10.1016/j.fertnstert.2020.05.001.
• 23 Jing Y, Run-Qian L, Hao-Ran W, Hao-Ran C, Ya-Bin L, Yang G, Fei C. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol Hum Reprod 2020; 26 (06) 367-373 DOI: 10.1093/molehr/gaaa030.
• 24 Chadchan SB, Maurya VK, Popli P, Kommagani R. The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization. bioRxiv 2020; 2020.06.23.168252 . Preprint DOI: 10.1101/2020.06.23.168252.
• 25 Fan C, Li K, Ding Y, Lu WL, Wang J. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. Medrxiv 2020
• 26 Entezami F, Samama M, Dejucq-Rainsford N, Bujan L. SARS-CoV-2 and human reproduction: An open question. EClinicalMedicine 2020; 25: 100473 DOI: 10.1016/j.eclinm.2020.100473.
• 27 Segars J, Katler Q, McQueen DB, Kotlyar A, Glenn T, Knight Z. et al; American Society for Reproductive Medicine Coronavirus/COVID-19 Task Force. Prior and novel coronaviruses, Coronavirus Disease 2019 (COVID-19), and human reproduction: what is known?. Fertil Steril 2020; 113 (06) 1140-1149 DOI: 10.1016/j.fertnstert.2020.04.025.
• 28 Xu J, Qi L, Chi X, Yang J, Wei X, Gong E. et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod 2006; 74 (02) 410-416 DOI: 10.1095/biolreprod.105.044776.
• 29 Dutta S, Sengupta P. SARS-CoV-2 and male infertility: possible multifaceted pathology. Reprod Sci 2020; ••• DOI: 10.1007/s43032-020-00261-z. [ahead of print]
• 30 Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H. et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 2004; 203 (02) 622-630 DOI: 10.1002/path.1560.
• 31 Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with Coronavirus Disease 2019. JAMA Netw Open 2020; 3 (05) e208292 DOI: 10.1001/jamanetworkopen.2020.8292.
• 32 Paoli D, Pallotti F, Colangelo S, Basilico F, Mazzuti L, Turriziani O. et al. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J Endocrinol Invest 2020; ••• DOI: 10.1007/s40618-020-01261-1. [ahead of print]
• 33 Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP. et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril 2020; 113 (06) 1135-1139 DOI: 10.1016/j.fertnstert.2020.04.024.
• 34 Wong SF, Chow KM, Leung TN, Ng WF, Ng TK, Shek CC. et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004; 191 (01) 292-297 DOI: 10.1016/j.ajog.2003.11.019.
• 35 Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection during pregnancy: Report of two cases & review of the literature. J Microbiol Immunol Infect 2019; 52 (03) 501-503 DOI: 10.1016/j.jmii.2018.04.005.
• 36 Liu H, Wang LL, Zhao SJ, Kwak-Kim J, Mor G, Liao AH. Why are pregnant women susceptible to COVID-19? An immunological viewpoint. J Reprod Immunol 2020; 139: 103122 DOI: 10.1016/j.jri.2020.103122.
• 37 Centers for Disease Control and Prevention. Assessing risk factors for severe COVID-19 illness [Internet]. 2020 [cited 2020 Jul 26]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/assessing-risk-factors.html
• 38 Trapani Júnior A, Vanhoni LR, Silveira SK, Marcolin AC. Childbirth, puerperium and abortion care protocol during the COVID-19 pandemic. Rev Bras Ginecol Obstet 2020; 42 (06) 349-355 DOI: 10.1055/s-0040-1713587.
• 39 Lopes de Sousa AF, Carvalho HEF, Oliveira LB, Schneider G, Camargo ELS, Watanabe E. et al. Effects of COVID-19 infection during pregnancy and neonatal prognosis: what is the evidence?. Int J Environ Res Public Health 2020; 17 (11) E4176 DOI: 10.3390/ijerph17114176.
• 40 Api O, Sen C, Debska M, Saccone G, D'Antonio F, Volpe N. et al. Clinical management of coronavirus disease 2019 (COVID-19) in pregnancy: recommendations of WAPM-World Association of Perinatal Medicine. J Perinat Med 2020;•••:/j/jpme.ahead-of-print/jpm-2020-0265/jpm-2020-0265.xml 10.1515/jpm-2020-0265 [ahead of print]
• 41 Della Gatta AN, Rizzo R, Pilu G, Simonazzi G. Coronavirus disease 2019 during pregnancy: a systematic review of reported cases. Am J Obstet Gynecol 2020; 223 (01) 36-41 DOI: 10.1016/j.ajog.2020.04.013.
