The recent study published in *EClinicalMedicine* investigated 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), commonly known as Long COVID, compared to infection outside of pregnancy.
Background
As the COVID-19 pandemic has evolved, the short-term impacts of SARS-CoV-2 infection are well-documented. However, attention is now focused on understanding the long-term health effects, termed PASC or Long COVID. Defined by the World Health Organization (WHO) as symptoms appearing within three months post-infection and lasting at least two months, PASC can affect almost every organ system. About one-third of COVID-19 patients may develop PASC, but its impact following infection during pregnancy, which is associated with adverse perinatal outcomes and increased maternal morbidity, remains less understood.
About the Study
The study utilized data from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centered Clinical Research Network (PCORnet), which encompasses electronic health records (EHRs) of approximately 10 million patients across 19 U.S. health systems. The retrospective cohort study included women aged 18-49 with lab-confirmed SARS-CoV-2 infection between March 1, 2020, and June 1, 2022. The primary exposure variable was SARS-CoV-2 infection during pregnancy, identified using ICD-10 codes and validated algorithms.
The primary outcome measured was the occurrence of PASC within 30 to 180 days post-infection. Secondary outcomes included 24 specific conditions such as diabetes, thromboembolism, headache, and cognitive issues. Statistical analyses included univariable comparisons of baseline characteristics and comorbidities, with COVID-19 severity assessed by care location and ICU admission.
Using stabilized inverse probability of treatment weighting, the study modeled the association between infection during pregnancy and PASC, providing adjusted hazard ratios (aHR) and cumulative incidence (CI) at 180 days. Sensitivity analyses excluded thromboembolism and pulmonary embolism and employed a propensity match approach. The study adhered to STROBE guidelines and received IRB approval, using de-identified data with a waiver of consent.
Study Results
The study included 83,915 women who acquired SARS-CoV-2 outside of pregnancy and 5,397 women who acquired it during pregnancy. Women infected outside of pregnancy tended to be older, non-Hispanic White, and more likely to be fully vaccinated against COVID-19, with higher incidences of comorbidities like chronic hypertension and obesity. Women infected during pregnancy were more likely to need inpatient care. The median gestational age at infection was 34 weeks, and delivery occurred at a median of 39 weeks.
The IPTW analysis adjusted for baseline covariates indicated that 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 was 30.8 per 100 persons for those infected during pregnancy, versus 35.8 per 100 persons for those infected outside of pregnancy.
When examining specific diagnoses, infection during pregnancy was linked to lower incidences 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, higher incidences of abnormal heartbeat, abdominal pain, and thromboembolism were observed in the pregnant group.
Sensitivity Analyses
Excluding thromboembolism and pulmonary embolism, 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 propensity score matching analysis confirmed these findings (aHR 0.76, 95% CI 0.71–0.82).
Conclusions
The study suggests that while pregnancy increases the risk for certain acute complications of SARS-CoV-2 infection, it appears to offer a protective effect against the development of PASC in the months following infection. Specifically, symptoms like joint pain, sleep disorders, and cognitive problems were less common among those infected during pregnancy, although risks for thromboembolism, abdominal pain, and abnormal heartbeat were higher.
These findings highlight the need for targeted interventions and further research to understand and mitigate the unique impacts of SARS-CoV-2 infection during pregnancy.
