Pregnancy may provide some protection against Long COVID

Pregnancy may offer some protection from developing Long COVID, found a new study led by Weill Cornell Medicine, University of Rochester Medical Center, University of Utah Health and Louisiana Public Health Institute. Previous research has mostly focused on non-pregnant adults affected by Long COVID- a condition lasting for months after a person recovers from SARS-CoV-2 infection.

The study, published April 1 in Nature Communications, helps fill a critical gap about Long COVID in women infected with SARS-CoV-2 during pregnancy. "This population is so important and vulnerable, but we had no evidence about their Long COVID risk to guide their care," said Dr. Chengxi Zang, an instructor in population health sciences at Weill Cornell Medicine, who co-led the research. "We hope this new data will help clinicians develop better Long COVID prevention and treatment strategies for pregnant women and help those most at risk."

Digging into data

The researchers tapped into real-world data collected in two large electronic health record-based studies, the National Patient-Centered Clinical Research Network (PCORnet) and the National COVID Cohort Collaborative (N3C), under the National Institutes of Health RECOVER initiative. They analyzed data on approximately 72,000 women who were infected with SARS-CoV-2 during pregnancy between March 2020 and June 2023 and about 208,000 age and demographically matched controls who were not pregnant but developed the infection during this period. They looked for signs of Long COVID 180 days after the women recovered from infections.

The team found that the rates of long-term complications related to COVID-19 are lower among pregnant women than comparably matched women who were not pregnant during their infection. The findings were consistent across both large databases and held true even when the researchers used different methods to define Long COVID. This consistency adds confidence to the results.

In the PCORnet cohort, Dr. Zang and his colleagues found that about 16 out of 100 pregnant women developed Long COVID compared with about 19 out of 100 non-pregnant women. Long COVID is defined as having any of the following symptoms: cognitive problems, encephalopathy, sleep disorders, acute pharyngitis, shortness of breath, pulmonary fibrosis, chest pain, diabetes, edema, malnutrition, joint pain, fever, malaise and fatigue. Similar findings were replicated in the N3C cohort.

Though we observed that pregnant women have a significant risk of Long COVID, it was surprisingly lower than those who were not pregnant when they had SARS-CoV-2 infection. However, some subgroups seemed especially vulnerable."

Dr. Chengxi Zang

Groups at higher risk

Among the pregnant women, the researchers found that certain groups had higher Long COVID risks than others. For example, pregnant women who identified as Black, or were of advanced maternal age (age 35 or older at delivery), or had obesity or other metabolic conditions were more likely to develop Long COVID than pregnant women who weren't part of these groups. However, this risk was still lower than their matched non-pregnant controls.

"Further research on factors such as inequitable healthcare access, socioeconomic factors and structural racism may help us understand the elevated Long COVID risk in these groups and find ways to protect them," said Dr. Zang.

"We hypothesize that the altered immune and inflammatory environment lasting about six weeks after giving birth might contribute to lowering the risk of Long COVID," Dr. Zang said, "The observed risk differences in this analysis suggest future dedicated studies of Long COVID in pregnant individuals are needed." For instance, differences in COVID infection by trimester may be informative for patient counseling.

Dr. Zang and his colleagues at Weill Cornell Medicine are also using electronic health records to study how existing medications may be repurposed to protect pregnant women from Long COVID.

This study was co-led by Dr. Elaine Hill and Dr. Daniel Guth, at the University of Rochester Medical Center; Dr. Torri D. Metz and Dr. Ann Bruno at the University of Utah Health; and Thomas Carton at Louisiana Public Health Institute.