Skip to content
Publicly Available Published by De Gruyter October 2, 2020

COVID-19 during pregnancy: an overview of maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases described in 15 countries

  • Ernesto Antonio Figueiro-Filho ORCID logo EMAIL logo , Mark Yudin and Dan Farine

Abstract

The objective of this review was to identify the most significant studies reporting on COVID-19 during pregnancy and to provide an overview of SARS-CoV-2 infection in pregnant women and perinatal outcomes. Eligibility criteria included all reports, reviews; case series with more than 100 individuals and that reported at least three of the following: maternal characteristics, maternal COVID-19 clinical presentation, pregnancy outcomes, maternal outcomes and/or neonatal/perinatal outcomes. We included eight studies that met the inclusion criteria, representing 10,966 cases distributed in 15 countries around the world until July 20, 2020. The results of our review demonstrate that the maternal characteristics, clinical symptoms, maternal and neonatal outcomes almost 11,000 cases of COVID-19 and pregnancy described in 15 different countries are not worse or different from the general population. We suggest that pregnant women are not more affected by the respiratory complications of COVID-19, when compared to the outcomes described in the general population. We also suggest that the important gestational shift Th1-Th2 immune response, known as a potential contributor to the severity in cases of viral infections during pregnancy, are counter-regulated by the enhanced-pregnancy-induced ACE2-Ang-(1–7) axis. Moreover, the relatively small number of reported cases during pregnancy does not allow us to affirm that COVID-19 is more aggressive during pregnancy. Conversely, we also suggest, that down-regulation of ACE2 receptors induced by SARS-CoV-2 cell entry might have been detrimental in subjects with pre-existing ACE2 deficiency associated with pregnancy. This association might explain the worse perinatal outcomes described in the literature.

Introduction

Zoonoses are diseases in which transmission from animals to humans can occur [1], [2], mostly due to the increase in human population, the expansion of commercial and scientific-technological activities to rural areas and the invasion of wild habitats by humans [3]. It was previously described that 60% of human infectious diseases arise from animal transmission [2]. Zoonoses can represent a real threat to human lives, as seen in previous pandemics with world wide spread, with the potential for high mortality rates [1], [2], [4]. Seven different bat-borne viruses have caused world-wide outbreaks since 1994: Hendra in 1994, Nipah in 1998, Marburgh virus in 1998 and 2004, SARS in 2002, MERS in 2012, Ebola in 2014 and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused by the novel Coronavirus 2019, also called COVID-19, in 2019 [5]. Other incidents include the H5/N1 avian influenza outbreak in 2005, H1/N1 influenza “swine-flu” pandemic in 2009, and the West African Ebola outbreak in 2013 and 2016 [2], [3].

The first stage of a pandemic caused by zoonotic agents, like SARS-CoV-2, is called spillover, when the virus jumps from wild animals to humans [3]. There are four stages that are required for zoonotic agents to emerge in humans: 1) human contact with the infectious agent; 2) cross-species transmission of the agent; 3) sustained human-to-human transmission and 4) genetic adaptation by the human host [3], [4]. All these steps occurred when COVID-19 pandemic started in Wuhan, China on late December 2019 [5], and the possible initial source of the SARS-CoV-2 virus was a species of horseshoe bat found in caves in Yunnan Province [3], [4], [6], [7]. It was also identified that secondary or intermediate hosts in which SARS-CoV-2 lived prior to reaching humans were likely the pangolins [8]. After the sustained human-to-human transmission was identified and the virus was adapted to humans, international outbreaks of COVID-19 were reported in South Korea, Iran, and Italy and the virus then rapidly spread worldwide [9], [10], [11].

As of July 20 2020, the COVID-19 pandemic had caused almost 15 million (14,938,874) people infections worldwide with more than 615,000 deaths (4.1%) in 188 countries (https://coronavirus.jhu.edu/map.html). The total number of people infected so far by SARS-CoV-2 virus represents approximately 0.2% of world population (15 million/7.8 billion). The objective of this review was to identify the most significant studies reporting on COVID-19 during pregnancy and to provide an overview of SARS-CoV-2 infection in pregnant women and perinatal outcomes.

Materials and methods

We conducted a comprehensive literature search using PubMed, EMBASE, Cochrane Library and Google Scholar until July 20, 2020. We used the combination of the following terms: SARS-CoV-2, COVID-19, coronavirus 2019, pregnancy, gestation, maternal, perinatal, fetal, outcomes, vertical transmission, neonatal, mortality and morbidity. Titles and abstracts were reviewed by all authors to evaluate their relevance for our study. Eligibility criteria included all reports, reviews, case series with:

  1. More than 100 individuals and

  2. Reported at least three of the following criteria and/or sub-criteria:

    1. Maternal characteristics (age, BMI, race-ethnicity, comorbidities).

    2. Maternal COVID-19 clinical presentation (symptoms, radiological and laboratory findings);

    3. Pregnancy Outcomes (gestational age at diagnosis, gestational age at delivery, mode of delivery);

    4. Maternal Outcomes (ICU admission, respiratory support, hospitalization, recovered cases, maternal death);

    5. Neonatal/Perinatal Outcomes (live birth, birth weight, gestational age at delivery, apgar, preterm birth, newborn complications, neonatal hospitalization, fetal demise/Stillbirth, SARS-CoV-2-positive tests).

Once we defined the published/accepted articles that met these criteria, we performed a detailed analysis of the papers and we plotted the information on Tables. We added all reported cases to extract as much as possible the absolute and relative values of each analyzed parameter.

Results

We included eight studies [12], [13], [14], [15], [16], [17], [18], [19] that met the inclusion criteria as shown in Table 1, representing 10,966 cases. The studies included were: three Systematic Reviews [12], [13], [14], one Systematic Review & Meta-Analysis [15], 2 Case Series [16], [17], one Population-based Epidemiological Report [18] and one Prospective Cohort Study [19]. The prospective cohort described the perinatal outcomes of COVID-19 and pregnancy in 241 women from New York (USA) [19] and the North-American population report described main outcomes in 8,207 pregnant women in the USA with COVID-19 [18]. One case series of 617 women from France [17] and another with 978 Brazilian pregnant individuals [20] were also included in the analysis. The remaining four studies were systematic reviews of 108 [12], 136 [15], 324 [14] and 385 [13] cases of pregnancies with COVID-19. All papers together represented the total of 10,996 women reported with COVID-19 during pregnancy, distributed in 15 countries around the world (Figure 1) until July 20 2020.

Table 1:

Details on the studies included.

