In a recent study published in the journal EClinicalMedicine, a group of researchers evaluated the association between acquiring Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during pregnancy and the development of post-acute sequelae of SARS-CoV-2 infection (PASC) compared to infection outside of pregnancy.

Study: Association between acquiring SARS-CoV-2 during pregnancy and post-acute sequelae of SARS-CoV-2 infection: RECOVER electronic health record cohort analysis. Image Credit: Donkeyworx / Shutterstock

Background 

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, the short-term course and complications of SARS-CoV-2 infection are well-documented. Attention is now focused on understanding the long-term health effects, known as PASC or Long COVID. The World Health Organisation (WHO) defines PASC as symptoms occurring within three months post-infection, lasting at least two months, and not explained by other diagnoses. PASC affects nearly every organ system, with studies indicating that one-third of COVID-19 patients may develop PASC. However, little is known about PASC following SARS-CoV-2 infection during pregnancy, which is linked to worse perinatal outcomes and maternal morbidity. Further research is necessary to understand its unique impact and to develop targeted interventions for this population.

About the study 

The present retrospective cohort study used data from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centered Clinical Research Network (PCORnet) electronic health record (EHR) dataset, which includes records for about 10 million patients across 19 United States (U.S.) health systems. The study included females aged 18-49 with lab-confirmed SARS-CoV-2 infection between March 1, 2020, and June 1, 2022. The primary exposure was SARS-CoV-2 infection during pregnancy versus outside of pregnancy, identified using International Classification of Diseases Tenth Revision (ICD-10) codes and validated algorithms.

The primary outcome was PASC within 30 to 180 days post-infection, based on a previously established phenotype excluding anemia. Secondary outcomes included 24 conditions such as diabetes, thromboembolism, headache, and cognitive problems. Univariable comparisons of baseline characteristics and comorbidities were performed between the two groups, and COVID-19 severity was assessed by care location and intensive care unit (ICU) admission.

Using the stabilized inverse probability of treatment weighting, the study modeled the association between infection during pregnancy and PASC, reporting adjusted hazard ratios (aHR) and cumulative incidence (CI) at 180 days. Sensitivity analyses excluded thromboembolism and pulmonary embolism and used a propensity match approach. Bonferroni correction adjusted for multiple comparisons, with significance set at p < 0.05. Analyses were conducted using Python 3.9. The study followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and received institutional review board (IRB) approval using de-identified data with a waiver of consent.

Study results 

A total of 83,915 females with SARS-CoV-2 infection acquired outside of pregnancy and 5,397 females with SARS-CoV-2 infection acquired during pregnancy were identified and included in the analysis. Females with SARS-CoV-2 infection outside of pregnancy were more likely to be older, non-Hispanic White, have documented full COVID-19 vaccination, and have comorbid conditions such as chronic hypertension, chronic kidney disease, and class III obesity. Conversely, females with SARS-CoV-2 infection during pregnancy were more likely to require inpatient management for COVID-19. Among these pregnant females, the median gestational age at infection was 34 weeks, and the median gestational age at delivery was 39 weeks.

In the stabilized inverse probability of treatment weighting (IPTW) analysis adjusted for baseline covariates, acquiring SARS-CoV-2 infection during pregnancy was associated with a lower incidence of PASC in the subsequent 30-180 days compared to infection outside of pregnancy (25.5% vs. 33.9%; aHR 0.85, 95% CI 0.80–0.91; p < 0.001). The CI of PASC in the 180 days following the infection was 30.8 per 100 persons among those infected during pregnancy, compared to 35.8 per 100 persons among those infected outside of pregnancy.

When examining the 24 component diagnoses contributing to the PASC phenotype, SARS-CoV-2 infection during pregnancy was associated with a lower incidence of joint pain, sleep disorders, cognitive problems, dyspnea, encephalopathy, hair loss, acute pharyngitis, malnutrition, malaise and fatigue, chest pain, and ICD-10 code-defined PASC. However, infection during pregnancy was linked to a higher incidence of abnormal heartbeat, abdominal pain, and thromboembolism.

In a sensitivity analysis excluding thromboembolism and pulmonary embolism from the PASC definition, SARS-CoV-2 infection during pregnancy still resulted in a lower incidence of PASC (25.2% vs. 33.7%; aHR 0.84, 95% CI 0.79–0.90; corrected p < 0.001). A second sensitivity analysis using propensity score matching confirmed that infection during pregnancy remained associated with a lower incidence of PASC (aHR 0.76, 95% CI 0.71–0.82). 

Conclusions 

To summarize, the study findings suggest that while pregnancy may increase the risk for certain acute complications of SARS-CoV-2 infection, it appears to confer a protective effect against the development of PASC in the months following infection. Symptoms like joint pain, sleep disorders, and cognitive problems were less frequent among those infected during pregnancy. The study also noted higher incidences of thromboembolism, abdominal pain, and abnormal heartbeat in pregnant individuals.