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 Table of Contents 
REVIEW ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 9  |  Page : 4536-4540  

COVID-19 in pregnancy: A review


Department of Medicine, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission27-Apr-2020
Date of Decision11-Jun-2020
Date of Acceptance19-Jul-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Atul Kakar
Gangaram Institute of Medical Education and Reseacrh, New Delhi 110 060
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_714_20

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  Abstract 


COVID-19 has led on to a global healthcare crisis, similar to none in the recent past. Special emphasis must be laid on the status of pregnant women amid this outbreak, considering the vulnerability seen in pregnant women toward previous coronavirus diseases. In this review, we will try to elicit the correlation between the complications of previous coronavirus diseases (Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome) and COVID-19, the possibility of materno-fetal vertical transmission and the obstetric management protocol.

Keywords: COVID 19, pregnancy, outcome


How to cite this article:
Tripathi S, Gogia A, Kakar A. COVID-19 in pregnancy: A review. J Family Med Prim Care 2020;9:4536-40

How to cite this URL:
Tripathi S, Gogia A, Kakar A. COVID-19 in pregnancy: A review. J Family Med Prim Care [serial online] 2020 [cited 2020 Oct 25];9:4536-40. Available from: https://www.jfmpc.com/text.asp?2020/9/9/4536/296326




  Introduction Top


An array of atypical pneumonia cases, caused by the novel mutated β-coronavirus, were reported in Wuhan, China in December 2019. This novel virus was primarily cleped by World Health Organization (WHO) as the 2019 novel coronavirus (2019-nCoV) and later as coronavirus disease 2019 (COVID-19). Also, the Coronavirus Study Group (CSG) of the International Committee proposed to call it the SARS-CoV-2.

SARS-CoV-2 was isolated from a patient on 7 January 2020 and scientists came out with its genome sequencing.[1] As of 14th April 2020, COVID-19 had a total of 1,844,863 confirmed cases including 117,021 deaths.[2] The reproduction number (R0) value of SARS-CoV-2 was precisely derived in one study (as 2.2),[3] and as a range in another (from 1.4 to 6.5).[4] The steady growth of the COVID-19 pandemic is evident by the flared familial clusters of pneumonia and human-to-human transmission.[5]

Since there is a paucity of data available about effects of COVID-19 in pregnancy, we must trace back to other highly pathogenic coronavirus infections [i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS)] to gain astuteness into COVID-19's effect on pregnancy.

Recent viral infections have elicited consequential impact on pregnant women and their fetuses,[6] with the aggravated complications in pregnant women with H1N1 influenza virus[7] and the severe fetal effects of Zika virus, as recent examples.[8],[9]

In this review, we'll be highlighting the correlation of complications from previous coronavirus infections in pregnant women, discuss the complications of COVID-19 in pregnant women and the possible materno-fetal vertical transmission of COVID-19.


  Prior Coronavirus Infections in Pregnancy Top


Pregnancy is a known indicatory condition for aggravated risk of adverse obstetrical and neonatal outcomes from many viral infections. A whole cluster of systemic effects, which propagate the risk of complications from respiratory infections, arise due to the altered physiological and immunological state that is a typical component of pregnancy. The cardiovascular and respiratory components of these changes, along with the development of an immunological adaptation that allows the maternal body to tolerate the antigenically diverse fetus; inflate the risk towards development of severe respiratory diseases.[10] A marked risk of maternal morbidity and mortality was observed in a meta-analyses of influenza infections, when compared with non-pregnant women.[10],[11] Similar trend was associated with pregnant women who were infected with either of the two severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).[12]

Severe acute respiratory syndrome (SARS)

The SARS epidemic afflicted more than 8,000 people with close to 10% fatalities, in 26 different countries.[13] The causative agent, SARS-CoV, a coronavirus, was being transmitted via human-to-human contact, aerosolized droplets, and environmental contamination.[12],[14]

Twelve cases were reported of pregnant women with respiratory distress, among whom 3 died during gestation (fatality rate-25%).[12] SARS was evident in materno-fetal complications, like first trimester miscarriages (4/7 women); intrauterine growth restriction (IUGR) (2/5), and pre-term birth (4/5) in 2nd and 3rd trimesters.[15] It can be analyzed that in terms of clinical outcomes, pregnant women were worse hit than non-pregnant women.[12],[15],[16],[17],[18]

Several studies highlighted preventive approach of obstetric protocols during the SARS epidemic to curb transmission to pregnant women.[19],[20] Although the significance of these mediations was not quantifiably assessed, there definitely were valuable lessons that can be utilized in the approach to COVID-19.