 Zaigham & Andersson 2020 (n=108) [12]Khoury et al. 2020 (n=241) [19]Kayem et al. 2020 (n=617) [17]Elshafeey et al. 2020 (n=385) [13]Juan et al. 2020 (n=324) [14]Matar et al. 2020 (n=136) [15]Ellington et al. 2020 (n=8,207) [18]Takemoto et al. 2020 (n=978) [20]
Studies characteristics
Journal Published/Date/ReferenceActa Obstet Gynecol Scand 2020; 99:823–829Obstet & GynecolJ Gynecol Obstet Hum ReprodInt J Gynecol Obstet 2020; 150:47–52Ultrasound Obstet Gynecol 2020;56:15–27Clin Infect DisMMWR Morb Mort Wkly Rep 2020; 69:769–775Int J Gynecol Obstet
Type of StudySystematic ReviewProspective CohortCase SeriesSystematic ReviewSystematic ReviewSystematic Review and Meta-AnalysisPopulational ReportCase Series
Accepted onApril 6 2020June 3 2020May 31 2020April 23 2020May 17 2020June 16 2020June 26 2020July 9 2020
Number of articles included (Systematic Review)18NANA332424NANA
Case Series Included (n>10)4NANA1695NANA
Individual Reports Included (n<10)14NANA171519NANA
Country (ies) where Pregnancy and COVID19 cases were reportedChina, Sweden, USA, Korea, HondurasUSAFranceChina, Australia, Honduras, Iran, South Korea, Sweden, Turkey, USA, Italy, NetherlandChina, Australia, Iran, Korea, Sweden, Turkey, USA, Italy, Spain, Peru, Canada, FranceChina, Iran, South Korea, HondurasUSABrazil
Figure 1: In red, all 15 countries from where 10,996 cases of pregnant women with COVID-19 were reported until July 16 2020 (Canada, USA, Honduras, Brazil, Peru, Spain, Italy, France, Netherlands, Sweden, Turkey, Iran, China, Korea, and Australia).
Figure 1:

In red, all 15 countries from where 10,996 cases of pregnant women with COVID-19 were reported until July 16 2020 (Canada, USA, Honduras, Brazil, Peru, Spain, Italy, France, Netherlands, Sweden, Turkey, Iran, China, Korea, and Australia).

One fact that became clear was the overlapping of studies within the systematic reviews. We made a detailed analysis of all systematic reviews and we found that the review that included 385 [13] women overlapped with the previous reports of 108 [12], 136 [15] and 324 [14] women. Table 2 describes the overlapping details. Initially all reviews together described the total of 953 cases, distributed in 99 papers, mostly from China. After our analysis we identified that 70 articles were overlapping (representing 579 cases) and the actual number of cases was 374 and not 953. Although we used the information the way it was published to compile all the information hereby described, the actual number of reported pregnant women with COVID-19 during pregnancy so far is 10,417 (10,996 cases in total minus 579 overlapping cases).

Table 2:

Overlapping data along the four systematic reviews included.

Author, year (n)Zaigham & Andersson 2020 (n=108)Elshafeey et al. 2020 (n=385)Juan et al. 2020 (n=324)Matar et al. 2020 (n=136)Total (n=953)
Number of articles included1833242499
Overlapping articles = cases13 Overlapping with Elshafeey, Juan, Matar = 67 cases24 Overlapping with Zaigham & Andersson, Juan, Matar = 225 cases13 Overlapping with Elshafeey, Zaigham & Andersson, Matar = 185 cases20 Overlapping with Elshafeey, Juan, Zaigham & Andersson = 102 cases70 Articles = 579 cases
Not overlapping articles = cases5 Articles not overlapping = 41 cases9 Articles not overlapping = 160 cases11 Articles not overlapping = 139 cases4 Articles not overlapping = 34 cases29 Articles = 374 cases

When analyzing the maternal characteristics (Table 3) of all pregnant women with COVID-19 described, most patients were in their 30s, with range from 20–49 years. The American population report described that the majority of cases (4,469/8,207; 54.5%) were in the 25–34 years range. Hispanic and Latino ethnicity also represented the majority of cases (1,822/8,428; 36.5%). Known underlying medical conditions were described in 22.8% of the patients (1,905/8,343) with special attention to chronic respiratory diseases (415/2,495; 16.6%), clinical diabetes (391/3,473; 11.3%) and cardiovascular diseases (316/2,856; 11.1%).

Table 3:

Maternal characteristics of 10,966 pregnant women with COVID-19 described in 15 countries until July 20 2020.

Zaigham & Andersson 2020 (n=108)Khoury et al. 2020 (n=241)Kayem et al. 2020 (n=617)Elshafeey et al. 2020 (n=385)Juan et al. 2020 (n=324)Matar et al. 2020 (n=136)Ellington et al. 2020 (n=8,207)Takemoto et al. 2020 (n=978)Total (n=2,789; 10,996)
Maternal Characteristics
Age , years30.4± 3.632 (18–47)INA21–4220–4921.7 (25–41)INA30.5±7.2NA
Age>35 yearsINAINA194/617 (31.4%)INAINAINA1,817/8,207 (22.1%)INA2,011/8,824 (22.8%)
15–24 yearsINAINAINAINAINAINA1921/8,207 (23.4%)INA1921/8,207 (23.4%)
25–34 yearsINAINAINAINAINAINA4,469/8,207 (54.4%)INA4,469/8,207 (54.4%)
35–44 yearsINAINAINAINAINAINA1,817/8,207 (22.1%)INA1,817/8,207 (22.1%)
BMIINA30.5 (21–56)INAINAINAINAINA30.5 (21–56)
>30INA98/178 (55.0%)139/617 (22.5%)INAINAINAINA89/978 (9.1%)326/1,773 (18.4%)
30–39.9INA84/178 (47.2%)INAINAINAINAINAINA84/178 (47.2%)
>40INA14/178 (7.9%)INAINAINAINAINAINA14/178 (7.9%)
Race-Ethnicity
Asian, non-HispanicINAINAINAINAINAINA254/8,207 (3.1%)INA254/8,207 (3.1%)
Black, non-HispanicINA24/221 (10.9%)INAINAINAINA1,459/8,207 (22.1%)INA1,483/8,428 (17.5%)
White, non-HispanicINA67/221 (30.3%)INAINAINAINA1,520/8,207 (23.0%)235/978 (24.0%)1,822/9,406 (19.4%)
Hispanic or LatinoINA33/221 (14.9%)INAINAINAINA3,048/8,207 (46.2%)INA3,081/8,428 (36.5%)
Multiple or other raceINAINAINAINAINAINA321/8,207 (3.9%)743/978 (76.0%)1,064/9,185 (11.6%)
Comorbidities
Known underlying medical conditionINAINAINAINAINA27/136 (19.8%)1,878/8,207 (22.9%)INA1,905/8,343 (22.8%)
AsthmaINAINA37/617 (6%)INAINAINAINA23/978 (2.4%)60/1,595 (3.76%)
Chronic respiratory diseasesINAINA6/617 (1%)INAINAINA409/1,878 (21.8%)INA415/2,495 (16.6%)
DM 1/2INAINA14/617 (2.3%)INAINAINA288/1,878 (15.3%)89/978 (9.1%)391/3,473 (11.3%)
History of preeclampsiaINAINA27/617 (4.4%)INAINAINAINAINA27/617 (4.4%)
Cardiovascular diseaseINAINAINAINAINAINA262/1,878 (14.0%)54/978 (5.5%)316/2,856 (11.1%)
Chronic hypertension/hypertensive disorders in PINAINA18/617 (2.9%)INA11/178 (6.2%)INAINAINA29/795 (3.64%)
PreeclampsiaINAINA21/617 (3.4%)INA3/178 (1.7%)INAINAINA24/795 (3.01%)
GDMINAINA71/617 (11.5%)INA18/220 (8.2%)INAINAINA89/837 (10.6%)
HypothyroidismINAINAINAINA2/234 (0.9%)INAINAINA2/234 (0.9%)
Chronic renal diseaseINAINAINAINAINAINA12/1,878 (0.6%)INA12/1,878 (0.6%)
Chronic liver diseaseINAINAINAINAINAINA8/1,878 (0.4%)INA8/1,878 (0.4%)
Immuno compromised conditionINAINAINAINAINAINA66/1,878 (3.5%)INA66/1,878 (3.5%)
Neurological/Neurodevelopmental/intellectual DINAINAINAINAINAINA17/1,878 (0.9%)INA17/1,878 (0.9%)
Placenta previa/acretaINAINAINAINA1/38 (2.6%)INAINAINA1/38 (2.6%)
Smoking in pregnancyINAINA16/617 (2.6%)INAINAINAINAINA16/617 (2.6%)
  1. NA, not applicable; INA, information not available; DM, diabetes mellitus; GDM, gestational diabetes.

