key: cord-1007478-hkq0j7o9 authors: Engjom, H. M.; Ramakrishnan, R.; Vousden, N.; Bunch, K.; Morris, E. P.; Simpson, N.; Gale, C.; OBrien, P.; Quigley, M.; Brocklehurst, P.; Kurinczuk, J. J.; Knight, M. title: Severity of maternal SARS-CoV-2 infection and perinatal outcomes during the Omicron variant dominant period: UK Obstetric Surveillance System national cohort study. date: 2022-03-09 journal: nan DOI: 10.1101/2022.03.07.22271699 sha: 79e179cf9a8088acc6be728ca99122956a959133 doc_id: 1007478 cord_uid: hkq0j7o9 Objectives To describe the severity of maternal infection when the Omicron SARS-CoV-2 variant was dominant (15/12/21-14/01/22) and compare outcomes among groups with different vaccination status. Design: Prospective cohort study Setting: UK consultant-led maternity units Participants: Pregnant women hospitalised with a positive SARS-CoV-2 PCR test up to 7 days prior to admission and/or during admission up to 2 days after giving birth. Main outcome measures: Symptomatic or asymptomatic infection. Vaccination status. Severity of maternal infection (moderate or severe infection according to modified WHO criteria). Mode of birth and perinatal outcomes. Results: Out of 1561 women admitted to hospital with SARS-CoV-2 infection, 449 (28.8%) were symptomatic. Among symptomatic women admitted, 86 (19.2%) had moderate to severe infection; 51 (11.4%) had pneumonia on imaging, 62 (14.3%) received respiratory support, and 19 (4.2%) were admitted to the intensive care unit (ICU). Three women died (0.7%). Vaccination status was known for 383 symptomatic women (85.3%) women; 249 (65.0%) were unvaccinated, 45 (11.7%) had received one vaccine dose, 76 (19.8%) had received two doses and 13 (3.4%) had received three doses. 59/249 (23.7%) unvaccinated women had moderate to severe infection, compared to 10/45 (22.2%) who had one dose, 9/76 (11.8%) who had two doses and 0/13 (0%) who had three doses. Among the 19 symptomatic women admitted to ICU, 14 (73.7%) were unvaccinated, 3 (15.8%) had received one dose, 1 (5.3%) had received two doses, 0 (0%) had received 3 doses and 1 (5.3%) had unknown vaccination status. Conclusion The risk of severe respiratory disease amongst unvaccinated pregnant women admitted with symptomatic SARS-CoV-2 infection during the omicron dominance period was comparable to that observed during the period the wildtype variant was dominant. Most women with severe disease were unvaccinated. Vaccine coverage among pregnant women admitted with SARS-CoV-2 was low compared to the overall pregnancy population and very low compared to the general population. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential. • In non-pregnant adults, growing evidence indicates a lower risk of severe respiratory disease with the Omicron SARS-CoV-2 Variant of Concern (VOC) . • Pregnant women admitted during the periods in which the Alpha and Delta VOC were dominant were at increased risk of moderate to severe SARS-CoV-2 infection compared to the period when the original wildtype infection was dominant. • Most women admitted to hospital with symptomatic SARS-CoV-2 infection have been unvaccinated. • One in four women who had received no vaccine or a single dose had moderate to severe infection, compared with one in eight women who had received two doses and no women who had received three doses • The proportional rate of moderate to severe infection in unvaccinated pregnant women during the Omicron dominance period is similar to the rate observed during the wildtype dominance period • One in eight symptomatic admitted pregnant women needed respiratory support during the period when Omicron was dominant . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; In 2020 the World Health Organization's (WHO) living systematic review concluded that 79 SARS-CoV-2 infection during pregnancy was associated with an increased risk of admission 80 to intensive care (ICU) for the mother, increased risk of preterm birth and admission for 81 neonatal care for the infant. 1 VOC, severe maternal infection was more frequent compared to the wildtype period, and 89 perinatal outcomes were worse 3-5 . The majority of severe maternal and perinatal outcomes 90 occurred among unvaccinated women during periods with alpha and delta as dominant 91 variants. 6 7 8 Initial studies of Omicron infection in non-pregnant populations indicate a lower 92 risk of severe pulmonary disease with this variant compared to the previous delta VOC. 9 There is an urgent need for robust national data to inform women who are pregnant or plan a 97 pregnancy, as well as health professionals providing care for pregnant women, and policy 98 makers. The primary aim of this study was therefore to describe the characteristics of 99 pregnant women admitted to hospital with SARS-CoV-2 infection including vaccination 100 status, severity of infection, pharmacologic management, pregnancy, and perinatal 101 outcomes, in the first period when the Omicron VOC was dominant in the UK. 102 103 METHODS 104 105 Design, data sources and study period 106 A national, prospective observational cohort study was conducted using the UK Obstetric 107 Surveillance System (UKOSS). 12 This system entails active surveillance with reporting from 108 all 194 hospitals in the UK with a consultant-led maternity unit, and includes well established 109 routines to secure complete reporting. 