This article is part of our May 2023 Immune Health special issue. Download the full issue here.
Reference
Oliviera AMDSS, Carvahlo MA, Nacul L, et al. Post-viral fatigue following SARS-CoV-2 infection during pregnancy: a longitudinal comparative study. Int J Environ Res Public Health. 2022;19(23):15735.
Study Objective
To determine the prevalence, duration, and risk factors of postviral fatigue among pregnant women with SARS-CoV-2
Key Takeaway
The risk and duration of post-Covid fatigue during pregnancy increase relative to the severity of the infection.
Design
Longitudinal comparative study
Participants
Investigators studied 3 groups of pregnant women (N=588):
- Group 1 (G1): women diagnosed with Covid-19 infection during pregnancy (n=259)
- Group 2 (G2): women who were not tested for Covid-19 during pregnancy and who had a positive Covid-19 serology at delivery (n=131)
- Group 3 (G3): women who were not tested during pregnancy and had a negative serology at delivery (n=198)
Women who were vaccinated for Covid-19 were excluded from the study.
Study Parameters Assessed
All women received questionnaires for fatigue evaluation at delivery and at 6 weeks, 3 months, and 6 months after delivery. Group 1 also received questionnaires at 6 weeks, 3 months, and 6 months after Covid-19 diagnosis. Investigators reviewed obstetrical charts for medical history.
The questionnaire determined the presence or absence of mental or physical fatigue, pain, and loss of normal activity. For women with “significant fatigue,” the investigators gave a follow-up questionnaire to further understand the symptoms. This gathered further data on comorbidities or other possible causes of fatigue.
Fatigue and associated symptoms were graded on a scale of 1 to 10. If a woman reported feeling fatigue more than 50% of the time, this was considered “fatigue most of the time,” and if she also reported being able to perform less than half of her normal activities, this was considered “significant fatigue.”
Women from group 1 were further divided into 3 groups based on the severity of their Covid-19 symptoms: those with mild symptoms, those with moderate symptoms who needed hospital admission for oxygen, and those with severe symptoms who required hospitalization and mechanical ventilation or who had multi-organ involvement. Investigators compared the severity of Covid-19 symptoms with the prevalence, severity, and duration of fatigue.
Primary Outcome
This study was designed to assess prevalence, duration, and risk factors for fatigue in women who contract Covid-19 during pregnancy.
Key Findings
In G1, of the women who followed up, 40.6% reported fatigue at 6 weeks postdiagnosis, 33.6% at 3 months, and 27.8% at 6 months. Women who had severe cases of Covid-19 had a significantly higher risk (HR=2.43; 95% CI, 1.49–3.95; P<0.001) of fatigue relative to those with mild disease. G2 did not report significant fatigue relative to G3.
Symptoms of cough (HR=1.76; 95% CI, 1.07–2.96; P=0.024) and myalgia (HR=1.57; 95% CI, 1.01–2.44; P=0.060) were associated with greater fatigue over time; anosmia (HR=0.60; 95% CI, 0.40–0.88; P=0.033) was associated with a lower incidence of fatigue. Comorbidities such as hypertension, cardiac disease, and lung disease were not associated with persistent fatigue.
Transparency
This study was funded by HCCOMVIDA-Chamada and the EU Horizon 2020 Research and Innovation Programme under the ZIKAlliance Grant Agreement. The funders were not involved in data collection or manuscript preparation.
Practice Implications & Limitations
This study did not clarify whether pregnant women are more likely to experience post-Covid fatigue, primarily because there are no clear data on how common it is in the general public.1
However, it raised interesting subtleties about what may lead to post-Covid syndrome. First, it showed that the women who tested positive for Covid-19 during childbirth but had no symptoms did not have fatigue. Further, it correlated greater severity of Covid symptoms with more fatigue. It also brought to light a few important questions around how we can support our pregnant patients relative to Covid risk.
There is wide variability in the data around post-Covid fatigue in the general public:2 This study cites a range anywhere from 15% to 87%. This makes it difficult to evaluate whether this pregnant population had higher or lower rates of post-Covid fatigue than other groups. One meta-analysis of 68 studies found a 32% rate of post-Covid fatigue 12 weeks after diagnosis, which is similar to the rate found in the G1 cohort of this study.3 This suggests a similar rate of post-Covid fatigue in pregnancy relative to that of the general population.
Fatigue, however, is subjective and difficult to define. Also, it can be hard to distinguish whether fatigue in postpartum women is due to post-Covid syndrome. During the postpartum period, women are recovering from labor, coping with lack of sleep, feeding, and tending to the needs of an infant. It may be difficult to tease out what is post-Covid fatigue and what is simply due to the nature of being the mother of a newborn.4,5
Additionally, many other common postpartum disorders can cause fatigue, including anemia, other infections, thyroid disorder, mood disorders, and cardiomyopathy. Another thing to keep in mind is what the study missed due to a low visit-completion rate. In G1, 67.6% of the initial group followed up at 6 weeks, 48.2% at 3 months, and 30.5% at 6 months. The authors report that this cohort was generally of low socioeconomic status and may have had difficulty using public transport during the pandemic to travel to follow-up appointments, so we do not know what symptoms went unreported.
Women who tested positive for Covid-19 during childbirth but had no symptoms did not have fatigue.
While this study does not definitively show that pregnant women are more susceptible to post-Covid fatigue, it does correlate the severity of Covid-19 disease with fatigue. This is important because, while it is inconclusive whether pregnancy increases susceptibility to Covid, pregnancy is correlated with higher rates of severe Covid infection and increased occurrence of negative maternal-fetal outcomes.6-9 With this in mind, it is important to consider which pregnant patients might be more likely to contract a severe case of Covid. While hypertension and lung disease were not correlated with post-Covid fatigue in this study, a higher percentage of the women in this study who had these comorbidities were in G1. Also, while none of the subjects in G1 with fatigue were diabetic, other studies have found higher rates of post-Covid fatigue in type 2 diabetics.10
Another interesting point brought up by this study is that a positive SARS-CoV-2 serology in the absence of symptoms is not associated with post-Covid symptoms. In this study, the more severe the Covid symptoms, the more severe the fatigue. Other studies have found that it is not the level of SARS-CoV-2 virus but rather the amount of inflammatory proteins present that correlates with severity of disease and post-Covid symptoms such as fatigue.11
When we have pregnant patients in the office asking about Covid, it is worth considering both the increased potential for negative outcomes and any other health concerns they may have. We can reassure them that if they have a mild case of Covid, there is no correlation with fatigue. So patients do not need to worry if they have tested positive for Covid but have not had symptoms or had symptoms mild enough to avoid hospitalization.
With that said, anything we can do as clinicians for our pregnant patients to decrease the likelihood of contracting Covid or the severity of their symptoms is highly beneficial. This includes offering vaccination as an option, as this decreases the occurrence of these negative outcomes.12