• 42 Di Mascio D, Khalil A, Saccone G, Rizzo G, Buca D, Liberati M. et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020; 2 (02) 100107 DOI: 10.1016/j.ajogmf.2020.100107.
• 43 Antoun L, Taweel NE, Ahmed I, Patni S, Honest H. Maternal COVID-19 infection, clinical characteristics, pregnancy, and neonatal outcome: A prospective cohort study. Eur J Obstet Gynecol Reprod Biol 2020; 252: 559-562 DOI: 10.1016/j.ejogrb.2020.07.008.
• 44 Gagneur A, Dirson E, Audebert S, Vallet S, Quillien MCL, Baron R. et al. Transmission maternofoetale des coronavirus humains. Etude prospective pilote. Pathol Biol (Paris) 2007; 55 (10) 525-530 DOI: 10.1016/j.patbio.2007.07.013.
• 45 Gagneur A, Dirson E, Audebert S, Vallet S, Legrand-Quillien MC, Laurent Y. et al. Materno-fetal transmission of human coronaviruses: a prospective pilot study. Eur J Clin Microbiol Infect Dis 2008; 27 (09) 863-866 DOI: 10.1007/s10096-008-0505-7.
• 46 Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan) Coronavirus 2019-nCoV (SARS-CoV-2) infecting pregnant women: lessons from SARS, MERS, and other human Coronavirus infections. Viruses 2020; 12 (02) 194 DOI: 10.3390/v12020194.
• 47 Liu W, Wang J, Li W, Zhou Z, Liu S, Rong Z. Clinical characteristics of 19 neonates born to mothers with COVID-19. Front Med 2020; 14 (02) 193-198 DOI: 10.1007/s11684-020-0772-y.
• 48 Smithgall MC, Liu-Jarin X, Hamele-Bena D, Cimic A, Mourad M, Debelenko L, Chen X. Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization. Histopathology 2020; ••• DOI: 10.1111/his.14215. [ahead of print]
• 49 Alzamora MC, Paredes T, Caceres D, Webb CM, Valdez LM, La Rosa M. Severe COVID-19 during pregnancy and possible vertical transmission. Am J Perinatol 2020; 37 (08) 861-865 DOI: 10.1055/s-0040-1710050.
• 50 Kirtsman M, Diambomba Y, Poutanen SM, Malinowski AK, Vlachodimitropoulou E, Parks WT. et al. Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. CMAJ 2020; 192 (24) E647-E650 DOI: 10.1503/cmaj.200821.
• 51 Zhang ZJ, Yu XJ, Fu T, Liu Y, Jiang Y, Yang BX, Bi Y. et al. Novel coronavirus infection in newborn babies aged <28 days in China. Eur Respir J 2020; 55 (06) 2000697 DOI: 10.1183/13993003.00697-2020.
• 52 Hu X, Gao J, Luo X, Feng L, Liu W, Chen J. et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vertical transmission in neonates born to mothers with Coronavirus Disease 2019 (COVID-19) pneumonia. Obstet Gynecol 2020; 136 (01) 65-67 DOI: 10.1097/AOG.0000000000003926.
• 53 Maternal-fetal vertical SARS-CoV2 transmission cannot be dismissed. ESHRE Annual Meeting 2020 [cited 2020 Jul 26]. Available from: https://www.focusonreproduction.eu/article/ESHRE-News-Annual-Meeting-2020-Bahadur
• 54 Li M, Chen L, Zhang J, Xiong C, Li X. The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLoS One 2020; 15 (04) e0230295 DOI: 10.1371/journal.pone.0230295.
• 55 Freiesleben NLC, Egerup P, Hviid KVR, Severinsen ER, Kolte AM, Westergaard D. et al. SARS-CoV-2 in first trimester pregnancy - does it affect the fetus?. Medrxiv 2020
• 56 Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB. et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 2017; 171 (03) 288-295 DOI: 10.1001/jamapediatrics.2016.3982.
• 57 Penfield CA, Brubaker SG, Limaye MA, Lighter J, Ratner AJ, Thomas KM. et al. Detection of severe acute respiratory syndrome coronavirus 2 in placental and fetal membrane samples. Am J Obstet Gynecol MFM 2020; 2 (03) 100133 DOI: 10.1016/j.ajogmf.2020.100133.
