Quality of life 1 year after hospital discharge in unvaccinated pregnant women with COVID-19 respiratory symptoms: a prospective observational study (ODISSEA-PINK study)

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.

Studies suggest that pregnant women might be at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) ( 1 , 2 ). This report provides updated information about symptomatic women of reproductive age (15–44 years) with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19. During January 22–October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15–44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant. After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6–3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2–3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5–4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2–2.4). Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19–associated illness. To reduce the risk for severe illness and death from COVID-19, pregnant women should be counseled about the importance of seeking prompt medical care if they have symptoms and measures to prevent SARS-CoV-2 infection should be strongly emphasized for pregnant women and their families during all medical encounters, including prenatal care visits. Understanding COVID-19–associated risks among pregnant women is important for prevention counseling and clinical care and treatment. Data on laboratory-confirmed and probable COVID-19 cases † were electronically reported to CDC using a standardized case report form § or NNDSS ¶ as part of COVID-19 surveillance efforts. Data are reported by health departments and can be updated by health departments as new information becomes available. This analysis included cases initially reported to CDC during January 22–October 3, 2020, with data updated as of October 28, 2020. Cases were limited to those in symptomatic women aged 15–44 years in the United States with laboratory-confirmed infection (detection of SARS-CoV-2 RNA in a clinical specimen using a molecular amplification detection test). Information on demographic characteristics, pregnancy status, underlying medical conditions, symptoms, and outcomes was collected. Pregnancy status was ascertained by a pregnancy field on the COVID-19 case report form or through records linked to the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) optional COVID-19 module** , †† ( 3 ). CDC ascertained symptom status either through a reported symptom status variable (symptomatic, asymptomatic, or unknown) or based on the presence of at least one specific symptom on the case report form. Outcomes with missing data were assumed not to have occurred. Crude and adjusted RRs and 95% CIs were calculated using modified Poisson regression. Overall and stratified risk ratios were adjusted for age (in years), race/ethnicity, and presence of diabetes, cardiovascular disease (including hypertension), and chronic lung disease. SAS (version 9.4; SAS Institute) was used to conduct all analyses. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. §§ During January 22–October 3, a total of 5,003,041 laboratory-confirmed cases of SARS-CoV-2 infection were reported to CDC as part of national COVID-19 case surveillance, including 1,300,938 (26.0%) cases in women aged 15–44 years. Data on pregnancy status were available for 461,825 (35.5%) women aged 15–44 years, 30,415 (6.6%) of whom were pregnant and 431,410 (93.4%) of whom were nonpregnant. Among all women aged 15–44 years with known pregnancy status, 409,462 (88.7%) were symptomatic, including 23,434 pregnant women, accounting for 5.7% of all symptomatic women with laboratory-confirmed COVID-19, and 386,028 nonpregnant women. Pregnant women were more frequently Hispanic/Latina (Hispanic) (29.7%) and less frequently