In regard to maternal COVID-19 clinical presentation, Table 4 describes the wide range of symptoms and radiological and laboratory findings in this cohort of patients during pregnancy. Most of the described pregnant women enrolled in the studies manifested symptoms (7,169/7,576; 94.6%), but with mild presentation (921/1,243; 74.1%). The symptoms that were more frequently described during pregnancy were: cough (51.8%), fever (40%) and myalgia (43%), although more than 1/3 of cases manifested a variety of other symptoms, with a special significance to loss of taste/smell in almost 20% of cases (759/4,091; 18.4%). The most common and frequent radiological sign described was patchy shadowing/ground glass opacity (88%) and laboratory results revealed reduced leukocytes (80%), elevated CRP (27%) and elevated D-dimer (22%).

Table 4:

Maternal clinical presentation, symptoms, radiological and laboratory findings of 10,966 pregnant women with COVID-19 described in 15 countries until July 20 2020.

Zaigham & Anderson 2020 (n=108)Khonry et al. 2020 (n=241)Kavem et al. 2020 (n=617)Elshafeev et al. 2020 (n=385)Juan et al. 2020 (n=324)Matar et al. 2020 (n=136)Ellington et al. 2020 (n=8.207)Takemoto et al. 2020 (n=978)Total (n=2,789; 10.996)
Maternal COVID-19 clinical presentation
AsymptomaticINA102/241 (42.3%)120/617 (19.5%)29/385 (7.5%)INAINA156/5,355 (2.9%)INA407/6,598 (6.2%)
SymptomaticINA139/241 (57.7%)497/617 (80.5%)356/385 (92.5%)INAINA5,199/5,355 (97.1%)978/978 (100%)7,169/7,576 (94.6%)
MildINA64/241 (26.5%)489/617 (79.2%)368/385 (95.6%)INAINAINAINA921/1,243 (74.1%)
SevereINA63/241 (26.1%)93/617 (15.1%)14/385 (3.6%)INAINAINAINA170/1,243 03.7%)
CriticalINA12/241 (5.0%)35/617 (5.7%)3/385 (0.8%)INAINAINAINA50/1,243 (4.0%)
Maternal COVID-19 symptoms
Fever63/92 (68%)46/139 (33.0%)285/617 (46.2%)259/385 (67.3%)138/295 (46.8%)69 136 (51%)1,190/3,474 (343%)INA2,050/5,138 (39.994)
Cough37/108 (34%)54/139 (38.8%)384/617 (62.2%)253/385 (65.7%)101/295 (34.2%)39 136 (29%)1,799/3,474 (51.8%)INA2,667/5,154 (51.7594)
Loss of taste/smellINAINA172/617 (27.9%)INAINAINA587.3,474 (16.9%)INA759/4,091 (18–494)
Malaise14/108 (13%)INAINAINA0 (0%)INAINAINA14/108 (1394)
Dyspnea13/108 (12%)19/139 (13.6%)165/617 (26.7%)28/385 (7.3%)39/295 (13.2%)7/136 (5.1%)1,045/3,474 (30.1%)INA1,303/5,154 (25.394)
Myalgia11 108 (7%)INAINA24/385 (6.2%)27/295 (92%)10/136 (7.35%)1,323/3,474 (38.1%)INA1,861/4,290 (43.494)
Sore throat8/108 (7%)INAINA27/385 (7.0%)10/295 (3.4%)5/136 (3.7%)942/3,474 (27.1%)INA984/4,290 (22.9494)
HeadacheINAINAINAINAINAINA1,409/3,474 (40.6%)INA1,409/3,474 (40.694)
Nausea/VomittingINAINAINAINAINAINA682/3,474 (19.6%)INA682/3,474 (19.694)
Diarrhea7/108 (6%)INA54617 (8.8%)28/385 (7.3%)11/295 (3 7%)7/136 (5.1%)497/3,474 (14.394)INA597/5,154 (11.6%)
FatigueINAINAINA27/385 (7.0%)28/295 (9.5%)INAINAINA55/680 (8.1%)
ChillsINAINAINA21/385 (5.5%)INAINA989/3,474 (28.594)INA989/3,474 (28.594)
Runny noseINAINAINAINAINAINA326/3,474 (9.4%)INA326/3,474 (9.494)
OtherINAINAINA<5%INAINA1,190/3,474 (343%)INA1,190/3,474 (34.394)
Symptoms during Post-PartumINAINAINA19 385 (4.9%)INAINAINA224 978 (22.9%)243/1,363 (4.994)
Radiological and laboratory findings
Patchy shadowing ground glass opacityINAINAINA102/125 (81.6%)183/190 (96.3%)111/136 (81.6%)INAINA396/451 (87.894)
No Radiological findingsINAINAINA4/125 (3.2%)7/190 (3.7%)INAINAINA11/315 (3 .4994)
Leukocytes (reduced)INAINAINAINA146/182 (80.2%)INAINAINA146/182 (80294)
Lymphocyte (reduced)INAINAINA54/385 (14.0%)85/197 (45.7%)INAINAINA139/582 (23.894)
CRP (elevated)INAINAINA72/385 (18.7%)90/197 (45.7%)INAINAINA162/592 (27.49.)
AST, ALT (elevated)INAINAINA43/385 (11.2%)5/42 (11.9%)INAINAINA48/427 (11.294)
Platelet (reduced)INAINAINA4/385 (1.0%)INAINAINAINA4/385 (1.094)
D-dimer (elevated)INAINAINA86/385 (22.3%)INAINAINAINA86/385 (22.394)
  1. NA, not applicable; INA, information not available; CRP, C-reactive protein; AST, aspartate aminostransferase; ALT, alanine aminotransferase.

