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COVID-19 (SARS-CoV-2) Infection in Pregnancy - A Systematic Review
COVID-19 (SARS-CoV-2) Infection in Pregnancy - A Systematic Review
aDepartment
of Medicine, St George’s, University of London, London, UK; bFaculty of Medicine, Imperial College
London, London, UK; cDepartment of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK;
dDepartment of Integrative Biology, Faculty of Life Science, University of Liverpool, Liverpool, UK
Identification
Scholar (n = 140) (n = 198) (n = 64) through other sources
(n = 268) (n = 2)
Studies included in
quantitative synthesis
(meta-analysis)
(n = 22)
298
Author Title No. of No. of Maternal Neonatal Delivery Key summary
pregnant babies
COVID-19 complications COVID-19 symptoms outcomes premature mode
women
symptoms
Liu Coronavirus disease 3 3 Fever (2) Foetal distress None No infant was 0 CS (2) Successful maternal and
et al. [4] 2019 (COVID-19) (1) infected neonatal outcomes. Vertical
during pregnancy: a transmission of intrauterine
case series COVID-19 infection is not yet
confirmed
Cough (1) MSAF NVD (1)
Chen Clinical 9 9 Fever (7) Foetal distress None All normal 4 CS (9) Similar clinical characteristics
et al. [5] characteristics and (2) and tested of pregnant and non-pregnant
intrauterine vertical negative for women infected with
DOI: 10.1159/000509290
transmission SARS-CoV-2 COVID-19. Vertical
potential of transmission of COVID-19
COVID-19 infection infection is not yet confirmed
in nine pregnant
Cough (4) PROM (2)
women: a
Sore throat (1) Abnormal Rapid heart rate (1) 1 died after
amniotic fluid 9 days
(2)
Diarrhoea (1) Abnormal Vomiting (1) 4 still in NVD (2)
umbilical cord hospital in
(2) stable
condition
Placenta Pneumothorax (1) 9 tested
previa (1) negative for
Akhtar/Patel/Abuelgasim/Harky
2019-nCoV
Feeding intolerance,
bloating, refusing milk,
gastric bleeding (4)
Table 2 (continued)
Liu Clinical 13 10 Fever (10) PROM (1) None Stillbirth (1) 6 CS (10) Pregnant women are
et al. [7] manifestations and (3 not susceptible to SARS-CoV-2.
outcome of SARS- born This may increase maternal
Dyspnoea (3)
Fatigue (4)
Dyspnoea (1)
DOI: 10.1159/000509290
Sore throat (1) NVD (1)
Diarrhoea (1)
299
Table 2 (continued)
300
Author Title No. of No. of Maternal Neonatal Delivery Key summary
pregnant babies
COVID-19 complications COVID-19 symptoms outcomes premature mode
women
symptoms
Li Lack of vertical 1 1 Dry cough None None None 1 CS (1) Vertical transmission of
et al. [15] transmission of intrauterine COVID-19
severe acute infection is unlikely
respiratory
Nasal congestion
syndrome
(2)
coronavirus 2, China
Rash (1)
DOI: 10.1159/000509290
Chills (1) Mild pneumonia (1)
Wang A case report of 1 1 Abdominal Recovered None Infected 36 h 0 CS (1) Vertical transmission of
et al. [17] neonatal COVID 19 pain after birth but intrauterine COVID-19
infection in China remained infection is not yet confirmed
Zambrano A pregnant women 1 1 Fever No None None 1 SVD (1) Vertical transmission of
et al. [18] with COVID-19 in complications intrauterine COVID-19
Central America infection is unlikely
Dry cough
Headache
myalgia
Iqbal An uncomplicated 1 1 Fever No None None 0 NVD (1) Pregnant women had an
et al. [19] delivery in a patient complications uncomplicated vaginal delivery
with COVID-19 in
Chills
the United States
Dry cough
myalgia
Lee Emergency cesarean 1 1 Fever No None None 0 CS (1) Good maternal and foetal
et al. [20] section on severe complications outcomes have been reported
acute respiratory
Sore throat
syndrome
cough
coronavirus 2
(SARS-CoV-2)
confirmed patient
Akhtar/Patel/Abuelgasim/Harky
Table 2 (continued)
Liu Clinical and CT 41 No Fever (16) No None None No figures No figures Cautious approach should be
et al. [21] imaging features of figures complications provided provided taken to consider COVID-19
the COVID-19 provided infection diagnosis in
Fatigue (5)
Karami Mortality of a 1 1 Fever Multi-organ Cyanotic foetus Stillbirth 1 NVD Maternal and intrauterine
et al. [22] pregnant patient failure foetal death has been reported.