non-Hispanic White (White) (23.5%) compared with nonpregnant women (22.6% Hispanic and 31.7% White). Among all women, cough, headache, muscle aches, and fever were the most frequently reported signs and symptoms; most symptoms were reported less frequently by pregnant women than by nonpregnant women (Table 1). TABLE 1 Demographic characteristics, signs and symptoms, and underlying medical conditions among symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection (N = 409,462),* ,† by pregnancy status — United States, January 22–October 3, 2020 Characteristic No. (%) of symptomatic women Pregnant (n = 23,434) Nonpregnant (n = 386,028) Total (N = 409,462) Age group, yrs 15–24 6,463 (27.6) 133,032 (34.5) 139,495 (34.1) 25–34 12,951 (55.3) 131,835 (34.2) 144,786 (35.4) 35–44 4,020 (17.2) 121,161 (31.4) 125,181 (30.6) Race/Ethnicity § Hispanic or Latina, any race 6,962 (29.7) 85,618 (22.2) 92,580 (22.6) AI/AN, non-Hispanic 113 (0.5) 1,652 (0.4) 1,765 (0.4) Asian, non-Hispanic 560 (2.4) 8,605 (2.2) 9,165 (2.2) Black, non-Hispanic 3,387 (14.5) 54,185 (14.0) 57,572 (14.1) NHPI, non-Hispanic 119 (0.5) 1,526 (0.4) 1,645 (0.4) White, non-Hispanic 5,508 (23.5) 124,305 (32.2) 129,813 (31.7) Multiple or other race, non-Hispanic 726 (3.1) 12,341 (3.2) 13,067 (3.2) Signs and symptoms Known status of individual signs and symptoms¶ 10,404 174,198 184,602 Cough 5,230 (50.3) 89,422 (51.3) 94,652 (51.3) Fever** 3,328 (32.0) 68,536 (39.3) 71,864 (38.9) Muscle aches 3,818 (36.7) 78,725 (45.2) 82,543 (44.7) Chills 2,537 (24.4) 50,836 (29.2) 53,373 (28.9) Headache 4,447 (42.7) 95,713 (54.9) 100,160 (54.3) Shortness of breath 2,692 (25.9) 43,234 (24.8) 45,926 (24.9) Sore throat 2,955 (28.4) 60,218 (34.6) 63,173 (34.2) Diarrhea 1,479 (14.2) 38,165 (21.9) 39,644 (21.5) Nausea or vomiting 2,052 (19.7) 28,999 (16.6) 31,051 (16.8) Abdominal pain 870 (8.4) 16,123 (9.3) 16,993 (9.2) Runny nose 1,328 (12.8) 22,750 (13.1) 24,078 (13.0) New loss of taste or smell†† 2,234 (21.5) 43,256 (24.8) 45,490 (24.6) Fatigue 1,404 (13.5) 29,788 (17.1) 31,192 (16.9) Wheezing 172 (1.7) 3,743 (2.1) 3,915 (2.1) Chest pain 369 (3.5) 7,079 (4.1) 7,448 (4.0) Underlying medical conditions Known underlying medical condition status§§ 7,795 160,065 167,860 Diabetes mellitus 427 (5.5) 6,119 (3.8) 6,546 (3.9) Cardiovascular disease 304 (3.9) 7,703 (4.8) 8,007 (4.8) Chronic lung disease 506 (6.5) 9,185 (5.7) 9,691 (5.8) Chronic renal disease 18 (0.2) 680 (0.4) 698 (0.4) Chronic liver disease 17 (0.2) 350 (0.2) 367 (0.2) Immunocompromised condition 124 (1.6) 2,496 (1.6) 2,620 (1.6) Neurologic disorder, neurodevelopmental disorder, or intellectual disability 44 (0.6) 1,097 (0.7) 1,141 (0.7) Psychiatric disorder 62 (0.8) 1,139 (0.7) 1,201 (0.7) Autoimmune disorder 26 (0.3) 515 (0.3) 541 (0.3) Severe obesity¶¶ 174 (2.2) 1,810 (1.1) 1,984 (1.2) Abbreviations: AI/AN = American Indian or Alaska Native; NHPI = Native Hawaiian or Other Pacific Islander. * Women with known pregnancy status, representing 52% of 783,072 total cases among symptomatic women aged 15–44 years. † All statistical comparisons were significant at α 100.4°F [38°C] or subjective), cough, shortness of breath, wheezing, difficulty breathing, chills, rigors, myalgia, rhinorrhea, sore throat, chest pain, nausea or vomiting, abdominal pain, headache, fatigue, diarrhea (three or more loose stools in a 24-hour period), new olfactory or taste disorder, or other symptom not otherwise specified on the form. ** Patients were included if they had information for either measured or subjective fever variables and were considered to have a fever if “yes” was indicated for either variable. †† New olfactory and taste disorder has only been included on the CDC’s Human Infection with 2019 Novel Coronavirus Case Report Form since May 5, 2020. Therefore, data might