With respect to pregnancy and maternal outcomes, Table 5 shows that the gestational age at diagnosis had a wide range of 6–41 weeks, with almost half of cases diagnosed from 32–36 weeks (23%) and after 37 weeks and post-partum (22.3%). This information was only available in the French report [17]. The systematic review including 385 patients [13] described that 72% of cases were diagnosed with COVID-19 with GA>24 weeks. At the time of all publications, approximately 62% (1,119/1,811) of patients had delivered, therefore this information was not available in the American population report [18], nor in the Brazilian case series [16]. Out of the patients delivered, the gestational age at delivery ranged from 28–41 w, with cesarian deliveries representing 68% (761/1,119) and vaginal births 31.2% (349/1,119). Cesarian indicated exclusively for severe COVID-19 infection was found in 28% of cases (149/531).

Table 5:

Pregnancy and Maternal Outcomes of 10,966 pregnant women with COVID-19 described in 15 countries until July 20 2020.

Zaigham & Anderson 2020 (n=108)Khoury et al. 2020 (n=617)Kayem et al. 2020 (n=617)Elshafeey et al. 2020 (n=385)Juan et al. 2020 (n=324)Matar et al. 2020 (n=136)Ellington et al. 2020 (n=8,207)Takemoto et al. 2020 (n=978)Total (2,789; 10,996)
Pregnancy outcomes
Gestational age at diagnosis36INAINA6–415–4135.1 (30–40)INANA
14–21 weeksINAINAINAINAINAINAINAINA105/617 (17.0%)
22–31 weeksMAINAINAINAINAINAINAINA238/617 (38 6%)
32–36 weeksINAINAINAINAINAINAINAINA142/617 (23.0%)
>37 weeks/post partumINAINAINAINAINAINAINA224/978 (229%)356/1,595 (213%)
Diagnosis <24 weeksINAINAINA109/385 (28%)INAINAINAINA109/385 (28%)
Diagnosis >24 weeksINAINAINA276/385 (72%)INAINAINAINA276/385 (72%)
NulliparousINA52/201 (25.9%)INAINAINAINAINAINA52/201 (25.9%)
ParousINA149/201 (74.1%)INAINAINAINAINAINA149/201 (74.1%)
Deliver at time of publication86/108 (79.6%)241/241 (100%)181/617 (29.3%)252/385 (65.5)223/324 (68.8%)136/136 (100%)INAINA1,119/1,811 (61.8%)
Gastational Age at Delivery, weeksINA39 (24.7–41.6)INA30–4128–4136.2 (30–40)INAINAINA
Cesarian79/86 (92%)100/241 (415%)132/181 (73%)175/252 (69.4%)171/223 (76.7%)104/136 (76.3%)INAINA761/1,119 (68%)
Cesarian for COVID (severe/crictical)INA44/241 (18.3%)45/181 (25%)INA60/109 (55.0%)INAINAINA149/531 (28.0%)
Spontaneous vaginal delivery7/86 (92%)136/241 (56.4%)49/181 (27%)77/252 (30.6%)48/223 (21.5%)32/136 (23.5%)INAINA349/1,119 (31.2%)
Operative deliveryINA5/241 (2.1%)INAINAINAINAINAINA5/241 (2.1%)
Indication for cesarian
Nonreassuring fetal heart/fetal distressINA23/100 (23%)INAINAINA6/114 (5.3%)INAINA29/214 (13.6%)
Failed induction of laborINA11/100 (11%)INAINAINAINAINAINA11/100 (11%)
Worsening respiratory distressINA10/100 (10%)INAINAINAINAINAINA10/100 (10%}
Active phase arrestINA5/100 (5%)INAINAINAINAINAINA5/100 (5%)
Arrest descentINA5/100 (5%)INAINAINAINAINAINA5/100 (5%)
MalpresentationINA5/100 (5%)INAINAINAINAINAINA5/100 (5%)
RepeatINA31/100 (31%)INAINAINAINAINAINA31/100 (31%)
otherINA10/100 (10%)INAINAINAINAINAINA10/100 (10%)
Pregnancy outcomes
Gestational age at Diagnosis37INAINA6–425–4235.1 (30–40)INANA
14–21 weeksINAINA105/617 (17.01%)INAINAINAINAINA105/617 (17.0%)
22–31 weeksINAINA238/617 (38.6%)INAINAINAINAINA238/617 (38.6%)
32–36 weeksINAINA142/617 (23.0%)INAINAINAINAINA142/671 (23.0%)
>37 weeks/Post-partumINAINA132/617 (21.4%)INAINAINAINA224/978 (22.9%)356/1,595 (22.3%)
Diagnosis <24 weeksINAINAINA109/385 (28%)INAINAINAINA109/385 (28%)
Diagnosis >24 weeksINAINAINA276/385 (72%)INAINAINAINA276/385 (72%)
NulliparousINA52/201 (25.9%)INAINAINAINAINAINA52/201 (25.9%)
ParousINA149/201 (74.1%)INAINAINAINAINAINA149/201 (74.1%)
  1. NA, not applicable; INA, information not available.

Maternal ICU admission was described in 3.7% of cases, with respiratory support necessary in 5.25% of cases. Maternal hospitalization occurred in 35% of cases and 84% of pregnant women recovered from COVID-19 (1,340/1,595). Maternal death was described in 1.13% of cases (144/10,987) with special attention to the Brazilian report [16] that described an alarming rate of 12.7% (124/978).