diagnosed with There may be a possible
COVID-19: a case association with COVID-19
report with clinical,
Myalgia Died
radiological, and
histopathological Cough
findings
Hantoush- Maternal death due 9 12 Fever (9) Death (7) Pneumonia (1) Stillbirth (5) 4 NVD (1) Potential for maternal death in
zadeh et al. to COVID-19 disease (2 sets rare cases among pregnant
[29] of twins) women with COVID-19 during
their later trimester(s)
Dry cough (9)
Dyspnoea (6)
DOI: 10.1159/000509290
7 days after
birth
Sore throat (1) Inpatient (1) 4 tested Unknown
negative for (2)
Diarrhoea
301
Dry cough
Table 2 (continued)
302
Author Title No. of No. of Maternal Neonatal Delivery Key summary
pregnant babies
COVID-19 complications COVID-19 symptoms outcomes premature mode
women
symptoms
Shanes Placental pathology 16 16 Unknown PPROM (1) Unknown 1 stillborn 0 Unknown COVID-19-infected placentas
et al. [31] in COVID-19 have an increased prevalence of
MVM. This suggests
abnormalities in oxygenation
within the intervillous space of
COVID-19 placentas may be
associated with adverse
perinatal outcomes
All neonates
tested
DOI: 10.1159/000509290
negative for
SARS-Cov-2
CS (4)
Hoarseness
malaise
Chen Clinical analysis of 5 5 Cough (2) No None None 0 CS (2) Pregnant women with
et al. [35] pregnant women complications COVID-19 need regular
with 2019 novel monitoring and observations
coronavirus
Runny nose (1) NVD (3)
pneumonia
Breslin COVID-19 in 7 2 Fever (2) AKI (1) None None 0 CS (2) Range of presentations of
et al. [36] pregnancy: early COVID-19 infection in
lessons pregnant women
Myalgia (3) Unknown
(5)
Cough (2)
Headache (2)
Akhtar/Patel/Abuelgasim/Harky
COVID-19, coronavirus disease 2019; NRDS, neonatal respiratory distress syndrome; MSAF, meconium-stained amniotic fluid; CS, caesarean section; NVD, normal vaginal delivery; MODS,
multi-organ dysfunction syndrome; PROM, premature rupture of membranes; MVM, maternal vascular malperfusion.
Most of the mothers received nasal oxygen therapy; beit there is a low probability of this happening. Accord-
however, 11 patients were reported to receive intubation ing to 1 study, pregnancy itself does not worsen the symp-
and mechanical ventilation. Many of the pregnant women toms experienced, nor the findings on a CT scan of
received antiviral and antibiotic medications. A study by COVID-19 related pneumonia [4].