be underreported for this symptom. §§ Status was classified as “known” if any of the following conditions were noted as present or absent on the CDC’s Human Infection with 2019 Novel Coronavirus Case Report Form: diabetes mellitus, cardiovascular disease (including hypertension), severe obesity (body mass index ≥40 kg/m2), chronic renal disease, chronic liver disease, chronic lung disease, immunosuppressive condition, autoimmune condition, neurologic condition (including neurodevelopmental, intellectual, physical, visual, or hearing impairment), psychological/psychiatric condition, and other underlying medical condition not otherwise specified. ¶¶ Defined as body mass index ≥40 kg/m2. Compared with nonpregnant women, pregnant women more frequently were admitted to an ICU (10.5 versus 3.9 per 1,000 cases; aRR = 3.0; 95% CI = 2.6–3.4), received invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2–3.8) and received ECMO (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5–4.0). Thirty-four deaths (1.5 per 1,000 cases) were reported among 23,434 symptomatic pregnant women, and 447 (1.2 per 1,000 cases) were reported among 386,028 nonpregnant women, reflecting a 70% increased risk for death associated with pregnancy (aRR = 1.7; 95% CI = 1.2–2.4). Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35–44 years than among those aged 15–24 years (Table 2). Whereas non-Hispanic Black or African American (Black) women made up 14.1% of women included in this analysis, they represented 176 (36.6%) deaths overall, including nine of 34 (26.5%) deaths among pregnant women and 167 of 447 (37.4%) deaths among nonpregnant women. TABLE 2 Intensive care unit (ICU) admissions, receipt of invasive ventilation, receipt of extracorporeal membrane oxygenation (ECMO), and deaths among symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 (N = 409,462), by pregnancy status, age, race/ethnicity, and underlying health conditions — United States, January 22–October 3, 2020 Outcome*/Characteristic No. (per 1,000 cases) of symptomatic women Risk ratio (95% CI) Pregnant (n = 23,434) Nonpregnant (n = 386,028) Crude† Adjusted†,§ ICU admission¶ All 245 (10.5) 1,492 (3.9) 2.7 (2.4–3.1) 3.0 (2.6–3.4) Age group, yrs 15–24 49 (7.6) 244 (1.8) 4.1 (3.0–5.6) 3.9 (2.8–5.3) 25–34 118 (9.1) 467 (3.5) 2.6 (2.1–3.1) 2.4 (2.0–3.0) 35–44 78 (19.4) 781 (6.4) 3.0 (2.4–3.8) 3.2 (2.5–4.0) Race/Ethnicity Hispanic or Latina 89 (12.8) 429 (5.0) 2.6 (2.0–3.2) 2.8 (2.2–3.5) AI/AN, non-Hispanic 0 (0) 13 (7.9) NA NA Asian, non-Hispanic 20 (35.7) 52 (6.0) 5.9 (3.6–9.8) 6.6 (4.0–11.0) Black, non-Hispanic 46 (13.6) 334 (6.2) 2.2 (1.6–3.0) 2.8 (2.0–3.8) NHPI, non-Hispanic 5 (42.0) 22 (14.4) 2.9 (1.1–7.6) 3.7 (1.3–10.1) White, non-Hispanic 31 (5.6) 348 (2.8) 2.0 (1.4–2.9) 2.3 (1.6–3.3) Multiple or other race, non-Hispanic 8 (11.0) 37 (3.0) 3.7 (1.7–7.9) 4.1 (1.9–8.9) Unknown/Not reported 46 (7.6) 257 (2.6) 2.9 (2.1–3.9) 3.4 (2.5–4.7) Underlying health conditions Diabetes 25 (58.5) 274 (44.8) 1.3 (0.9–1.9) 1.5 (1.0–2.2) CVD** 13 (42.8) 247 (32.1) 1.3 (0.8–2.3) 1.5 (0.9–2.6) Chronic lung disease 15 (29.6) 179 (19.5) 1.5 (0.9–2.6) 1.7 (1.0–2.8) Invasive ventilation†† All 67 (2.9) 412 (1.1) 2.7 (2.1–3.5) 2.9 (2.2–3.8) Age group, yrs 15–24 11 (1.7) 68 (0.5) 3.3 (1.8–6.3) 3.0 (1.6–5.7) §§ 25–34 30 (2.3) 123 (0.9) 2.5 (1.7–3.7) 2.5 (1.6–3.7) §§ 35–44 26 (6.5) 221 (1.8) 3.5 (2.4–5.3) 3.6 (2.4–5.4) Race/Ethnicity Hispanic or Latina 33 (4.7) 143 (1.7) 2.8 (1.9–4.1) 3.0 (2.1–4.5) AI/AN, non-Hispanic 0 (0) 5 (3.0) NA NA Asian, non-Hispanic 4 (7.1) 19 (2.2) NA NA Black, non-Hispanic 10 (3) 86 (1.6) 1.9 (1.0–3.6) 2.5 (1.3–4.9) NHPI, non-Hispanic 4 (33.6) 10 (6.6) NA NA White, non-Hispanic 12 (2.2) 102 (0.8) 2.7 (1.5–4.8) 3.0 (1.7–5.6) Multiple or other race, non-Hispanic 0 (0) 8 (0.6) NA NA Unknown/Not reported 4 (0.7) 39 (0.4) NA NA Underlying health conditions Diabetes 10 (23.4) 98 (16.0) 1.5 (0.8–2.8) 1.7 (0.9–3.3) CVD** 6 (19.7) 82 (10.6) 1.9 (0.8–4.2) 1.9 (0.8–4.5) ¶¶ Chronic lung disease 4 (7.9) 50 (5.4) NA NA ECMO*** All 17 (0.7) 120 (0.3) 2.3 (1.4–3.9) 2.4 (1.5–4.0) Age group,yrs 15–24 6 (0.9) 31 (0.2) 4.0 (1.7–9.5) NA††† 25–34 7 (0.5) 35 (0.3) 2.0 (0.9–4.6) 2.0 (0.9–4.4) §§ 35–44 4 (1.0) 54 (0.4) NA NA Race/Ethnicity Hispanic or Latina 6 (0.9) 35 (0.4) 2.1 (0.9–5.0) 2.4 (1.0–5.9) AI/AN, non-Hispanic 0 (0) 1 (0.6) NA NA Asian, non-Hispanic 0 (0) 1 (0.1) NA NA Black, non-Hispanic 5 (1.5) 30 (0.6) 2.7 (1.0–6.9) 2.9 (1.1–7.3) NHPI, non-Hispanic 0 (0) 2 (1.3) NA NA White, non-Hispanic 4 (0.7) 29 (0.2) NA NA Multiple or other race, non-Hispanic 0 (0) 3 (0.2) NA NA Unknown/Not reported 2 (0.3) 19 (0.2) NA NA Underlying health conditions Diabetes 1 (2.3) 13 (2.1) NA NA CVD** 1 (3.3) 20 (2.6) NA NA Chronic lung disease 1 (2.0) 20 (2.2) NA NA Death§§§ All 34 (1.5) 447 (1.2) 1.3 (0.9–1.8) 1.7 (1.2–2.4) Age group, yrs 15–24 2 (0.3) 40 (0.3) NA NA 25–34 15 (1.2) 125 (0.9) 1.2 (0.7–2.1) 1.2 (0.7–2.1) 35–44 17 (4.2) 282 (2.3) 1.8 (1.1–3.0) 2.0 (1.2–3.2) Race/Ethnicity Hispanic or Latina 14 (2.0) 87 (1.0) 2.0 (1.1–3.5) 2.4 (1.3–4.3) AI/AN, non-Hispanic 0 (0) 5 (3.0) NA NA Asian, non-Hispanic 1 (1.8) 11 (1.3) NA NA Black, non-Hispanic 9 (2.7) 167 (3.1) 0.9 (0.4–1.7) 1.4 (0.7–2.7) NHPI, non-Hispanic 2 (16.8) 6 (3.9) NA NA White, non-Hispanic 3 (0.5) 83 (0.7) NA NA Multiple or other race, non-Hispanic 0 (0) 12 (1.0) NA NA Unknown/Not reported 5 (0.8) 76 (0.8) 1.1 (0.4–2.6) 1.4 (0.6–3.6) Underlying health conditions Diabetes 6 (14.1) 78 (12.7) 1.1 (0.5–2.5) 1.5 (0.6–3.5) ¶¶¶ CVD** 7 (23.0) 89 (11.6) 2.0 (0.9–4.3) 2.2 (1.0–4.8)**** Chronic lung disease 1 (2.0) 37 (4.0) NA NA Abbreviations: AI/AN = American Indian/Alaska Native; CI = confidence interval; CVD = cardiovascular disease; NA = not applicable; NHPI = Native Hawaiian or Other Pacific Islander. * Percentages calculated among total in pregnancy status group. † Crude and adjusted risk ratios were not calculated for cell sizes <5. § Adjusted for age (continuous variable, in years), categorical race/ethnicity variable, and dichotomous indicators for diabetes, cardiovascular disease, and chronic lung disease. ¶ A total of 17,007 (72.6%) symptomatic pregnant women and 291,539 (75.5%) symptomatic nonpregnant women were missing information on ICU admission status; however, while hospital admission status was not separately analyzed, hospitalization status was missing for 2,393 (10.2%) symptomatic pregnant women and 35,624 (9.2%) of symptomatic nonpregnant women, and no hospital admission was reported for 16,672 (71.1%) pregnant and 337,414 (87.4%) nonpregnant women. Therefore, in the absence of reported hospital admissions, women with missing ICU admission information were assumed to have not been admitted to the ICU. ** Cardiovascular disease also accounts for presence of hypertension. †† A total of 17,903 (76.4%) pregnant women and 299,413 (77.6%) nonpregnant women were missing information regarding receipt of invasive ventilation and were assumed to have not received it. §§ Adjusted for the presence of diabetes, CVD, and chronic lung disease only, and removed race/ethnicity from adjustment set because of model convergence issues . ¶¶ Adjusted for the presence of diabetes and chronic lung disease and age as a continuous covariate only and removed race/ethnicity from adjustment set because of model convergence issues. *** A total of 18,246 (77.9%) pregnant women and 298,608 (77.4%) nonpregnant women were missing information for receipt of ECMO and were assumed to have not received ECMO. ††† Model failed to converge even after adjustment for a reduced set of covariates. §§§ A total of 5,152 (22.0%) pregnant women and 66,346 (17.2%) nonpregnant