Lastly, Table 6 demonstrates the Neonatal outcomes. Live birth was present in 98% of reports, with 78% term deliveries. Preterm Birth <37 weeks was seen in 21% of cases. The majority of cases had no newborn complications, although admission to NICU was reported in almost 20% of cases. Fetal demise/stillbirth rates were 1.7% (19/11,130), neonatal death described in 0.8% (9/1,137) and SARS-COV2-Negative tests were found in 98.4% of neonates (1,098/1,116). Of note is that the neonatal information was not retrieved from all studies and some of them had no information on babies’ outcomes.

Table 6:

Neonatal outcomes of 10,966 pregnant women with COVID-19 described in 15 countries until July 20 2020.

Zaigham & Andersson 2020 (n= 108)Khoury et al. 2020 (n=241)Kayem et al. 2020 (n=617)Elshafeey et al. 2020 (n=385)Juan et al. 2020 (n=324)Matar et al. 2020 (n=126)Ellington et al. 2020 (n=8,207)Takemoto et al. 2020 (n=978)Total (n=1,811; 10,018)
Neonatal outcomes
Live Birth, g86/87 (99%)245/247 (99.2%)174/181 (96.1%)251/256 (98%)INA91/94 (96.8%)INAINA847/865 (98%)
Birth weightINA3,135 g (640–4,700 g)INA1,520–4,050gINA3,127 g (1,500–3,400 g)INAINANA
Low birth weight (<2,500 g)INAINAINA20/256 (7.8%)8/103 (7.8%)INAINAINA28/259 (11%)
Gestational age at delivery, weeksINA39 (247–41.6)INA30–4128–4136.2 (30–40)INAINANA
Apgar 5 minINA9 (0–9)INAINA7 (7–10)9 (0–9)INAINANA
TwinsINA6/241 (2.5%)INA4/252 (1.6%)INAINAINAINA10/493 (2.0%)
TermINA198/241 (82.5%)126/181 (69.6%)217/256 (84.7%)INA63/94 (67.0%)INAINA604/772 (78.2%)
Preterm birth < 37 weeksINA34/233 (14.6%)55/181 (30.3%)39/256 (15.2%)INA31/94 (33.0%)INAINA159/764 (21%)
Preterm birth < 34 weeksINA10/233 (4.3%)26/181 (14.3%)20/256 (7.8%)INAINAINAINA56/670 (8.35%)
Fetal loss 14–21 weeksINAINA5/181 (2.8%)INAINAINAINAINA5/181 (2.8%)
Preterm birth 22–31 weeksINAINA21/181 (11.6%)INAINAINAINAINA21/181 (11.6%)
Preterm birth 32–36 weeksINAINA29/181 (16%)INAINAINAINAINA29/181 (16%)
Overall preterm birth 22–36 weeksINAINA50/181 (27.6%)INAINAINAINAINA50/181 (27.6%)
MaleINA119/247 (48.2%)INAINAINAINAINAINA119/247 (48.2%)
FemaleINA128/247 (51.8%)INAINAINAINAINAINA128/247 (51.8%)
Resuscitation at DeliveryINA70/233 (30%)INAINAINAINAINAINA70/233 (30%)
Newborn complicationsINAINA
Respiratory distress syndromeINA14/241 (5.8%)INA12/256 (4.7%)2/79 (2.5%)INAINAINA28/576 (4.86%)
Complications prematurity/preterm birthINA21/241 (8.7%)INA6/256 (2.4%)INAINAINAINA27/497 (5.43%)
SepsisINA1/241 (0.4%)INAINAINAINAINAINA1/241 (0.4%)
Congenital anomalyINA8/241 (3.3%)INAINAINAINAINAINA8/241 (3.3%)
NoneINA191/241 (79.3%)INAINAINAINAINAINA191/241 (79.3%)
OtherINA14/241 (5.8%)INAINAINAINAINAINA14/241 (5.8%)
Admission neonatal intensive care unitINA61/237 (25.7%)37/190 (19.5%)8/256 (3.1%)49/173 (28.3%)28/136 (20.6%)INAINA183/992 (18.45%)
Neonatal hospitalizationINAINA
<2 daysINA153/245 (62.4%)INAINAINAINAINAINA153/245 (62.4%)
3–7 daysINA65/245 (26.5%)INAINAINAINAINAINA65/245 (26.5%)
>7 daysINA29/245 (11.8%)INAINAINAINAINAINA29/245 (11.8%)
Neonatal death1/87 (1%)0/247 (0%)1/190 (0.5%)3/256 (1.2%)1/221 (0.5%)3/136 (2.2%)INAINA9/1,137 (0.8%)
Fetal demise/stillbirth1/87 (1%)2/247 (0.8%)7/181 (3.9%)2/256 (0.8%)4/223 (1.79%)3/136 (2.2%)INAINA19/1,130 (1.7%)
SARS-COV-2-positive1/75 (1%)6/236 (2.5%)2/190 (1.1%)6/256 (2.4%)1/223 (0.5%)2/136 (1.47%)INAINA18/1,116 (1.6%)
SARS-COV-2-negative74/75 (99%)230/236 (97.5%)188/190 (98.9%)250/256 (97.6%)222/223 (99.5%)134/136 (98.5%)INAINA1,098/1,116 (98.4%)
  1. NA, not applicable; INA, information not available.

Discussion

It is not possible to identify with complete accuracy how many pregnant women have been affected within the total number of people infected by this new virus. The total number of pregnancies can be calculated with the sum of all live births, abortions, and miscarriages [21] in a determined region in a given time. In 2012, the total numbers of pregnancies described were 213.4 million, out of a global population of approximately 7.1 billion people, which represents 3% of pregnant women out of total world population [21]. If we extrapolate this information, the hypothetical number of pregnant women expected in our current world population of 7.8 billion would be 234 million (3%), with the hypothetical rate of 19.5 million pregnant women per month. Our review found almost 11,000 pregnant women with COVID-19 infection reported, which represents 0.07% of total infections until July 20, 2020 (11,000/15,000,000). The hypothetical number of total pregnancies expected in the world by the end of July (136.5 million), demonstrates that the real number of infected pregnant women by SARS-COV-2 is undoubtedly much higher than the cases hereby described. We relied exclusively on data that had been published by the time this article was written, therefore we presented the most updated number of infected pregnant women described in the literature. Due to the low numbers during pregnancy described so far, one can conclude that we cannot make clinical final decisions or definitive patient counseling based on the available information.

Overall, COVID-19 infection during pregnancy does not seem to be worse than in the general population. The report from Centers for Disease Control and Prevention (CDC) compared 8,207 cases of COVID-19 in pregnant women with 83,205 cases in non-pregnant women [18]. Although the report shows a higher number of hospitalizations among the pregnant group (31.5 vs. 5.8%), the ICU admission during pregnancy was slightly higher (1.5 vs. 0.9%) and the needing of mechanical ventilation was not higher during pregnancy (0.5%) compared to non-pregnant women (0.3%). Moreover, the death rate during pregnancy was low and not different compared to non-pregnant women (0.2% in both groups) [18].