  Middle East Respiratory Syndrome (MERS) Top


MERS was first identified in Saudi Arabia during 2012 and spread to over 27 countries both within and outside of the Arabian Peninsula.[12],[21] MERS-CoV was associated with possible zoonotic transmission, along with intra-familial transmission, with camels as primary source.

It was reported in 13 pregnant women and was associated with a medley of adverse clinical outcomes among 10 (77%) of them. Postnatal maternal mortality, premature delivery, and perinatal fetal death were among some of the most severe outcomes. Among the three deaths, the mothers expired within 2–3 weeks post-delivery. Among the babies, there was one intrauterine fetal demise, one stillbirth and one premature delivery at 25 weeks (where the neonate died 4 h post birth).[22],[23],[24],[25],[26],[27],[28],[29] Yet, vertical transmission of MERS-CoV had not been confirmed.[12]


  Complications of COVID-19 Top


The SARS-CoV-2, a non-segmented enveloped positive-sense RNA virus, is a β-coronavirus.[30] In a research project, the scientists isolated the genome of a strain of SARS-CoV-2, Wuhan-Hu-1 coronavirus (WHCV), and it was found to be 29.9 kb and reported to contain 16 non-structural proteins (NSP).[31] Another study suggested that genome of CoVs elicit varying number of open reading frames (ORFs).[32] To link with this, it has been reported that the virulence and differentiation mechanism of SARS-CoV-2 are attributed to particular mutations in NSP2 and NSP3.[33]

It is an expeditiously disseminating outbreak that has proven to have compelling effects on global health and medical groundwork. Thus, exquisite requirements of pregnant women ought to be incorporated in formulation of any plan of action. COVID-19 principally transmits through the respiratory tract via aerosolized droplets and respiratory secretions; and direct contact,[34] for a low minimal infectious dose.[35] However, [Table 1] summarizes the findings in multiple contemporary studies, which are suggestive of the complications of COVID-19 on pregnant women.
Table 1: Complications of COVID-19 on pregnant women

Click here to view


Here, we analyzed the findings of 9 contemporary studies, out of which 3 claimed that there were no fetal complications of COVID-19 and it affected pregnant women and non-pregnant women alike. Four of them suggested that it does have adverse fetal and neonatal complications. Moreover, in their report, Dong et al. presented a case where intrauterine vertical transmission of COVID-19 was possible.[44] A point that must be stressed upon is that almost all of the mothers that have been included in these studies were in their third trimester, and vertical transmission as well as fetal and neonatal complications, even in previous coronavirus infections, have been prevalent in the first two trimesters and not so much in the third trimester.


  Vertical Transmission of COVID-19 Top


As reported by Dong et al.,[44] there has been a case where the possibility of vertical transmission has be elicited, where the neonate had an increased IgM level, which indicated involvement of innate immunity of the neonate. Also, reports suggest that 2 neonates, born to COVID-19 infected mothers, tested positive for SARS-CoV-2, postpartum.[45],[46]

It is suggested that similar to SARS-CoV, SARS-CoV-2 could also be utilizing angiotensin-converting enzyme 2 (ACE2) receptors to infect humans hosts.[47] Moreover, the pathological findings of COVID-19, also similar to SARS, is diffuse alveolar damage with fibrin rich hyaline membranes and a few multi-nucleated giant cells.[48],[49]

In their extensive research, Valdés et al. reported that ACE2 receptors were detected in abundance in the materno-fetal interface, throughout pregnancy.[50] This can be correlated to the possibility of SARS-CoV-2 utilizing the ACE2 receptors present on the materno-fetal interface to vertically transmit from the mother to the fetus. This hypothesis can also explain the neonatal complications as suggested by the above-mentioned studies, due to the immunopathogenesis, as a response to the viral encounter.


  Obstetric Management in COVID-19 Top


As summarized in [Flowchart 1] by Favre et al.,[51] the principal for obstetric management of COVID-19 include rapid detection, isolation, and testing, profound preventive measures, regular monitoring of fetus as well as of uterine contractions, peculiar case-to-case delivery planning based on severity of symptoms, and appropriate post-natal measures for preventing infection. Transmission during birth via contact with infectious vaginal secretions and after birth via respiratory secretions is a concern. Thus, a mother who has confirmed COVID-19 or is a person under investigation should be isolated from her baby until the mother is free from any possible transmission danger.