Yu et al. [14] reported the use of traditional Chinese med- Given the novelty of COVID-19, not enough evidence
ications in all 7 of their patients. Maternal clinical mani- is available to conclude the definite effect of this virus
festations reported were fever (53%), cough (32%), fa- during pregnancy. Comparison to other coronavirus in-
tigue/malaise (13%), myalgia (11%), sore throat (5%), and fections, such as SARS and MERS, may provide a possible
shortness of breath (8%). Upon admission, most pregnant indication of the outcome of the COVID-19 virus process
women underwent a low-dose radiation CT scan; the re- [22, 28]. Three studies have reported no maternal com-
ports of which included unilateral/bilateral pneumonia in plications, such as postpartum COVID-19 infection and
most patients. A marked lymphopenia was also noted in preterm labour [5, 12, 14]. However, various other studies
many patients with COVID-19. The most common ma- have reported both maternal and foetal complications in-
ternal/foetal complications included intrauterine/foetal cluding preterm delivery, respiratory distress, foetal dis-
distress (14%) and premature rupture of membranes tress, and PROM [6]. Additionally, a case report pub-
(PROM) (8%). The neonatal clinical manifestations of lished in Iran has stated 1 maternal death and subse-
COVID-19 commonly included shortness of breath (6%), quently 1 intrauterine foetal death, which has been
gastrointestinal symptoms (4%), and fever (3%). directly linked to the COVID-19 infection during the
third trimester [22]. In an adjudicated case series from
Iran, 9 pregnant women diagnosed with severe COV-
Discussion ID-19 disease during their later second or third trimester
were identified. At the time of reporting, 7 of 9 died, 1 of
Impact of COVID-19 on Pregnancy 9 remained critically ill and ventilator-dependent, and 1
The health of pregnant women needs to be taken into of 9 recovered after prolonged hospitalisation [29]. More-
account during this rapidly changing coronavirus pan- over, Baud et al. [30] reported a case of miscarriage during
demic. It is important to provide critical interventions the second trimester of pregnancy in a woman with CO-
necessary for pregnant women. These carefully evaluated VID-19, which appeared to be related to placental infec-
decisions must be extensively discussed while consider- tion with SARS-CoV-2.
ing both maternal and foetal outcomes in the context of Shanes et al. [31] examined the placentas of 16 women
the potential impact of COVID-19 on the pregnancy. with severe COVID-19 infection (15 live births in the
World Health Organisation (WHO) has reported that third trimester and 1 delivered in the second trimester
there is no apparent difference in the risk of developing after intrauterine foetal demise). The study found that
clinical symptoms between non-pregnant and pregnant pregnant women who were infected with COVID-19 and
women of reproductive age [5, 26]. It seems the latter is delivered in the third trimester were more likely to have
also not at a higher risk of developing severe disease. Pa- placentas that show features of maternal vascular malp-
tients most commonly present with mild symptoms of erfusion and intervillous thrombi. No pathognomonic
the infection including fever, cough, fatigue, and short- features were identified; however, these findings suggest
ness of breath; however, some may be asymptomatic [4– abnormal maternal circulation that is associated with ad-
7, 12–20]. In a retrospective review by Liu et al. [21], a verse perinatal outcomes. These changes may reflect a
comparison of 59 patients, which included both pregnant systemic inflammatory or hypercoagulable state influ-
and non-pregnant adults, was carried out. This review re- encing placental physiology. Shanes et al. [31] notes that
ported no significant difference between the various increased antenatal surveillance for women with CO
groups regarding the development of the clinical features VID-19 may be warranted.
of SARS-CoV-2. According to the Royal College of Obstetricians and
Pregnant women undergo physiological changes, Gynaecologists (RCOG), vertical transmission from the
which lead to altered immune systems [27]. This does not woman to her baby may be possible, as suggested by new
necessarily make them more susceptible to viral infection; evidence [27]. A few emerging studies have reported the
hence, their response to COVID-19 may be similar to any probability of in utero COVID-19 transmission by mea-
other viral infection. However, due to the modulated im- suring the foetal IgM blood level [16, 23, 32]. The IgM
mune system, they may experience severe symptoms, al- antibody is not transferred via the placenta; therefore, it
Author Contributions
Conclusion
H.A.: planned the work, conducted literature search, wrote the
manuscript, reported the work, and responsible for the overall
Given the novelty of COVID-19, data on the effect of work content. C.P.: planned the work, conducted literature search,
COVID-19 on pregnancy, the foetus, and the newborn wrote the manuscript, reported the work, and responsible for the
are so far limited to a few small case series. Nevertheless, overall work content. E.A.: planned the work, conducted literature
while pregnant women do better than the population search, wrote the manuscript, reported the work, and responsible
for the overall work content. A.H.: planned the work, supervised
aged 80 years and above, they have twice the higher rate the literature search, reviewed and edited the written manuscript,
of PPROM and 3 times the higher rate of preterm births supervised the reported work, and responsible for the overall work
compared to the general pregnant population. There is content.
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