Special attention should be given to the maternal mortality rate described in the Brazilian series [16], at 12.7% of cases (124/978). The report identified more comorbidities among the pregnant women that have died (cardiovascular disease 16.3%; diabetes 33.8%; obesity 21.3%; asthma 9.3%) compared to the pregnant group that had recovered (cardiovascular disease 6.7%; diabetes 20.8%; obesity 10.3%; asthma 5.9%). ICU admission was higher (72.3 vs. 17.5%) as well as invasive respiratory support (64 vs. 4.4%) in the group of women that died compared to those that had recovered from COVID-19 in Brazil [16]. When we put together all known underlying medical conditions found in all the pregnancies included in this review, the overall rate of comorbidities described was 22.8% (1,905/8,343) with special attention to chronic respiratory diseases (415/2,495; 16.6%), clinical diabetes (391/3,473; 11.3%) and cardiovascular diseases (316/2,856; 11.1%). These numbers are similar to the Brazilian study on its own, thus demonstrating that other external factors might be involved in justifying the higher rate of maternal mortality observed in that country. The overall maternal mortality rate found among the pregnant women included in this review was 1.13% (144/10,987).

Over the course of the pandemic, it has been clear that public health measures like lockdowns impacted positively on reducing the rates of COVID-19 virus transmission [22]. The French study included in this review had shown a higher rate of comorbidities during pregnancy, although the maternal mortality rate was 0.2% (1/617), suggesting that non-therapeutic and social distancing measures can reduce the rate of complications in specific populations [17].

The perinatal outcomes in all cases analyzed in this study were reassuring as live birth was present in 98% of reports, with majority (78%) resulting in term deliveries, with no newborn complications, and NICU admission of 20%. Fetal Demise/Stillbirth rates were low at 1.7% (19/11,130) and neonatal death described in 0.8% (9/1,137) of cases. No vertical transmission was identified in 98.4% of neonates (1,098/1,116). It is important to note that only 62% (1,119/1,811) of patients had delivered at the time of publications. Therefore, the perinatal outcomes found so far may be different once all affected pregnant women have delivered. Also, of note is that not all reports included in this review had neonatal/perinatal outcomes described.

Although many previous reports of COVID-19 during pregnancy had suggested that the pregnancy can impact negatively on the clinical course of infection [23], [24], [25], potentially bringing more maternal and perinatal complications [25], [26], the data compiled in this review might tell the opposite. It was clear from previous virus outbreaks during pregnancy, especially the 2009 H1N1 [27], [28], [29], [30] and also SARS [23], [31], [32] and MERS [23], [32], [33] that pregnancy was detrimental in defining perinatal/neonatal and maternal outcomes, when comparing pregnant to non-pregnant population.

The response to viral infections during pregnancy relies mostly on the immunological changes that occur before and during gestation, in order to accommodate the developing fetus, so that the fetal tissues are not rejected by the maternal immune system [34]. These changes are characterized mostly by elevation of humoral immune responses and suppression of cell-mediated immunity, referred to as the T-helper lymphocyte type 1-type 2 (Th1-Th2) shift [28]. Pregnancy-induced alterations in immune cells and their cytokines, disparity between maternal-fetal glycosylation of IgG, and immunoregulatory pathways have important roles in the immunomodulation during pregnancy, which might explain clinical improvements of severe COVID-19 infected pregnant women after delivery [34], [35]. During influenza infection in pregnant mice, it has been observed that there are significant changes in hormonal synthesis and regulation of progesterone, PGE2, COX2, and PGF2α expression, ultimately leading to inflammatory responses that can trigger preterm-labor and adverse fetal outcomes [28].

In order to allow the SARS-CoV-2 virus entrance into the human cell, the role of the immune system and the renin-angiotensin system (RAS) is particularly important [36]. To promote a successful entry, it is necessary to have an efficient binding of the spike (S) viral envelope protruding protein that gives the ‘corona’ like appearance, to the cellular angiotensin converting enzyme 2 (ACE2) receptors [37], [38]. ACE2 receptors are also responsible for a series of chemical events that ultimately converts angiotensin I or II (Ang I or Ang II) to angiotensin1-7 [Ang-(1–7) ] [36]. The discovery of ACE2 receptors and its effect on Ang-(1–7) added a new branch to the complexity of the RAS as a counter-regulatory system of the activity of the vasoconstrictor component (ACE-AngII-AT1 axis), amplifying the vasodilator component (ACE2-Ang-(1–7) axis) [36], [39], [40], resulting in vasodilatation, natriuresis, anti-proliferation and an increase in the bradykinin-nitric oxide (NO) system [41], [42].

Some conditions are known to be associated with some degree of ACE2 deficiency like older age, diabetes, cardiovascular disease and hypertension [36], which also represents the group of comorbidities more likely to be infected and develop more severe complications with COVID-19 infection [5]. On the other hand, it was also demonstrated that during pregnancy the expression of Ang-(1–7) is enhanced [39], thus shifting the RAS to the ACE2-Ang-(1–7) axis rather to the ACE-AngII-AT1 axis. The final effects of the ACE2-Ang-(1–7) axis are increased vasodilation, reduced fibrosis, reduced inflammation, reduced thrombosis and reduced pulmonary damage [36], [41], [42]. In theory, in a setting of reduced ACE2 receptors in consequence of SARS-CoV-2 viral invasion, the unbalanced regulation between the ACE-AngII-AT1 axis and the ACE2-Ang-(1–7) axis would contribute to enhance the progression of vasoconstriction, increased fibrosis, inflammatory and thrombotic processes [36].

Conclusions

The results of our review demonstrate that the maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases of COVID-19 and pregnancy described in 15 different countries are not worse or different from the general population. We suggest that, differently from what was previously published [26], pregnant women are not more affected by the respiratory complications of COVID-19, compared with non-pregnant available data. We also suggest that the important gestational shift Th1-Th2 immune response [34], known as a potential contributor to the severity in cases of viral infections during pregnancy [28], are counter-regulated by the enhanced-pregnancy-induced ACE2-Ang-(1–7) axis [39]. Moreover, the relatively small number of reported cases during pregnancy does not allow us to affirm that COVID-19 is more aggressive during pregnancy. Conversely, we also suggest, that down-regulation of ACE2 receptors induced by SARS-CoV-2 cell entry might have been detrimental in subjects with pre-existing ACE2 deficiency associated with pregnancy. This association might explain the worse perinatal outcomes described in the literature [26], [43], [44], [45].


