Post-COVID-19 condition in pregnant and postpartum women: a long-term follow-up, observational prospective study

Abstract

Background: Post-COVID-19 condition has recently been defined as new or persistent common COVID-19 symptoms occurring three months after disease onset. The pathology of the disease is unclear, but immune and vascular factors seem to play a significant role. The incidence, severity, and implications of the disease after COVID-19 infection in pregnancy have not been established. We aimed to study the incidence and main risk factors for post-COVID-19 condition in an obstetric population and their implications for maternal and perinatal morbimortality.

Methods: This is a prospective observational cohort study undertaken including women during pregnancy or at admission for labour with acute COVID-19 infection from March 9th, 2020 to June 11th, 2022. The inclusion criteria were confirmed acute COVID-19 infection during the recruitment period, a lack of significant language barrier and consent for follow-up. Patients were clinically followed-up by telephone via semi structured questionnaires. The exclusion criteria were loss to follow-up, spontaneous miscarriage, and legal termination of pregnancy. Patients were classified into groups according to the severity of symptoms at onset. We included patients from the first six first waves of the pandemic according to national epidemiological data in Spain. We studied the incidence of post-COVID-19 condition and their main demographic, clinical and obstetric risk factors.

Findings: A total of 409 pregnant women were recruited at acute diagnosis, and 286 were followed-up. The mean time to follow-up was 92 weeks (standard deviation ± 28 weeks; median 100 weeks (Interquartile range: 76; 112)). A total of 140 patients had at least one post-COVID-19 symptom at least three months after acute infection. Neurological (60%) and cutaneous (55%) manifestations were the most frequent findings. The following profiles were identified as presenting a higher risk of post-COVID-19 condition: migrant women born in countries with lower Human Development Index; multiparous women; women with COVID-19 during pregnancy, mainly during the first and third trimesters, and in the first and second waves of the pandemic; women who had a higher number of symptoms; women who had a higher incidence of moderate and severe symptoms; women who required hospitalisation due to COVID-19 complications; and women who were not vaccinated before disease onset. We did not find any significant difference in perinatal results, such as gestational week at delivery, birthweight, the need for neonatal care or 5-min Apgar score, and newborns benefited from a high rate of breastfeeding at discharge. Women who were infected during successive waves of the pandemic had a significant and constant decrease in the risk of post-COVID-19 condition comparing to estimated risk in the first wave (OR: 0.70; 95% CI: 0.62, 0.92). Symptoms tended to resolve over time heterogeneously. Symptoms of myalgia and arthralgia took longer to resolve (mean of 60 weeks and 54 weeks, respectively). In a small but significant proportion of patients, neurological and psycho-emotional symptoms tended to become chronic after 90 weeks.

Interpretation: At least 34.2% of obstetric patients from our cohort with acute COVID-19 infection presented post-COVID-19 condition symptoms. Demographic and acute disease characteristics as well as specific pregnancy-related risk factors were identified. This is the first study to assess post-COVID-19 condition in pregnant women. Further analysis on the biological pathophysiology of post-COVID-19 is needed to explain the characteristics of the disease.

Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/01244" and co-funded by the European Union, as well as P2022/BMD-7321 (Comunidad de Madrid) and ProACapital, Halekulani S.L. and MJR.

Keywords: COVID-19; Long COVID; Obstetrics; Perinatal; Post-COVID-19; Postpartum; Pregnancy.

Fig. 1

Study design: distribution, demographic characteristics and acute COVID-19 severity.

Fig. 2

System-clustered symptoms of post-COVID-19 conditions 3 months after the onset of acute disease (n = 140). Neurological (headache, attention deficit, insomnia, anosmia, ageusia-dysgeusia) 84 (60%). Cutaneous (skin alterations, persistent hair loss, alopecia) 77 (55%). Psycho-emotional (anxiety, depression, PTSD symptoms) 45 (32%). Cardiovascular (dyspnoea, dizziness) 31 (22%). Respiratory (cough, dyspnoea, thoracic pain) 30 (21%). Musculoskeletal (myalgia, arthralgia) 19 (14%). Digestive (weight loss, appetite loss, diarrhoea) 14 (10%).

Fig. 3

Distribution of the incidence of post-COVID-19 conditions through the different pandemic waves (x: waves of the pandemic following national data; y, right: %; y, left: n).

Fig. 4

Evolution of symptoms over time. 4.1 Musculoskeletal symptoms: Blue: Myalgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 60 weeksleft481965, Red: Arthralgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 6): median 54 weeks. 4.2 Respiratory symptoms: Blue: Dyspnoea: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 48 weeks, Red: Thoracic pain: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 5): median 48 weeks. 4.3 Cutaneous alterations: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 49): median 48 weeks. 4.4 Neurological symptoms: Blue: Attention deficit: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 21): median 48 weeks, Grey: Anosmia: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 19): median 48 weeks, Red: Headache (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 16): median 38 weeksleft20574000. 4.5 Psycho-emotional symptoms: Blue: Posttraumatic stress symptoms: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 66): median 48 weeks, Red: Psychiatric symptoms (anxiety and depression): (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 28): median 48 weeks.

Fig. 4

Evolution of symptoms over time. 4.1 Musculoskeletal symptoms: Blue: Myalgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 60 weeksleft481965, Red: Arthralgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 6): median 54 weeks. 4.2 Respiratory symptoms: Blue: Dyspnoea: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 48 weeks, Red: Thoracic pain: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 5): median 48 weeks. 4.3 Cutaneous alterations: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 49): median 48 weeks. 4.4 Neurological symptoms: Blue: Attention deficit: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 21): median 48 weeks, Grey: Anosmia: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 19): median 48 weeks, Red: Headache (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 16): median 38 weeksleft20574000. 4.5 Psycho-emotional symptoms: Blue: Posttraumatic stress symptoms: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 66): median 48 weeks, Red: Psychiatric symptoms (anxiety and depression): (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 28): median 48 weeks.

Fig. 4

Evolution of symptoms over time. 4.1 Musculoskeletal symptoms: Blue: Myalgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 60 weeksleft481965, Red: Arthralgia (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 6): median 54 weeks. 4.2 Respiratory symptoms: Blue: Dyspnoea: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 7): median 48 weeks, Red: Thoracic pain: (x: weeks of evolution; y: prevalence proportion; initial number of risk n = 5): median 48 weeks. 4.3 Cutaneous alterations: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 49): median 48 weeks. 4.4 Neurological symptoms: Blue: Attention deficit: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 21): median 48 weeks, Grey: Anosmia: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 19): median 48 weeks, Red: Headache (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 16): median 38 weeksleft20574000. 4.5 Psycho-emotional symptoms: Blue: Posttraumatic stress symptoms: (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 66): median 48 weeks, Red: Psychiatric symptoms (anxiety and depression): (x: weeks of evolution; y: prevalence proportion; initial number at risk n = 28): median 48 weeks.