Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study

Background

In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern.

Methods

INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile.

Findings

We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0–38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03–1·31]) and SPMMI (RR 1·21 [95% CI 1·00–1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88–1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12–1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84–3·43]), perinatal complications (RR 1·84 [95% CI 1·02–3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67–20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02–4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44–41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22–65) and 76% (47–89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose.

Interpretation

COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority.

Author list

 

Affiliations:

  1. Nuffield Department of Women’s & Reproductive Health and Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK
  2. Division Neonatología, Hospital Materno Infantil Ramón Sarda, Buenos Aires, Argentina 
  3. Center for Environmental Research and Community Health (CERCH), School of Public Health, University of California, Berkeley, CA, USA
  4. Department of Paediatrics and Child Health, The Aga Khan University Hospital, Karachi, Pakistan 
  5. Vita- Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Obstetrics and Gynaecology Department, Milan, Italy 
  6. Department of Clinical Sciences and Community Health, University of Milan, NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy 
  7. Unit of Obstetrics and Gynecology, L- Sacco Hospital ASST Fatebenefratelli Sacco, Department of Biological and Clinical Sciences, University of Milan, Milan, Italy 
  8. Department of Obstetrics and Gynecology, Sancaktepe Sehit Prof Dr Ilhan Varank Training and Research Hospital, University of Health Sciences, Istanbul, Türkiye 
  9. Neonatal Care Unit, Department of Public Health and Pediatrics, School of Medicine, University of Turin, Turin, Italy
  10. Instituto de Investigación Sanitario de Aragón (IIS Aragon), Hospital Clínico Universitario Lozano Blesa Zaragoza, Zaragoza, Spain
  11. Department of Pediatrics, Gynecology & Obstetrics, Hôpitaux Universitaires de Genève, Geneva, Switzerland
  12. Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico 
  13. Children's Hospital V Buzzi, ASST Fatebenefratelli Sacco, Milan, Italy
  14. Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, UK
  15. Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK
  16. Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Vall d’Hebron, Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Barcelona, Spain
  17. Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
  18. Tufts Medical Center, Boston, MA, USA 
  19. Department of Obstetrics and Gynecology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France 
  20. Servicio de Neonatologia, Hospital Italiano de Buenos Aires, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina 
  21. Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA 
  22. Maternal and Child Department, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
  23. Hôpital Universitaire Necker-Enfants Malades, Paris, France
  24. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
  25. Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
  26. Department of Obstetrics and Gynecology and Department of Global Health, University of Washington, Seattle, WA, USA 
  27. Hospital Universitário da Universidade Federal do Maranhão, São Luís, Maranhão, Brazil
  28. Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
  29. Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France
  30. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  31. Servicio de Neonatología del Departamento Materno Infantil, Hospital Universitario Austral, Buenos Aires, Argentina
  32. St George’s University Hospitals NHS Foundation Trust, London, UK
  33. Hospital Julio C Perrando, Resistencia, Chaco, Argentina 
  34. Clínica y Maternidad Suizo Argentina, Buenos Aires, Argentina
  35. Medical Faculty Universitas Airlangga - Dr Soetomo General Academic Hospital, Surabaya, Indonesia
  36. Obstetrics and Gynecology Division- Hadassah Medical Center Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  37. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
  38. Sanatorio Otamendi, Buenos Aires, Argentina
  39. Ascension– Resurrection Medical Center, Chicago, Illinois, USA
  40. Departmentof Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
  41. General Hospital With Extended Activity Prilep, Prilep, North Macedonia
  42. Department of Obstetrics and Gynaecology, College of Medical Sciences, Gombe State University, Gombe, Nigeria
  43. College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
  44. University of Nottingham Medical School, University of Nottingham, Nottingham, UK
  45. Center for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada

Authors:

Jose Villar, Constanza P Soto Conti, Robert B Gunier, Shabina Ariff, Rachel Craik, Paolo I Cavoretto, Stephen Rauch, Serena Gandino, Ricardo Nieto, Adele Winsey, Camilla Menis, Gabriel B Rodriguez, Valeria Savasi, Niyazi Tug, Sonia Deantoni, Marta Fabre, Begoña Martinez de Tejada, Maria Jose Rodriguez-Sibaja, Stefania Livio, Raffaele Napolitano, Nerea Maiz, Helena Sobrero, Ashley Peterson, Philippe Deruelle, Carolina Giudice, Jagjit S Teji, Roberto A Casale, Laurent J Salomon, Federico Prefumo, Leila Cheikh Ismail, Michael G Gravett, Marynéa Vale, Valeria Hernández, Loïc Sentilhes, Sarah R Easter, Carola Capelli, Emily Marler, Daniela M Cáceres, Guadalupe Albornoz Crespo, Ernawati Ernawati, Michal Lipschuetz, Ken Takahashi, Carmen Vecchiarelli, Teresa Hubka, Satoru Ikenoue, Gabriela Tavchioska, Babagana Bako, Adejumoke I Ayede, Brenda Eskenazi, Jim G Thornton, Zulfiqar A Bhutta, Stephen H Kennedy*, Aris T Papageorghiou*, for the INTERCOVID-2022 International Consortium

Novel Coronavirus SARS-CoV-2

10.1016/S0140-6736(22)02467-9

The Lancet

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