Corresponding author: Ernesto Antonio Figueiro-Filho, MD, PhD, Mount Sinai Hospital, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

References

1. Morand, S, McIntyre, KM, Baylis, M. Domesticated animals and human infectious diseases of zoonotic origins: domestication time matters. Infect Genet Evol 2014;24:76–81. https://doi.org/10.1016/j.meegid.2014.02.013.Search in Google Scholar PubMed

2. Cross, AR, Baldwin, VM, Roy, S, Essex-Lopresti, AE, Prior, JL, Harmer, NJ. Zoonoses under our noses. Microb Infect 2019;21:10–19. https://doi.org/10.1016/j.micinf.2018.06.001.Search in Google Scholar PubMed PubMed Central

3. Lei, R, Qiu, R. A strategy to prevent and control zoonoses?. Hastings Cent Rep 2020;50:73–4. https://doi.org/10.1002/hast.1142.Search in Google Scholar PubMed PubMed Central

4. Childs, JE. Pre-spillover prevention of emerging zoonotic diseases: what are the targets and what are the tools?. Curr Top Microbiol Immunol 2007;315:389–443. https://doi.org/10.1007/978-3-540-70962-6_16.Search in Google Scholar PubMed PubMed Central

5. Wu, Z, McGoogan, JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease Control and prevention. J Am Med Assoc 2020;323:1239–42. https://doi.org/10.1001/jama.2020.2648.Search in Google Scholar PubMed

6. Xie, Z, Qin, Y, Li, Y, Shen, W, Zheng, Z, Liu, S. Spatial and temporal differentiation of COVID-19 epidemic spread in mainland China and its influencing factors. Sci Total Environ 2020;744:140929. https://doi.org/10.1016/j.scitotenv.2020.140929.Search in Google Scholar PubMed PubMed Central

7. Jiang, S, Du, L, Shi, Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microb Infect 2020;9:275–7. https://doi.org/10.1080/22221751.2020.1723441.Search in Google Scholar PubMed PubMed Central

8. Zhang, T, Wu, Q, Zhang, Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr Biol 2020;30:1346–51. https://doi.org/10.1016/j.cub.2020.03.022.Search in Google Scholar PubMed PubMed Central

9. Ciotti, M, Ciccozzi, M, Terrinoni, A, Jiang, WC, Wang, CB, Bernardini, S. The COVID-19 pandemic. Crit Rev Clin Lab Sci 2020;57:1–24 https://doi.org/10.1080/10408363.2020.1783198.Search in Google Scholar PubMed

10. Zhan, C, Tse, CK, Lai, Z, Hao, T, Su, J. Prediction of COVID-19 spreading profiles in South Korea, Italy and Iran by data-driven coding. PloS One 2020;15:e0234763. https://doi.org/10.1371/journal.pone.0234763.Search in Google Scholar PubMed PubMed Central

11. Kim, S, Castro, MC. Spatiotemporal pattern of COVID-19 and government response in South Korea (as of May 31, 2020). Int J Infect Dis 2020;98:328–33. https://doi.org/10.1016/j.ijid.2020.07.004.Search in Google Scholar PubMed PubMed Central

12. Zaigham, M, Andersson, O. Maternal and perinatal outcomes with COVID-19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand 2020;99:823–9. https://doi.org/10.1111/aogs.13867.Search in Google Scholar PubMed PubMed Central

13. Elshafeey, F, Magdi, R, Hindi, N, Elshebiny, M, Farrag, N, Mahdy, S, et al. A systematic scoping review of COVID-19 during pregnancy and childbirth. Int J Gynecol Obstet 2020;150:47–52. https://doi.org/10.1002/ijgo.13182.Search in Google Scholar PubMed PubMed Central

14. Juan, J, Gil, MM, Rong, Z, Zhang, Y, Yang, H, Poon, LC. Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol 2020;56:15–27. https://doi.org/10.1002/uog.22088.Search in Google Scholar PubMed PubMed Central

15. Matar, R, Alrahmani, L, Monzer, N, Debiane, LG, Berbari, E, Fares, J, et al. Clinical presentation and outcomes of pregnant women with COVID-19: a systematic review and meta-analysis. Clin Infect Dis 2020. https://doi.org/10.1093/cid/ciaa828.Search in Google Scholar PubMed PubMed Central

16. Takemoto, MLS, Menezes, MO, Andreucci, CB, Nakamura-Pereira, M, Amorim, MMR, Katz, L, et al. The tragedy of COVID-19 in Brazil: 124 maternal deaths and counting. Int J Gynecol Obstet 2020;151:154–6 https://doi.org/10.1002/ijgo.13300.Search in Google Scholar PubMed PubMed Central

17. Kayem, G, Lecarpentier, E, Deruelle, P, Bretelle, F, Azria, E, Blanc, J, et al. A snapshot of the Covid-19 pandemic among pregnant women in France. J Gynecol Obstet Hum Reprod 2020;49:101826. https://doi.org/10.1016/j.jogoh.2020.101826.Search in Google Scholar PubMed PubMed Central

18. 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;69:769–75. https://doi.org/10.15585/mmwr.mm6925a1.Search in Google Scholar PubMed PubMed Central

19. Khoury, R, Bernstein, PS, Debolt, C, Stone, J, Sutton, DM, Simpson, LL, et al. Characteristics and outcomes of 241 births to women with severe Acute respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection at five New York city medical Centers. Obstet Gynecol 2020;136:273–82. https://doi.org/10.1097/aog.0000000000004025.Search in Google Scholar PubMed

20. Takemoto, MLS, Menezes, MO, Andreucci, CB, Knobel, R, Sousa, LAR, Katz, L, et al. Maternal mortality and COVID-19. J Matern Fetal Neonatal Med 2020. https://doi.org/10.1080/14767058.2020.1786056.Search in Google Scholar PubMed

21. Sedgh, G, Singh, S, Hussain, R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann 2014;45:301–14. https://doi.org/10.1111/j.1728-4465.2014.00393.x.Search in Google Scholar PubMed PubMed Central

22. Flaxman, S, Mishra, S, Gandy, A, Unwin, HJT, Mellan, TA, Coupland, H, et al. Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe. Nature 2020;584:257–61. https://doi.org/10.1038/s41586-020-2405-7.Search in Google Scholar PubMed

23. Schwartz, DA, Graham, AL. Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections. Viruses 2020;12:194. https://doi.org/10.3390/v12020194.Search in Google Scholar PubMed PubMed Central