women were missing information on death and were assumed to have survived. ¶¶¶ Adjusted for the presence of CVD and chronic lung disease and age as a continuous variable. **** Adjusted for presence of diabetes and chronic lung disease and age as a continuous variable. Increased risk for ICU admission among pregnant women was observed for all strata but was particularly notable among non-Hispanic Asian (Asian) women (aRR = 6.6; 95% CI = 4.0–11.0) and non-Hispanic Native Hawaiian/Pacific Islander women (aRR = 3.7; 95% CI = 1.3–10.1). Risk for receiving invasive ventilation among pregnant women aged 15–24 years was 3.0 times that of nonpregnant women (95% CI = 1.6–5.7), and among pregnant women aged 35–44 years was 3.6 times that of nonpregnant women (95% CI = 2.4–5.4). In addition, among Hispanic women, pregnancy was associated with 2.4 times the risk for death (95% CI = 1.3-4.3) (Table 2). Discussion Although the absolute risks for severe COVID-19–associated outcomes among women were low, pregnant women were at significantly higher risk for severe outcomes compared with nonpregnant women. This finding might be related to physiologic changes in pregnancy, including increased heart rate and oxygen consumption, decreased lung capacity, a shift away from cell-mediated immunity, and increased risk for thromboembolic disease ( 4 , 5 ). Compared with the initial report of these data ( 1 ), in which increased risk for ICU admissions and invasive ventilation among pregnant women was reported, this analysis includes nearly five times the number of symptomatic women and a higher proportion of women with known pregnancy status (36% versus 28%). Further, to avoid including pregnant women who were tested as part of asymptomatic screening practices at the delivery hospitalization, this analysis was limited to symptomatic women. In this analysis 5.7% of symptomatic women aged 15–44 years with COVID-19 were pregnant, corresponding to the anticipated proportion of 5% of the population at any point in time. ¶¶ , *** Whereas increased risk for severe disease related to pregnancy was apparent in nearly all stratified analyses, pregnant women aged 35–44 years with COVID-19 were nearly four times as likely to require invasive ventilation and twice as likely to die than were nonpregnant women of the same age. Among symptomatic pregnant women with COVID-19 for whom race/ethnicity was reported, 30% were Hispanic and 24% were White, differing from the overall reported racial/ethnic distribution of women who gave birth in 2019 (24% Hispanic and 51% White). ††† Pregnant Asian and Native Hawaiian/Pacific Islander women appeared to be at disproportionately greater risk for ICU admission. Hispanic pregnant women of any race not only experienced a disproportionate risk for SARS-CoV-2 infection but also a higher risk for death compared with nonpregnant Hispanic women. Regardless of pregnancy status, non-Hispanic Black women experienced a disproportionate number of deaths relative to their distribution among reported cases. This analysis highlights racial and ethnic disparities in both risk for infection and disease severity among pregnant women, indicating a need to address potential drivers of risk in these populations. The findings in this report are subject to at least three limitations. First, national case surveillance data for COVID-19 are voluntarily reported to CDC and rely on health care providers and jurisdictional public health agencies to share information for patients who meet standard case definitions. The mechanism used to report cases and the capacity to investigate cases varies across jurisdictions. §§§ Thus, case information is limited or unavailable for a portion of detected COVID-19 cases, and reported case data might be updated at any time. This analysis was