Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts

Molteni, Erika; Astley, Christina M; Ma, Wenjie; Sudre, Carole H.; Magee, Laura A.; Murray, Benjamin; Fall, Tove; Gomez, Maria F.; Tsereteli, Neli; Franks, Paul W.; Brownstein, John S.; Davies, Richard; Wolf, Jonathan; Spector, Tim D.; Ourselin, Sébastien; Steves, Claire J.; Chan, Andrew T.; Modat, Marc

doi:10.1038/s41598-021-86452-3

Cited by 29 publications

(34 citation statements)

References 41 publications

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“…Epidemiological data from previous coronavirus outbreaks, including SARS-CoV (Severe Acute Respiratory Syndrome Corona Virus) and MERS-CoV (Middle East Respiratory Syndrome Corona Virus) showed the same pattern: among men, morbidity and fatality rates were markedly higher compared to women [3,4]. Although pregnant women are more likely to be admitted to intensive care or to receive ventilation than non-pregnant women of reproductive age [5], they generally experience milder COVID-19 symptoms than initially expected [5,6].…”

Section: Introductionmentioning

confidence: 99%

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

et al. 2021

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It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.

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Section: Introductionmentioning

confidence: 99%

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

et al. 2021

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“… 27 , 28 , 29 Studies not supporting this relationship defined “severe” disease inconsistently or based on symptoms rather than morbidity. 3 , 30 …”

Section: Epidemiology and Outcomes Of Covid‐19 During Pregnancymentioning

confidence: 99%

COVID‐19 disease and vaccination in pregnant and lactating women

Sáfadi

Spinardi²,

Swerdlow

et al. 2022

American J Rep Immunol

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Background More than 325,000 cases of coronavirus disease 2019 (COVID‐19) have been reported among pregnant women in the Americas. Aims This review examines the impact of COVID‐19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women. Content Multiple studies indicate that pregnant women are more susceptible to adverse COVID‐19 outcomes, including hospitalization, intensive care unit admission, and invasive ventilation than non‐pregnant women with COVID‐19. Furthermore, COVID‐19 in pregnancy is associated with adverse maternal and neonatal outcomes. Adverse COVID‐19 outcomes appear to disproportionately affect pregnant women from low‐ and middle‐income countries, likely reflecting inequities in access to quality healthcare. Despite the absence of safety and efficacy data from randomized clinical trials in this subpopulation, observational studies and data from pregnancy registries thus far have demonstrated that vaccination of pregnant or lactating women against COVID‐19 is safe, effective, and results in robust immune responses including transfer of antibodies to the newborn via the placenta and breast milk, respectively. Implications These data support vaccination recommendations intending to help protect these vulnerable individuals against COVID‐19 and its sequelae. Randomized clinical studies will further evaluate the safety and immunogenicity of COVID‐19 vaccines in these populations. This review examines the impact of COVID‐19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women.

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“…Through an Euclidean distance-based algorithm, 20 individuals with Delta infection were matched 1:1, based on their age and sex, with individuals with Alpha infection. We were unable to match for SARS-CoV-2 prevalence, tiered lockdown restrictions, or vaccination rates, which varied widely across the community and with time during this study.…”

Section: Covid Symptom Studymentioning

confidence: 99%

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

Kläser

Molteni

Graham

et al. 2021

Preprint

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BackgroundThe Delta (B.1.617.2) variant became the predominant UK circulating SARS-CoV-2 strain in May 2021. How Delta infection compares with previous variants is unknown.MethodsThis prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period.Findings3,581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta vs. Alpha infection (including fever, sore throat and headache) and vice versa (dyspnoea). Symptom burden in the first week was higher with Delta vs. Alpha infection; however, the odds of any given symptom lasting ≥7 days was either lower or unchanged. Illness duration ≥28 days was lower with Delta vs. Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1·47) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly (69-84%) reduced risk of Delta infection.InterpretationCOVID-19 from Delta or Alpha infections is clinically similar. The Delta variant is more transmissible than Alpha; however, current vaccines show good efficacy against disease.FundingUK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, Alzheimer’s Society, and ZOE Limited.Research in contextEvidence before this studyTo identify existing evidence for differences (including illness, transmissibility, and vaccine effectiveness) from SARS-CoV-2 infection due to Alpha (B.1.1.7) and Delta (B.1.617.2) variants, we searched PubMed for peer-reviewed articles and medRxiv for preprint publications between March 1 and November 18, 2021 using keywords (“SARS-CoV-2” OR “COVID-19”) AND (“delta variant” OR “B.1.617.2”) AND (symptom* OR transmiss* OR “disease duration” OR “illness duration” OR “symptom* duration”). Searches were not restricted by language. Among 169 identified PubMed articles, we found evidence that Delta variant has increased replication capacity (from 4-fold, up to 21-fold, compared with wild-type) and greater transmissibility (estimated between +20% and +97%), compared with previous strains. Currently available vaccines may have 2- to 5-fold lower neutralizing response to Delta vs. previous variants, depending on vaccine formulation, although their protective effect against severe disease and death appears to remain strong. REACT-1 study found that in UK infections were increasing exponentially in the 5-17-year old children in September 2021, coinciding with the start of the autumn school term in England. This was interpreted as an effect of the relatively low rate of vaccinated individuals in this age group. Other studies found that in unvaccinated individuals, Delta variant may be associated with higher odds of pneumonia, oxygen requirement, emergency care requests, ICU admission, and death. In a study of 27 (mainly young) cases, 22 persons were symptomatic, with fever (41%), cough (33%), headache (26%), and sore throat (26%) the commonest symptoms. We found no studies, beyond case series, investigating symptom and/or illness duration due to Delta variant infection otherwise.Added value of this studyUsing data from one of the largest UK citizen science epidemiological initiatives, we describe and compare illness (symptom duration, burden, profile, risk of long illness, and hospital attendance) in symptomatic community-based adults presenting when either the Alpha or Delta variant was the predominant circulating strain of SARS-CoV-2 in the UK. We assess evidence of transmission, reinfection, and vaccine effectiveness. Our data show that the seven most common symptoms with Delta infection were the same as with Alpha infection. Risks of illness duration ≥7 days and ≥28 days, and of requiring hospital care, were not increased. In line with previous research, we found increased transmissibility of Delta vs. previous variants; and no evidence of increased re-infection rates. Our data support high vaccine efficacy of BNT162b2 and ChAdOx1 nCoV-19 formulations against Delta variant infection. Overall, our study adds quantitative information regarding meaningful clinical differences in COVID-19 due to Delta vs. other variants.Implications of all the available evidenceOur observational data confirm that COVID-19 disease in UK in adults is generally comparable to infection with the Alpha variant, including in elderly individuals. Our data contribute to epidemiological surveillance from the wider UK population and may capture information from COVID-19 presentation within the community that might be missed in healthcare-based surveillance. Our data may be useful in informing healthcare service planning, vaccination policies, and measures for social protection.

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Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts

Cited by 29 publications

References 41 publications

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

COVID‐19 disease and vaccination in pregnant and lactating women

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

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