  Conclusion Top


COVID-19 has proven to be a deadlier infection as compared to the previous two coronavirus-caused infection, SARS and MERS. Pregnancy is a severe physiologically stressful condition and is an indicatory state for immunosuppression and thus renders a pregnant woman more susceptible for complications of COVID-19, as compared to a non-pregnant woman. COVID-19 has been found to have adverse effects on both mother and neonate. Considering the reported fetal complications, it can be hypothesized that vertical transmission of COVID-19 is possible across the materno-fetal interface, by utilization of ACE2 receptors. Obstetric management of COVID-19 positive pregnant women is a critical process, which is essential in procuring a good prognosis for the mother and preventing infection in the neonate. Further, extensive Research is required to determine the viability of the hypothesis for vertical transmission of COVID-19 via the materno-fetal interface.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.  Back to cited text no. 1
    
2.
WHO. Coronavirus disease (COVID-2019) situation reports. 2020 [cited 2020 Mar 31]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.  Back to cited text no. 2
    
3.
Riou J, Althaus CL. Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. Euro Surveill 2020;25:2000058.  Back to cited text no. 3
    
4.
Liu Y, Gayle AA, Wilder-Smith A, Rocklov J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med 2020;27:taaa021. doi: https://doi.org/10.1093/jtm/taaa021.  Back to cited text no. 4
    
5.
Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet 2020;395:514-23.  Back to cited text no. 5
    
6.
Rasmussen SA, Hayes EB. Public health approach to emerging infections among pregnant women. Am J Public Health 2005;95:1942-4.  Back to cited text no. 6
    
7.
Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 influenza A (H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25.  Back to cited text no. 7
    
8.
Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, da Fonseca EB, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 2017;171:288-95.  Back to cited text no. 8
    
9.
Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects-Reviewing the evidence for causality. N Engl J Med 2016;374:1981-7.  Back to cited text no. 9
    
10.
Rasmussen SA, Jamieson DJ, Uyeki TM. Effects of influenza on pregnant women and infants. Am J Obstet Gynecol 2012;207:S3-S8.  Back to cited text no. 10
    
11.
Silasi M, Cardenas I, Racicot K, Kwon J-Y, Aldo P, Mor G. Viral infections during pregnancy. Am J Reprod Immunol 2015;73:199-213.  Back to cited text no. 11
    
12.
Schwartz DA, Graham AL. Potential maternal and infant outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses 2020;12:194.  Back to cited text no. 12
    
13.
Centers for Disease Control and Prevention. CDC SARS Response Timeline [cited 2020 February 25]. Available from: https://www.cdc.gov/about/history/sars/timeline.htm.  Back to cited text no. 13
    
14.
Hung LS. The SARS epidemic in Hong Kong: What lessons have we learned? J R Soc Med 2003;96:374-8.  Back to cited text no. 14
    
15.
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;191:292-7.  Back to cited text no. 15
    
16.
Lam CM, Wong SF, Leung TN, Chow KM, Yu WC, Wong TY, et al. A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. BJOG 2004;111:771-4.  Back to cited text no. 16
    
17.
Zhang JP, Wang YH, Chen LN, Zhang R, Xie YF. Clinical analysis of pregnancy in second and third trimesters complicated severe acute respiratory syndrome. Zhonghua Fu Chan Ke Za Zhi 2003;38:516-520.  Back to cited text no. 17
    
18.
Maxwell C, McGeer A, Tai KFY, Sermer M. Management guidelines for obstetric patients and neonates born to mothers with suspected or probable severe acute respiratory syndrome (SARS). J Obstet Gynaecol Can 2017;39:e130-e137.  Back to cited text no. 18
    
19.
Haines CJ, Chu YW, Chung TK. The effect of severe acute respiratory syndrome on a hospital obstetrics and gynaecology service. BJOG 2003;110:643-5.  Back to cited text no. 19
    
20.
Owolabi T, Kwolek S. Managing obstetrical patients during severe acute respiratory syndrome outbreak. J Obstet Gynaecol Can 2004;26:35-41.  Back to cited text no. 20
    
21.
World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV). Summary and literature update – as of 27 March 2014. Available from: https://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_Update_27_March_2014.pdf?ua=1.  Back to cited text no. 21
    
22.
Park MH, Kim HR, Choi DH, Sung JH, Kim JH. Emergency cesarean section in an epidemic of the middle east respiratory syndrome: A case report. Korean J Anesthesiol 2016;69:287-91.  Back to cited text no. 22
    
23.
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;52:501-3.  Back to cited text no. 23
    
24.
Alserehi H, Wali G, Alshukairi A, Alraddadi B. Impact of middle east respiratory syndrome coronavirus (MERS-CoV) on pregnancy and perinatal outcome. BMC Infect Dis 2016;16:105.  Back to cited text no. 24
    
