A Mumbai woman in her late 20s has become the first to suffer a miscarriage due to Covid-19 in India. There are not many known Covid-19-related complications in pregnancy, and there is limited research on how the novel coronavirus affects the unborn child.
Some early studies by ICMR-National Institute for Research in Reproductive Health (NIRRH) found that the placenta, supposed to protect the foetus from infections, in fact acts as a reservoir for SARS-CoV-2.
What happened in this case in Mumbai?
On August 22, medRxiv, the preprint server for health sciences research, published a paper on a woman in her late 20s whose foetus had died in the uterus. The woman, a security guard in a government hospital in Mumbai, was in her first trimester.
The woman had contact with a Covid-19 positive case when she was eight weeks pregnant. She had no symptoms, but a precautionary nasopharyngeal test returned positive for the virus, and she was admitted to institutional isolation.
About four weeks later, a second test showed no trace of the virus in her nasopharyngeal tract. She was healthy, but a week later (when she was 13 weeks pregnant), a routine ultrasound test found that the foetus had died.
“We were curious and decided to run more tests,” Dr Prajakta Shende of the gynaecology department of ESIS hospital, said.
What did the tests show?
The unborn baby suffered from a condition called ‘hydrops fetalis’, which is the abnormal accumulation of fluid in the body. It was suspected to have been caused by inflammation.
Dr Deepak Modi, placenta biologist at NIRRH, said the pregnant woman had tested negative for Covid-19 in a repeat test, which meant the virus had cleared from her throat and nasal tract, but the infection may have travelled towards the womb.
The placenta, amniotic fluid from the gestational sac, and the foetal membrane were tested – and the placenta and amniotic fluid showed active SARS-CoV-2 virus replication. This was surprising because it had been over five weeks since the woman was infected.
Doctors concluded that placental infection due to Covid-19 had led to inflammation and the death of the foetus.
Has there been a similar case elsewhere?
A similar case of miscarriage was recorded in a 28-year-old woman in Switzerland in March. The woman, who was obese and infected with the virus, gave birth to a stillborn child in the second trimester.
It is not clear why the coronavirus infects the placenta in some cases, and does not in other pregnancies.
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What role does the placenta play in the infection?
The placenta acts as a barrier that protects the foetus in the uterus from external infections. But some studies have suggested it may in fact act as a reservoir for the coronavirus, allowing it to replicate.
At least 17 studies covering 93 Covid-19 infected pregnant women have been carried out to analyse the virus in placental tissue, and the placenta has tested positive in 12 per cent of cases. (‘Single Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors Driving Pathogenesis of SARS-CoV-2’, ‘Frontiers in Cell and Developmental Biology‘, August 19, 2020).
The researchers, from ICMR-NIRRH and BSSE, IISc, found the placenta has an abundance of ‘S protein proteases’ and ‘ACE2’ receptors during the first, second, and third trimesters, both of which act as an entry point in the cell for SARS-Cov-2.
“We used single-cell RNA-seq data in placenta. Placental cells also have machinery that helps in replication of the virus. We are still not sure why vertical transmission happens but placenta may act as an entry point for the virus,” said Dr Smita Mahale, Director, NIRRH.
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How common is vertical transmission in pregnant Covid-19 infected women?
Although not very common, vertical transmission has been noted worldwide. The US Centres for Disease Control and Prevention (CDC) has observed that Covid-19 infected pregnant women are at greater risk of needing hospitalisation and intensive care. The CDC has records of 18,040 pregnant women until August 18 – of which 4,472 required hospitalisation, and 39 Covid-19 infected pregnant women died.
No similar data are available in India. Anecdotally, treating doctors report that most Covid-19 infected women are asymptomatic or mildly symptomatic. In Mumbai’s Nair hospital, which has tracked deliveries in 400 infected women, four women died due to other medical conditions, and none recorded vertical transmission. In Wadia hospital, three cases of vertical transmission were recorded among the over 200 deliveries.
“Limited reports in the literature have raised concern of possible intrauterine, intrapartum, or peripartum transmission,” the CDC states. If newborns do get infected, most have mild or no symptoms, and they recover quickly. Another way in which newborns can be infected is through respiratory droplets from an infected mother.
Is anything being done to understand vertical transmission better in India
To understand placental infection in Covid-19 better, Wadia hospital along with NIRRH will conduct tests on 100 pregnant women to check whether their placenta has coronavirus after delivery.
ICMR-NIRRH has tied up with the Maharashtra government and 19 medical colleges to create a registry of Covid-19 infected pregnant women, and of their post-partum period. This is the first such registry in India. Until August 20, over 1,000 women had been registered.
Fifty-four investigators attached to the registry will study how the coronavirus affects pregnancy, newborns, women in the post-partum period of 42 days after delivery, and the outcome of the infection in mother and child. The registry will help frame policy on maternal child care during the pandemic, those who are involved in monitoring the exercise said.