Editorial
Obstetric Medicine
COVID-19, variants of concern and
pregnancy outcome
Genetic variants of SARS-CoV-2 are not uncommon and have been
circulating since the beginning of the COVID-19 pandemic. These
variants contain mutations which arise naturally through viral repli-
cation, and may affect important pathogenic components of the
virus, such as the receptor-binding domain of the spike protein.
Some of these variants produce virus which is more infectious and
may spread more easily through the population. Those variants asso-
ciated with evidence of increased transmissibility, severity, or possible
immune evasion have been termed ‘variants of concern’ (VOCs), and
they usually rapidly replace previous viral lineages in a population.1
The United Kingdom identified a VOC called B.1.1.7 (new WHO
terminology: variant Alpha2) in the latter half of 2020, which spreads
more easily than other variants. In South Africa, another VOC called
B.1.351 (variant Beta) was detected in early October 2020, which
shares some mutations with B.1.1.7. A VOC named P.1 (variant
Gamma) emerged that was first identified in early January 2021, in
travelers from Brazil screened at an airport in Japan. This variant
contains additional mutations that may affect its ability to be recog-
nized by antibodies. Three sublineages have been identified of a var-
iant first identified in India in October 2020 (B.671.1). These include
B.1.617.2 (variant Delta) and B.1.617.3 (variant Kappa) which have
increased significantly since February 2021. The Delta variant
appears to be far more transmissible than the Alpha variant, taking
over as the predominant variant in many parts of the UK and other
countries due to increased transmissibility; investigations of its asso-
ciation with increased disease severity are ongoing.
How do these COVID-19 variants impact the pregnant individu-
al? At the beginning of the COVID-19 pandemic, there was consid-
erable concern that pregnant women would experience more severe
disease, as has been the case in influenza pandemics3 as well as severe
acute respiratory syndrome (SARS) and Middle East respiratory syn-
drome (MERS). Early reports did not show an increase in mortality
among pregnant women, although hospitalizations and ICU admis-
sion were increased.4 More recently, among all studies included in a
living systematic review,5 the risks of ICU admission (4.2% vs. 0.1%)
and mortality (0.8% vs. 0.2%) were higher in pregnant women with
COVID-19 compared to pregnant women without COVID-19, but
the absolute numbers of deaths (n ¼ 16) and ICU admissions (n ¼ 68)
informing these comparisons were small. When pregnant women with
COVID-19 were compared to non-pregnant women of reproductive
age with COVID-19, the risk of mortality was similar (0.3% vs.
0.6%), but the risks of ICU admission, invasive ventilation, and
need for extracorporeal membrane oxygenation (ECMO) were
increased. Of the 192 studies included in the review, none was from
a low-income country and 9 were from lower middle-income coun-
tries. A multinational study involving 18 countries including 4 low-
middle income countries compared pregnancy outcomes between
COVID-infected and non-infected pregnant individuals during the
period March to October 2020.6 COVID-19 infection was associated
with a substantial increase in severe maternal morbidity and maternal
mortality, and neonatal complications.
With subsequent waves of COVID-19, several centers have
reported increasing numbers of critically ill pregnant women with
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COVID-19 compared with the first wave. The Royal Brompton
Hospital in London, an ECMO referral center, reports the referral
of 4 peripartum women (out of 34 referrals for women aged 16–
49 years, 12%) for potential ECMO in the first wave (1 March–31
August 2020) and 19 (31% of 62 referrals) in the second wave (1
September 2020–4 March 2021).7 The Intensive Care National
Audit & Research Centre (ICNARC) reports similar findings
across the U.K., with the number of peripartum women requiring
admission to intensive care increasing from 70 (8.9% of all women
aged 16–49 years) in the first wave to 270 (13.5%) in the second
wave.8 Brazil has reported a disproportionately large number of
maternal deaths attributed to COVID-19, with an in-hospital mor-
tality rate of 8.3%, with a marked predominance in Black women.9
Furthermore, reported maternal deaths due to severe acute respira-
tory illness in Brazil in 2020 were 1.5 times greater than that reported
in 2016, likely due to COVID-19 deaths. A study from Spain dem-
onstrates a marked increase in pregnant and postpartum women
admitted to hospital in the second wave compared with the first,
although no mortality was documented.10 A UKOSS report com-
pared symptomatic pregnant women admitted to hospital with con-
firmed COVID-19 during the initial (March to November 2020) and
later (December 2020 to February 2021) waves.11 Women admitted
during the later wave when the B.1.1.7 variant became predominant
were more likely to require critical care (OR 1.62) and respiratory
support (OR 2.58). Our experience in the ICU at Mount Sinai
Hospital, Toronto, a large referral obstetric unit, is very similar: 5
pregnant women with COVID-19 were admitted between March
2020 and January 2021, increasing to 14 women between March
and May 2021, corresponding with the third wave in Canada which
was predominated by the B.1.1.7 (Alpha) VOC. The largest study of
African patients, critically ill patients with COVID-19, enrolled 3140
patients and found a 48.2% risk of hospital mortality (to 30 days),
which was 11%–23% higher than the non-African global risk.12 This
study did not report data on pregnant women but given that the
excess mortality was likely driven in part by limited resources, out-
comes from pregnant women would be expected to be similar.
Could this dramatic apparent increase in the risk of critical illness
with COVID-19 in subsequent waves of infection be related to
increased pathogenicity of the VOCs in the pregnant woman, or is
it simply a reflection of increased total number of COVID infections
in younger individuals? Currently, there are no data to answer this
question. The consistent difference between the first and later waves
seems to suggest a change in pathogenicity in pregnant women, but
this requires further study. What is evident, however, is that COVID-
19 is not the benign disease in pregnancy that initial experience led us
to hope. Although in some high-income countries, successful vacci-
nation programs have dramatically reduced the burden of COVID-19
infection, in most of the world the pandemic continues as a major
public health crisis. Pregnant women are now recognized as a high-
risk subgroup and are at significant risk in areas least able to provide
high-level supportive care. Limited data suggest that vaccination in
pregnancy is safe,13 and this vulnerable group needs to be a priority
in global vaccination programs.
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Contributorship
Both authors contributed to writing this manuscript.
ORCID iDs
Stephen E Lapinsky https://orcid.org/0000-0002-6930-0306
Neill KJ Adhikari https://orcid.org/0000-0003-4038-5382
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Stephen E Lapinsky
Sinai Health System, University of Toronto, Toronto,
Ontario, Canada
Email: Stephen.lapinsky@utoronto.ca
Neill KJ Adhikari
Sunnybrook Health Sciences Centre, University of
Toronto, Toronto, Ontario, Canada