25.
Assiri A, Abedi GR, Al Masri M, Bin Saeed A, Gerber SI, Watson JT. Middle East respiratory syndrome coronavirus infection during pregnancy: A report of 5 cases from Saudi Arabia. Clin Infect Dis 2016;63:951-3.  Back to cited text no. 25
    
26.
Malik A, El Masry KM, Ravi M, Sayed F. Middle east respiratory syndrome coronavirus during pregnancy, Abu Dhabi, United Arab Emirates, 2013. Emerg Infect Dis 2016;22:515-7.  Back to cited text no. 26
    
27.
Payne DC, Iblan I, Alqasrawi S, Al Nsour M, Rha B, Tohme RA, et al. Stillbirth during infection with Middle East respiratory syndrome coronavirus. J Infect Dis 2014;209:1870-2.  Back to cited text no. 27
    
28.
Racelis S, de los Reyes VC, Sucaldito MN, Deveraturda I, Roca JB, Tayag E. Contact tracing the first Middle East respiratory syndrome case in the Philippines, February 2015. Western Pac Surveill Response J 2015;6:3-7.  Back to cited text no. 28
    
29.
Jeong SY, Sung SI, Sung JH, Ahn SY, Kang ES, Chang YS, et al. MERS-CoV infection in a pregnant woman in Korea. J Korean Med Sci 2017;32:1717-20.  Back to cited text no. 29
    
30.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.  Back to cited text no. 30
    
31.
Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:264-9.  Back to cited text no. 31
    
32.
Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 2019;11:E59.  Back to cited text no. 32
    
33.
Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, Ciccozzi M. COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis. J Med Virol 2020;92:584-8.  Back to cited text no. 33
    
34.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199-1207.  Back to cited text no. 34
    
35.
Lee PI, Hsueh PR. Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV. J Microbiol Immunol Infect 2020;53:365-7.  Back to cited text no. 35
    
36.
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;395:809-15.  Back to cited text no. 36
    
37.
Chua MSQ, Lee JCS, Sulaiman S, Tan HK. From the frontlines of COVID-19 – How prepared are we as obstetricians: A commentary. BJOG 2020;127:786-8.  Back to cited text no. 37
    
38.
Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, et al. Pregnancy and perinatal outcomes of women with COVID- 19 pneumonia: A preliminary analysis. AJR Am J Roentgenol 2020;215:127-32.  Back to cited text no. 38
    
39.
Mardani M, Pourkaveh B. A Controversial debate: Vertical transmission of COVID-19 in pregnancy. Arch Clin Infect Dis 2020;15:e102286.  Back to cited text no. 39
    
40.
Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: What obstetricians need to know. Am J Obstet Gynecol 2020;222:415-26.  Back to cited text no. 40
    
41.
Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A case of 2019 novel coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa200.  Back to cited text no. 41
    
42.
Liang H, Acharya G. Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow? Acta Obstet Gynecol Scand 2020;99:439-42.  Back to cited text no. 42
    
43.
Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: What about pregnancies? Lancet 2020;395:e40.  Back to cited text no. 43
    
44.
Dong L, Tian J, He S, Zhu C, Wang J, Liu C, et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA 2020;323;1846-8.  Back to cited text no. 44
    
45.
Woodward A. A pregnant mother infected with the coronavirus gave birth, and her baby tested positive 30 hours later. Available from: https://www.businessinsider.com/wuhan-coronavirus-in-infant-born-from-infected- mother- 2020-2.  Back to cited text no. 45
    
46.
Murphy S. Newborn baby tests positive for coronavirus in London. Available from: https://www.theguardian.com/world/2020/mar/14/newbornn-baby-tests-positive-for- coronavirus-in-london.  Back to cited text no. 46
    
47.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;59:270-3.  Back to cited text no. 47
    
48.
Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol 2007;170:1136-47.  Back to cited text no. 48
    
49.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420-2.  Back to cited text no. 49
    
50.
Valdés G, Corthorn J, Bharadwaj MS, Joyner J, Schneider D, Brosnihan KB. Utero-placental expression of angiotensin-(1–7) and ACE2 in the pregnant guinea-pig. Reprod Biol Endocrinol 2013;11:5.  Back to cited text no. 50
    
51.
Favre G, Pomar L, Qi X, Nielsen-Saines K, Musso D, Baud D. Guidelines for pregnant women with suspected SARS-CoV-2 infection. Lancet Infectious Diseases 2020;20:652-3.  Back to cited text no. 51
    



 
 
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