24. Cabero-Pérez, MJ, Gómez-Acebo, I, Dierssen-Sotos, T, Llorca, J. [Infection by SARS-CoV-2 in pregnancy and possibility of transmission to neonates: a systematic revision]. Semergen 2020;46:40–7. https://doi.org/10.1016/j.semerg.2020.06.011.Search in Google Scholar PubMed PubMed Central

25. Trocado, V, Silvestre-Machado, J, Azevedo, L, Miranda, A, Nogueira-Silva, C. Pregnancy and COVID-19: a systematic review of maternal, obstetric and neonatal outcomes. J Matern Fetal Neonatal Med 2020:1–13. https://doi.org/10.1080/14767058.2020.1781809.Search in Google Scholar PubMed

26. Silva, CRAC, Oliveira, LV, Lopes, LP, Santos, WAGD, Agra, IKR. Immunological aspects of coronavirus disease during pregnancy: an integrative review. Rev Assoc Med Bras 1992;66:696–700. https://doi.org/10.1590/1806-9282.66.5.696.Search in Google Scholar PubMed

27. Figueiro-Filho, EA, Oliveira, MLG, Pompilio, MA, Uehara, SNO, Coelho, LR, De Souza, BA, et al. Obstetric, clinical, and perinatal implications of H1N1 viral infection during pregnancy. Int J Gynecol Obstet 2012;116:214–18. https://doi.org/10.1016/j.ijgo.2011.10.026.Search in Google Scholar PubMed

28. Littauer, EQ, Esser, ES, Antao, OQ, Vassilieva, EV, Compans, RW, Skountzou, I. H1N1 influenza virus infection results in adverse pregnancy outcomes by disrupting tissue-specific hormonal regulation. PLoS Pathog 2017;13:e1006757. https://doi.org/10.1371/journal.ppat.1006757.Search in Google Scholar PubMed PubMed Central

29. Fell, DB, Platt, RW, Basso, O, Wilson, K, Kaufman, JS, Buckeridge, DL, et al. The relationship between 2009 pandemic H1N1 influenza during pregnancy and preterm birth: a population-based cohort study. Epidemiology 2018;29:107–16. https://doi.org/10.1097/ede.0000000000000753.Search in Google Scholar PubMed

30. Rasmussen, SA, Jamieson, DJ. Influenza and pregnancy: No time for complacency. Obstet Gynecol 2019;133:23–6. https://doi.org/10.1097/aog.0000000000003040.Search in Google Scholar

31. Ksiezakowska, K, Laszczyk, M, Wilczynski, J, Nowakowska, D. SARS-CoV infection and pregnancy. Ginekol Pol 2008;79:47–50.Search in Google Scholar

32. Di Mascio, D, Khalil, A, Saccone, G, Rizzo, G, Buca, D, Liberati, M, et al. Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1 -19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020;2:100107. https://doi.org/10.1016/j.ajogmf.2020.100107.Search in Google Scholar PubMed PubMed Central

33. 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. https://doi.org/10.1016/j.jmii.2018.04.005.Search in Google Scholar PubMed PubMed Central

34. Forger, F, Villiger, PM. Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity. Nat Rev Rheumatol 2020;16:113–22. https://doi.org/10.1038/s41584-019-0351-2.Search in Google Scholar PubMed

35. Oliva, M, Hsu, K, Alsamarai, S, Chavez, V, Ferrara, L. Clinical improvement of severe COVID-19 pneumonia in a pregnant patient after caesarean delivery. BMJ Case Rep 2020;13. https://doi.org/10.1136/bcr-2020-236290.Search in Google Scholar PubMed PubMed Central

36. Verdecchia, P, Cavallini, C, Spanevello, A, Angeli, F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020;76:14–20. https://doi.org/10.1016/j.ejim.2020.04.037.Search in Google Scholar PubMed PubMed Central

37. Walls, AC, Park, YJ, Tortorici, MA, Wall, A, McGuire, AT, Veesler, D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281–92. https://doi.org/10.1016/j.cell.2020.02.058.Search in Google Scholar PubMed PubMed Central

38. Hoffmann, M, Kleine-Weber, H, Schroeder, S, Kruger, N, Herrler, T, Erichsen, S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–80. https://doi.org/10.1016/j.cell.2020.02.052.Search in Google Scholar PubMed PubMed Central

39. Brosnihan, KB, Neves, LA, Joyner, J, Averill, DB, Chappell, MC, Sarao, R, et al. Enhanced renal immunocytochemical expression of ANG-(1-7) and ACE2 during pregnancy. Hypertension 2003;42:749–53. https://doi.org/10.1161/01.hyp.0000085220.53285.11.Search in Google Scholar PubMed

40. Brosnihan, KB, Neves, LA, Anton, L, Joyner, J, Valdes, G, Merrill, DC. Enhanced expression of Ang-(1-7) during pregnancy. Braz J Med Biol Res 2004;37:1255–62. https://doi.org/10.1590/s0100-879x2004000800017.Search in Google Scholar PubMed

41. Iwai, M, Horiuchi, M. Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis. Hypertens Res 2009;32:533–6. https://doi.org/10.1038/hr.2009.74.Search in Google Scholar PubMed PubMed Central

42. Santos, RAS, Sampaio, WO, Alzamora, AC, Motta-Santos, D, Alenina, N, Bader, M, et al. The ACE2/angiotensin-(1-7)/MAS Axis of the renin-angiotensin system: focus on angiotensin-(1-7). Physiol Rev 2018;98:505–53. https://doi.org/10.1152/physrev.00023.2016.Search in Google Scholar PubMed PubMed Central

43. Phoswa, WN, Khaliq, OP. Is pregnancy a risk factor of COVID-19?. Eur J Obstet Gynecol Reprod Biol 2020;252:605–9. https://doi.org/10.1016/j.ejogrb.2020.06.058.Search in Google Scholar PubMed PubMed Central

44. Verma, S, Carter, EB, Mysorekar, IU. SARS-CoV2 and pregnancy: an Invisible enemy?. Am J Reprod Immunol 2020:e13308. https://doi.org/10.1111/aji.13308.Search in Google Scholar PubMed PubMed Central

45. Tutiya, CT, Siaulys, MM, Kondo, MM, Miglioli-Galvão, L, C A Galvão, E, Pinheiro, CC, et al. Possible formation of pulmonary microthrombi in the early puerperium of pregnant women critically ill with COVID-19: two case reports. Case Rep Womens Health 2020;27:e00237. https://doi.org/10.1016/j.crwh.2020.e00237.Search in Google Scholar PubMed PubMed Central

Received: 2020-07-31
Accepted: 2020-09-17
Published Online: 2020-10-02
Published in Print: 2020-11-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1515/jpm-2020-0364/html
Scroll to top button