Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

BMJ 2020370 doi: https://doi.org/10.1136/bmj.m3320 (Published 01 September 2020)
Cite this as: BMJ 2020;370:m3320

  1. John Allotey, senior research fellow in epidemiology and women’s health12,
  2. Elena Stallings, researcher34,
  3. Mercedes Bonet, medical officer5,
  4. Magnus Yap, medical student6,
  5. Shaunak Chatterjee, medical student6,
  6. Tania Kew, medical student6,
  7. Luke Debenham, medical student6,
  8. Anna Clavé Llavall, medical student6,
  9. Anushka Dixit, medical student6,
  10. Dengyi Zhou, medical student6,
  11. Rishab Balaji, medical student6,
  12. Siang Ing Lee, researcher1,
  13. Xiu Qiu, chief consultant of women’s health789,
  14. Mingyang Yuan, researcher17,
  15. Dyuti Coomar, research fellow1,
  16. Madelon van Wely, clinical epidemiologist10,
  17. Elizabeth van Leeuwen, medical specialist11,
  18. Elena Kostova, managing editor10,
  19. Heinke Kunst, senior lecturer and consultant in respiratory medicine1213,
  20. Asma Khalil, professor of obstetrics and maternal-fetal medicine14,
  21. Simon Tiberi, infectious disease consultant1213,
  22. Vanessa Brizuela, doctor of public health5,
  23. Nathalie Broutet, medical officer5,
  24. Edna Kara, public health specialist3,
  25. Caron Rahn Kim, medical officer5,
  26. Anna Thorson, professor in global infectious disease epidemiology5,
  27. Olufemi T Oladapo, acting head of maternal and perinatal health unit5,
  28. Lynne Mofenson, paediatric infectious disease specialist15,
  29. Javier Zamora, senior lecturer in biostatistics3416,
  30. Shakila Thangaratinam, professor of maternal and perinatal health217,
  31. for PregCOV-19 Living Systematic Review Consortium

Author affiliations

  1. Correspondence to: S Thangaratinam s.thangaratinam.1@bham.ac.uk (or @thangaratinam on Twitter)
  • Accepted 23 August 2020

Abstract

Objective To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).

Design Living systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists.

Study selection Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.

Data extraction At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.

Results 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19.

Conclusion Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease.

Systematic review registration PROSPERO CRD42020178076.

Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Mulheres em combate: 6 líderes brasileiras na linha de frente da crise de Covid-19

Weerayut Ranmai/Cavan Images/GettyImages

Mulheres representam 65% dos seis milhões de profissionais da área da saúde no Brasil

Na semana em que o número de casos de Covid-19 no Brasil chegou a 3 milhões e o de mortes atingiu a marca histórica de 100 mil, mais do que nunca os desafios impostos pelo novo coronavírus requerem atenção. Além das iniciativas de assistência social e econômica, a pandemia demanda ações rápidas, efetivas e antecipadas na área da saúde –marcada pela prevalência dos rostos de mulheres.

Segundo o relatório “Covid-19: Um Olhar para Gênero” do Fundo de População das Nações Unidas (da sigla em inglês UNFPA), 70% da força de trabalho ligada à área da saúde no mundo é feminina. No Brasil, os números são parecidos. O Conselho Nacional de Secretarias Municipais de Saúde (Conasems), indica que 65% dos seis milhões de profissionais do setor são do sexo feminino –em áreas como fonoaudiologia, nutrição e serviço social elas ultrapassar 90% de presença, e 80% em enfermagem e psicologia.

(…) leia o artigo completo no site da Forbes.

Why Does the Coronavirus Hit Men Harder? A New Clue

Women produce a more powerful immune response than do men, a new study finds.

Do NewYork Times

In a hospital in La Mesa, Calif., earlier this year, a nurse held a phone to the ear of a patient with coronavirus so he could listen to his daughter speak. 
In a hospital in La Mesa, Calif., earlier this year, a nurse held a phone to the ear of a patient with coronavirus so he could listen to his daughter speak. Credit…Etienne Laurent/EPA, via Shutterstock

The coronavirus may infect anyone, young or old, but older men are up to twice as likely to become severely sick and to die as women of the same age.

Why? The first study to look at immune response to the coronavirus by sex has turned up a clue: Men produce a weaker immune response to the virus than do women, the researchers concluded.

The findings, published on Wednesday in Nature, suggest that men, particularly those over age 60, may need to depend more on vaccines to protect against the infection.

“Natural infection is clearly failing” to spark adequate immune responses in men, said Akiko Iwasaki, an immunologist at Yale University who led the work.

The results are consistent with what’s known about sex differences following various challenges to the immune system.

Women mount faster and stronger immune responses, perhaps because their bodies are rigged to fight pathogens that threaten unborn or newborn children.

But over time, an immune system in a constant state of high alert can be harmful. Most autoimmune diseases — characterized by an overly strong immune response — are much more prevalent in women than in men, for example.

“We are looking at two sides of the same coin,” said Dr. Marcus Altfeld, an immunologist at the Heinrich Pette Institute and at the University Medical Center Hamburg-Eppendorf in Germany.

The findings underscore the need for companies pursing coronavirus vaccines to parse their data by sex and may influence decisions about dosing, Dr. Altfeld and other experts said.

“You could imagine scenarios where a single shot of a vaccine might be sufficient in young individuals or maybe young women, while older men might need to have three shots of vaccine,” Dr. Altfeld said.

Companies pursuing coronavirus vaccines have not yet released clinical data analyzed by the participants’ sex, but the Food and Drug Administration has asked them to do so, as well as by racial and ethnic background, said Dr. William Gruber, a vice president at Pfizer.

Dr. Iwasaki’s team analyzed immune responses in 17 men and 22 women who were admitted to the hospital soon after they were infected with the coronavirus. The researchers collected blood, nasopharyngeal swabs, saliva, urine and stool from the patients every three to seven days.

The analysis excluded patients on ventilators and those taking drugs that affect the immune system “to make sure that we’re measuring natural immune response to the virus,” Dr. Iwasaki said.

The researchers also analyzed data from an additional 59 men and women who did not meet those criteria.

Over all, the scientists found, the women’s bodies produced more so-called T cells, which can kill virus-infected cells and stop the infection from spreading.

Men showed much weaker activation of T cells, and that lag was linked to how sick the men became. The older the men, the weaker their T cell responses.

“When they age, they lose their ability to stimulate T cells,” Dr. Iwasaki said. “If you look at the ones that really failed to make T cells, they were the ones who did worse with disease.”

But “women who are older — even very old, like 90 years old — these women are still making pretty good, decent immune response,” she added.

Compared with health care workers and healthy controls, the patients all had elevated blood levels of cytokines, proteins that rouse the immune system to action. Some types of cytokines, called interleukin-8 and interleukin-18, were elevated in all men but only in some women.

Women who had high levels of other cytokines became more seriously ill, the researchers found. Those women might do better if given drugs that blunt these proteins, Dr. Iwasaki said.

The study has limitations. It was small, and the patients were older than 60 on average, making it difficult to assess how the immune response changes with age.

“We know that age is proving to be a very important factor in Covid-19 outcomes, and the intersection of age and sex must be explored,” said Sabra Klein, a vaccine expert at the Johns Hopkins Bloomberg School of Public Health.

The study also did not offer a reason for the differences between men and women. Because the women were past menopause, on average, “it is doubtful that sex steroid hormones are involved,” Dr. Klein said.

Still, the new findings are “exciting” because they begin to explain why men fare so much worse with the coronavirus, she added: “The more robust T cell responses in older women could be an important clue to protection and must be explored further.”