restricted to women with known age; however, pregnancy status was missing for over one half (64.5%) of reported cases, and among those with known pregnancy status, data on race/ethnicity were missing for approximately 25% of cases, and information on symptoms and underlying conditions was missing for approximately one half. Second, when estimating the proportion of cases with severe outcomes, the observational data collected through passive surveillance might be subject to reporting bias, wherein preferential ascertainment of severe cases is likely ( 6 , 7 ); therefore, the frequency of reported outcomes incorporates a denominator of all cases as a conservative estimate. Finally, severe outcomes might require additional time to be ascertained. To account for this, a time lag was incorporated, such that data reported as of October 28, 2020, were used for cases reported as of October 3. This analysis supports previous findings that pregnancy is associated with increased risk for ICU admission and receipt of invasive ventilation among women of reproductive age with COVID-19 ( 1 , 2 ). In the current report, an increased risk for receiving ECMO and death was also observed, which are two additional important markers of COVID-19 severity that support previous findings. In comparison to influenza, a recent meta-analysis found no increased risk for ICU admission or death among pregnant women with seasonal influenza ( 8 ). However, data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy ( 9 ). Longitudinal surveillance and cohort studies among pregnant women with COVID-19, including information about pregnancy outcomes, are necessary to understand the full spectrum of maternal and neonatal outcomes associated with COVID-19 in pregnancy. CDC, in collaboration with health departments, has adapted SET-NET to collect pregnancy-related information and pregnancy and neonatal outcomes among women with COVID-19 during pregnancy ¶¶¶ ( 3 ). Understanding the risk posed by SARS-CoV-2 infection in pregnant women can inform clinical practice, risk communication, and medical countermeasure allocation. Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19.**** To minimize the risk for acquiring SARS-CoV-2 infection, pregnant women should limit unnecessary interactions with persons who might have been exposed to or are infected with SARS-CoV-2, including those within their household, †††† as much as possible. §§§§ When going out or interacting with others, pregnant women should wear a mask, social distance, avoid persons who are not wearing a mask, and frequently wash their hands. In addition, pregnant women should take measures to ensure their general health, including staying up to date with annual influenza vaccination and prenatal care. Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy. ¶¶¶¶ , ***** Additional data from surveillance and cohort studies on COVID-19 severity during pregnancy are necessary to inform messaging and patient counseling. Summary What is already known about this topic? Limited information suggests that pregnant women with COVID-19 might be at increased risk for severe illness compared with nonpregnant women. What is added by this report? In an analysis of approximately 400,000 women aged 15–44 years with symptomatic COVID-19, intensive care unit admission, invasive ventilation, extracorporeal membrane oxygenation, and death were more likely in pregnant women than in nonpregnant women. What are the implications for public health practice? Pregnant women should be counseled about the risk for severe COVID-19–associated illness including death; measures to prevent infection with SARS-CoV-2 should be emphasized for pregnant women and their families. These findings can inform clinical practice, risk communication, and medical countermeasure allocation.