13 Information on women who died, or who had 110 stillbirths or neonatal deaths, was cross-checked with data from the organisation responsible 111 for maternal and perinatal death surveillance in the UK (MBRRACE-UK). 14 As individual-112 level SARS-CoV-2 variant data were not recorded in medical records, the data collection 113 time period was restricted to the period in which the Omicron SARS-CoV-2 variant was the 114 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Women were included if they were admitted to hospital during pregnancy and had a positive 120 SARS-CoV-2 PCR test at the time of admission. Hospital admission was defined as an 121 overnight or longer hospital admission for any cause, or admission of any duration to give 122 birth. Women not meeting this case definition were excluded ( Figure 1 ). The included 123 women were categorised in two mutually exclusive groups based on covid-19 symptoms. 124 Symptomatic group: women who were admitted due to covid-19 or who were reported to be 125 symptomatic or who received respiratory support of any kind. 126 Asymptomatic group: women admitted for labour, obstetric care or other reasons and who 127 were not reported to have SARS-CoV-2-related symptoms and who did not receive 128 respiratory support, or who were reported to be asymptomatic if the reason for admission 129 was not known. 130 The following sociodemographic and medical risk factors were included: maternal age, body 149 mass index (BMI) in kg/m 2 , occupation (woman or partner in paid work vs neither in paid 150 work), minority ethnic background (Asian, Black, Chinese, other or mixed ethnic minorities vs 151 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 9, 2022. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The characteristics of included women stratified by admission group are shown in Table 1 . (Table 2) . However, the proportion of 207 symptomatic women who received any specific pharmacological therapy was low (n=31, 208 6.9%); 0.4% (n=2) received antivirals, 1.6% (n=7) received tocilizumab, 5.8% (n=26) 209 received corticosteroids for maternal indication, and 0.9% (n=4) received monoclonal 210 antibodies. Four women were recruited to the RECOVERY trial. Among the 19 symptomatic 211 women admitted to ICU, 10 (52.6%) received a specific pharmacological therapy, 1 woman 212 (5.3%) received antivirals, 4 (21.0%) received tocilizumab, 9 (47.4%) received 213 corticosteroids for a maternal indication and 2 (10.5%) received monoclonal antibodies. 214 215 The proportion of symptomatic women who had received none, one, two or three vaccine 217 doses was 65.1% (n=249), 11.8% (n=45), 19.8% (n=76), and 3.4% (n=13), respectively 218 (Table 1) . A total of 78 (20.4%) symptomatic women whose vaccination status was known 219 had a composite measure of moderate to severe infection. More than a fifth of unvaccinated 220 women (59/249, 23.7%) and women who had received one dose (10/45, 22.2%) had 221 moderate to severe infection, compared to one in ten (9/76, 11.8%) who had two doses and 222 none (0/13, 0%) who had three doses. Forty of the women in the two-dose group (52.6%) 223 were known to have received their second vaccine dose more than three months prior to 224 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. One thousand, one hundred and seventy-two women had completed their pregnancies, 240 232 (53.5%) of the women in the symptomatic group and 932 (83.8%) in the asymptomatic group 233 (Table 4 ). Almost a third of symptomatic women (n=144, 32.1%) were known to have been 234 discharged still pregnant. The proportion of births at gestational weeks 22 to 36 was 17.8% 235 (n=42) amongst symptomatic women versus 10.7% (n=96) in asymptomatic women. Birth 236 expedited due to covid-19 was reported for 7.6% (n=18) in the symptomatic group; none of 237 these women were known to have received three vaccine doses (Table 5) . 238 239 Among 1159 infants, 10 stillbirths were reported; in the symptomatic and asymptomatic 240 groups stillbirths occurred in 0.8% (n=2) and 0.9% (n=8) of total births, respectively (Table 241 6). Eight of the ten stillbirths occurred to women who were unvaccinated or had one vaccine 242 dose, but the role of SARS-CoV-2 in the stillbirth needs to be assessed in formal audit. 243 Admission to a neonatal unit was reported for 15.4% (n=37) of infants born to symptomatic 244 women and 8.5% (n=78) of infants born to asymptomatic women. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; https://doi.org/10.1101/2022.03.07.22271699 doi: medRxiv preprint To our knowledge, this is the first national prospective cohort study to describe pregnancy 264 and perinatal outcomes during the period when the Omicron SARS-CoV-2 variant was 265 dominant. A key strength of these data is the existing mechanism for national case 266 identification of all women admitted to hospital across the UK, and therefore the low risk of 267 selection bias. In the UK, universal SARS-CoV-2 testing for all obstetric admissions was 268 implemented from May 2020. Asymptomatic pregnant women in whom SARS-CoV-2 269 infection is detected by screening on admission, are most commonly admitted to give birth. 17 270 We therefore categorised the included women by cause of admission or symptoms to avoid 271 misclassification bias and increased adverse outcomes being incorrectly attributed to SARS-272 CoV-2. 