• 58 Walker KF, O'Donoghue K, Grace N, Dorling J, Comeau JL, Li W, Thornton JG. Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG 2020; 127 (11) 1324-1336 DOI: 10.1111/1471-0528.16362.
• 59 Philip RK, Purtill H, Reidy E. et al. Reduction in preterm births during the COVID-19 lockdown in Ireland: a natural experiment allowing analysis of data from the prior two decades. Medrxiv 2020
• 60 Hedermann G, Hedley PL, Bækvad-Hansen M, Hjalgrim H, Rostgaard K, Poorisrisak P. et al. Danish premature birth rates during the COVID-19 lockdown. Arch Dis Child Fetal Neonatal Ed 2020: fetalneonatal-2020-319990
• 61 Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005; 353 (01) 64-73 DOI: 10.1056/NEJMra043475.
• 62 Heffner LJ. Advanced maternal age--how old is too old?. N Engl J Med 2004; 351 (19) 1927-1929 DOI: 10.1056/NEJMp048087.
• 63 Habbema JD, Eijkemans MJ, Leridon H, te Velde ER. Realizing a desired family size: when should couples start?. Hum Reprod 2015; 30 (09) 2215-2221 DOI: 10.1093/humrep/dev148.
• 64 Eijkemans MJC, Kersten FAM, Lintsen AME, Hunault CC, Bouwmans CAM, Hakkaart-van-Roijen L. et al. Cost-effectiveness of ‘immediate IVF’ versus ‘delayed IVF’: a prospective study. Hum Reprod 2017; 32 (05) 999-1008 DOI: 10.1093/humrep/dex018.
• 65 Romanski PA, Bortoletto P, Rosenwaks Z, Schattman GL. Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve. Hum Reprod 2020; 35 (07) 1630-1636 DOI: 10.1093/humrep/deaa137.
• 66 Carvalho BR, Rosa-E-Silva ACJS, Ferriani RA, Reis RMD, Silva de Sá MF. COVID-19 and assisted reproduction: a point of view on the Brazilian scenario. Rev Bras Ginecol Obstet 2020; 42 (06) 305-309 DOI: 10.1055/s-0040-1713795.
• 67 Papathanasiou A. COVID-19 screening during fertility treatment: how do guidelines compare against each other?. J Assist Reprod Genet 2020; 37 (08) 1831-1835 DOI: 10.1007/s10815-020-01885-5.
• 68 Oxford-Horrey C, Savage M, Prabhu M, Abramovitz S, Griffin K, LaFond E. et al. Putting it all together: clinical considerations in the care of critically ill obstetric patients with COVID-19. Am J Perinatol 2020; 37 (10) 1044-1051 DOI: 10.1055/s-0040-1713121.
• 69 Takemoto M, Menezes MO, Andreucci CB, Knobel R, Sousa L, Katz L. et al; Brazilian Group for Studies of COVID-19 and Pregnancy. Clinical characteristics and risk factors for mortality in obstetric patients with severe COVID-19 in Brazil: a surveillance database analysis. BJOG 2020; ••• DOI: 10.1111/1471-0528.16470. [ahead of print]
• 70 Martínez-Perez O, Vouga M, Cruz Melguizo S, Acebal LF, Panchaud A, Muñoz-Chápuli M, Baud D. et al. Association between mode of delivery among pregnant women with covid-19 and maternal and neonatal outcomes in Spain. JAMA 2020; 324 (03) 296-299 DOI: 10.1001/jama.2020.10125.
• 71 Cosma S, Borella F, Carosso A, Sciarrone A, Cusato J, Corcione S. et al. The “scar” of a pandemic: Cumulative incidence of COVID-19 during the first trimester of pregnancy. J Med Virol 2020; ••• DOI: 10.1002/jmv.26267. [ahead of print]
• 72 Sutton D, Fuchs K, D'Alton M, Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. N Engl J Med 2020; 382 (22) 2163-2164 DOI: 10.1056/NEJMc2009316.
• 73 Fassett MJ, Lurvey LD, Yasumura L, Nguyen M, Colli JJ, Volodarskiy M. et al. Universal SARS-Cov-2 screening in women admitted for delivery in a large managed care organization. Am J Perinatol 2020; 37 (11) 1110-1114 DOI: 10.1055/s-0040-1714060.
• 74 Heath PT, Le Doare K, Khalil A. Inclusion of pregnant women in COVID-19 vaccine development. Lancet Infect Dis 2020; 20 (09) 1007-1008 DOI: 10.1016/S1473-3099(20)30638-1.