The omicron variant of SARS-CoV-2 (PANGO B.1.1.529) spread rapidly across the world, out-competing former variants soon after it was first detected in November, 2021. According to the Our World in Data COVID-19 database, In Europe, the number of confirmed cases reported between December, 2021, and March, 2022 (omicron period) has exceeded all previously reported cases. Omicron appears to cause less severe acute illness than previous variants, at least in vaccinated populations. However, the potential for large numbers of people to experience long-term symptoms is a major concern, and health and workforce planners need information urgently to appropriately scale resource allocation. In this case-control observational study, we set out to identify the relative odds of long-COVID (defined following the National Institute for Health and Care Excellence guidelines as having new or ongoing symptoms 4 weeks or more after the start of acute COVID-19) in the UK during the omicron period compared with the delta period. We used self-reported data from the COVID Symptom Study app 1 (King's College London Research Ethics Management Application System number 18210, reference LRS-19/20-18210). Data were extracted and pre-processed using ExeTera13 (version 0.5.5). The inclusion criteria in both periods were a positive real-time PCR or lateral flow antigen test for SARS-CoV-2 after vaccination, at least one log per week in the app for at least 28 days after testing positive, 2 and no previous SARS-CoV-2 infections before vaccination. We identified 56 003 UK adults first testing positive between Dec 20, 2021, and March 9, 2022, who satisfied the inclusion criteria. These cases are hereafter referred to as omicron cases as more than 70% of UK cases were estimated to be attributable to the omicron variant during that time. Using identical selection criteria, we identified 41 361 UK adult cases first testing positive between June 1, 2021, and Nov 27, 2021, referred to as delta cases as more than 70% of cases were attributable to the delta variant. Both symptomatic and asymptomatic infections were considered, and, for the omicron period, we included only participants testing positive before Feb 10, 2022, to ensure all participants had at least 28 days for symptom reporting after testing positive. In both periods, female participation was higher than male participation (55% for omicron and 59% for delta cases). Delta and omicron cases had similar age (mean age 53 years) and prevalence of comorbidities (around 19%). Considering the local area Index of Multiple Deprivation (IMD), a score ranging from 1 (most deprived) to 10 (least deprived) estimating relative locality deprivation, omicron cases were distributed in areas of slightly lower deprivation than delta cases (16·7% vs 17·5% for IMD 1–3). To assess the association between long COVID (outcome) and the infection period (exposure), we applied a univariate logistic regression model adjusted by sex, IMD, age, the presence of comorbidities, vaccination status (one, two, or three doses), and body-mass index, all of which are related to the risk of long COVID. 3 We stratified the analysis according to the time elapsed between infection and most recent vaccination considering three groups, 3 months, 3–6 months, and more than 6 months, to allow for potential waning of immunity from vaccination. Among omicron cases, 2501 (4·5%) of 56 003 people experienced long COVID and, among delta cases, 4469 (10·8%) of 41 361 people experienced long COVID. Omicron cases were less likely to experience long COVID for all vaccine timings, with an odds ratio ranging from 0·24 (0·20–0·32) to 0·50 (0·43–0·59). These results were also confirmed when the analysis was stratified by age group (figure ). Figure Odds ratio of long COVID (LC) adjusted by age, sex, body-mass index, Index of Multiple Deprivation, presence of comorbidities, and vaccination status Omicron long COVID and delta long COVID indicate, for each stratum, the number of users with long COVID over the total number of users of that stratum. We believe this is the first peer-reviewed study to report on long COVID risk associated with infection by the omicron variant, highlighting that health surveillance using smartphone apps can produce rapid insights, which we have consistently shown are accurate and subsequently replicated. 1 A major strength of our study in relation to long COVID is the prospective symptom logging of a wide range of symptoms. Limitations of the self-reported data include no direct testing of infectious variants (here assumed from national data) and no objective measures of illness duration. The samples, although not fully generalisable to the UK population on account of sex and socioeconomic bias, were similar in both periods, allowing comparison. We had insufficient data to estimate the odds of long COVID in unvaccinated individuals and did not estimate effects in children. Finally, to enable swift reporting, the period of assessment of omicron cases was slightly shorter than for the delta variant, and assessment of longer durations of long COVID (eg, >12 weeks) was not possible. Overall, we found a reduction in odds of long COVID with the omicron variant versus the delta variant of 0·24–0·50 depending on age and time since vaccination. However, the absolute number of people experiencing long COVID at a given time depends on the shape and amplitude of the pandemic curve. For example, given the high numbers of people infected with omicron in the UK from December, 2021, to February, 2022, our data are consistent with the UK Office for National Statistics, who estimated that the numbers of people experiencing long COVID actually increased from 1·3 million in January, 2022, to 1·7 million in March, 2022. 4 Considering the UK omicron peak of more than 350 000 new symptomatic COVID-19 cases per day estimated on March 26, 2022, by the ZOE app model and 4% of cases being long COVID, future numbers with long COVID will inevitably rise. For Our World In Data COVID-19 data see https://ourworldindata.org/coronavirus