18 CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. Covid-19-specific pharmacological therapies, which are now standard care for non-pregnant 299 patients, were used infrequently, even for women that needed respiratory support. The 300 proportion that received any pharmacological treatment for covid-19 (one or more of an 301 antiviral, tocilizumab, maternal corticosteroids and monoclonal antibodies) was lower than in 302 the Alpha and Delta periods, 6.9% vs 14.9% and 13.6% respectively. While this may partly 303 reflect a lower severity of illness, it is concerning that only around half of pregnant women 304 admitted to ICU due to covid-19 received any covid-19 specific pharmacological treatment. 305 The RCOG recommended in June 2020 that corticosteroid therapy should be considered for 306 all women who were clinically deteriorating due to covid-19. 16 Maternal corticosteroid 307 treatment was reported for 5.8% of symptomatic women during the Omicron period, 308 compared to 12.7% and 12.0% during the Alpha and Delta periods, respectively. In the 309 current study 47% of women admitted to intensive care received corticosteroids. In the general adult population, effectiveness after the second dose declines from 60-75% 328 three weeks after vaccination to 20% at 15 weeks and 10% after 25 weeks, 20 and three 329 doses have been shown to give better protection against severe disease with the Omicron 330 VOC in adults. 21 The interval between the last dose and the admission was 3 months or 331 more among half (53%) of the women who had received two doses of vaccine. The number 332 of pregnant women who had received a third booster dose was low in our study, but no 333 severe cases in this group indicates the importance of the third dose to protect pregnant 334 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. backgrounds were less prominent in the current study than previously described during the 339 wildtype period. 13 National guidance has emphasised the importance of addressing this 340 inequality and advised active health seeking in these groups. 16 The observation time in the 341 current study is short and the findings cannot yet reliably indicate if the smaller differences 342 can be attributed to better communication, prevention, health care seeking strategies or 343 previous infection. Preliminary surveillance results indicated that the Omicron VOC has a 344 secondary attack rate of 10-13% and therefore factors that increase transmission, such as 345 multi-occupancy housing and public-facing occupations, are important also for this variant. 22-346 24 Since socioeconomic deprivation is also a known independent risk factor for adverse 347 pregnancy outcome, this could be a source of residual confounding in this study. preventable, yet vaccine uptake among pregnant women remains low compared to the 367 general female population in fertile age. Continued, strong efforts to improve uptake of the 368 vaccine during pregnancy are still needed. This is of even greater importance as infection 369 continues to rapidly rise in both high and low-resourced settings. 27 370 371 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; 372 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. Steering Committee without whose support this research would not have been possible. 394 395 All authors contributed to conceptualisation, the writing and editing of this study, had final 397 approval of the version to be published and agree to be accountable for all aspects of the 398 work. KB, EM, NS, CG, PO, MQ, PB, JK and MK contributed to funding acquisition, 399 supervision, and methodology. HE, RR, NV, KB and MK contributed to data curation and 400 formal analysis, and had access to verify the underlying data. MK, as guarantor, accepts full 401 responsibility for the work and affirms that the manuscript is an honest, accurate and 402 transparent account of the study being reported; that no important aspects of the study have 403 been omitted; and that any discrepancies from the study as originally planned have been 404 explained. The corresponding author attests that all listed authors meet authorship criteria 405 and that no others meeting the criteria have been omitted. 406 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; The Corresponding Author has the right to grant on behalf of all authors and does grant on 407 behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in 408 all forms, formats and media (whether known now or created in the future), to i) publish, 409 reproduce, distribute, display and store the Contribution, ii) translate the Contribution into 410 other languages, create adaptations, reprints, include within collections and create 411 summaries, extracts and/or, abstracts of the Contribution, iii) create any other derivative 412 work(s) based on the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) 413 the inclusion of electronic links from the Contribution to third party material where-ever it may 414 be located; and, vi) licence any third party to do any or all of the above. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; https://doi.org/10.1101/2022.03.07.22271699 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; https://doi.org/10.1101/2022.03.07.22271699 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. ; is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 9, 2022. 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