Introduction

Pregnant women may be more susceptible to severe COVID-19 illness [1–3], in part due to reduced immunity and increased stress during pregnancy. Factors such as chronic stress, underlying inflammatory conditions such as obesity and asthma, belonging to a racial/ethnic minority group, and socioeconomic factors are also known to compound risk of viral infections and exacerbate inflammation during pregnancy [4–6]. Research also suggests that SARS-CoV-2 infection during pregnancy may increase risk of other adverse women’s and neonatal health outcomes [7, 8]. Despite these concerns, research on COVID-19 in pregnant women remains limited. Several studies have presented the clinical characteristics of COVID-19 in pregnant women admitted for delivery [9–15] or for COVID-19 complications [1, 16]. Fewer studies have characterized symptoms of COVID-19 in a general sample of pregnant women, representative of different stages during pregnancy [17–20]. Furthermore, prior studies have primarily focused on infection prevalence across relatively short time windows and have not described healthcare utilization or sources of COVID-19 exposure in pregnant women during the pandemic.

At Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system, we conducted a survey among all women who were pregnant at any time during January 2020 to April 2021. The survey was designed to evaluate the frequency of self-reported COVID-19 testing, medical diagnosis, symptoms and related health care utilization. The aims of the present analysis were to a) estimate the crude prevalence of diagnosed COVID-19 and testing frequency for COVID-19 among pregnant women overall and by sociodemographic characteristics, neighborhood factors, and underlying comorbidities, and b) describe frequencies of symptoms, consequent health care utilization, and possible COVID-19 exposures between January 2020 and May 2021.

Methods

Results

Between June 22, 2020 and May 10, 2021, a total of 19,458 of 82,482 eligible women (23.6%) completed the survey, 73.8% while pregnant (of which 92.1% were in their second or third trimester) and 26.2% after delivery (mean [SD]: 10 [7] weeks postpartum). Postpartum respondents were pregnant between March 2019 and April 2021, and the majority (98.3%) gave birth between February 2020, when the first identified cases of COVID-19 were reported in California, and August 2020. The majority of all respondents were in their second trimester (68.9%) and a plurality were 30–34 years old (40.0%), White (47.3%), and living in the lowest quartile of neighborhood deprivation (31.3%) (Table 1).

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Table 1. Characteristics of survey respondents, Kaiser Permanente Northern California.

https://doi.org/10.1371/journal.pone.0256891.t001

In comparison to survey non-respondents, respondents were more likely to be White, ≥30 years old, and live in neighborhoods with low deprivation. The frequency of any history of EHR-documented COVID-19 diagnosis was similar between respondents and non-respondents (2.3% vs. 2.4%, p = 0.60) (S1 Table).

Prevalence of COVID-19 during pregnancy

A total of 494 respondents (2.5%) reported that a healthcare provider told them that they had or likely had COVID-19 during their pregnancy (Table 2). The crude prevalence of self-reported COVID-19 was highest for women <25 years of age (5.1%), Hispanic (4.4%) and Black women (3.1%), and women living in neighborhoods with the highest deprivation (i.e., 4th quartile of NDI) (4.1%) (Table 2). After adjustment for other sociodemographic characteristics, the prevalence of self-reported COVID-19 remained significantly higher among the youngest women (<25 vs. ≥35: adj-PR [95% CI]: 1.75 [1.23–2.49] and 25–29 vs. ≥35: 1.60 [1.26–2.03]), women of Hispanic race/ethnicity compared with White women (adj-PR[95% CI]: 1.81 [1.28–2.55]), women impacted by personal or partner job loss or reduced hours during the pandemic compared with women without impacted employment (adj-PR[95% CI]: 1.23 [1.02–1.47]), and women living in the highest quartile vs. lowest quartile of NDI (adj-PR [95% CI]: 1.74 [1.33–2.27]). Other socioeconomic indicators such as health insurance payer and receipt of food assistance were not significantly associated with self-reported COVID-19 after adjustment for covariates. While the crude prevalence of EHR-documented COVID-19 was lower than self-reported COVID-19 (1.4% vs 2.5%), prevalence patterns by age, race/ethnicity, and NDI were similar for both definitions (Table 2).

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Table 2. Self-reported and EHR-documented COVID-19 prevalence by sociodemographic and clinical factors, crude and adjusted prevalence ratios.

https://doi.org/10.1371/journal.pone.0256891.t002

The crude prevalence of self-reported COVID-19 was highest in women with asthma (3.2%), hypertension (3.5%), and obesity (3.1%) and lowest in women with none of these conditions (2.3%) (Table 2). After adjustment for age, race/ethnicity, and NDI, the prevalence of self-reported COVID-19 did not significantly differ between women with and without these underlying comorbidities (Table 2). Similar patterns were observed for EHR-documented COVID-19, with the exception of a marginally significant higher prevalence of COVID-19 in overweight women compared with normal/underweight women (adj-PR [95% CI]: 1.19 [1.03–1.37]). Obesity, however, was not associated with COVID-19 after adjustment for covariates.

Among survey respondents who were pregnant at the time of survey completion (n = 14,353), 4,630 (32.3%) reported having received a diagnostic test for SARS-CoV-2 during their pregnancy, and among those, 402 (8.7%) reported a positive test result (Table 3). The percentage of women who reported receiving a test was highest in the first trimester of pregnancy (44.9%) and among women of Hispanic (34.9%) and other/missing race/ethnicity (39.1%), women with commercial insurance (33.4%), and women with underlying comorbidities (32.8–39.3%). The frequency of COVID-19 testing was higher among women who completed the survey in 2021 than in 2020. Among women who reported being tested, test positivity was highest for women responding to the survey in late 2020 and early 2021 (9.3–13.2%), the youngest women (<25 years: 20.8%), Black (16.4%) and Hispanic (16.4%) women, women on government insurance (17.8%), women living in neighborhoods in the highest quartile of deprivation (16.8%), and women with obesity (12.4%) or hypertension (12.9%). Among women who reported living with someone who had or likely had COVID-19, 53.8% were tested for COVID-19 with a test positivity frequency of 53.7%.

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Table 3. Frequency of self-reported receipt of COVID-19 test and test-positivity among women who were currently pregnant at time of survey completion.

https://doi.org/10.1371/journal.pone.0256891.t003

Symptoms, consequent healthcare utilization, and potential sources of COVID-19 exposure

Women with diagnosed COVID-19 were more likely to report living with someone who had or probably had COVID-19 (49.6% for self-report, 64.1% for EHR-documented), than women in the no-COVID-19 group (3.2%) (Table 4). Women with diagnosed COVID-19 according to self-report or EHR documentation were more likely than women in the no-COVID-19 group to experience several different symptoms during pregnancy (Table 4), including fever (33.6% and 33.0%, respectively vs. 3.8%), cough (48.0% and 39.1%, respectively vs. 8.0%), headache (56.1% and 55.8%, respectively vs. 22.0%), and fatigue or excessive sleepiness (50.0% and 54.0%, respectively vs. 23.5%). Loss of smell or taste was common among women with COVID-19, occurring in 42.3% of self-reported and 54.0% of EHR-documented COVID-19, compared with 1.2% in the no-COVID-19 group. Approximately 20% of women in either COVID-19 group experienced no symptoms compared with 61% in the no-COVID-19 group.

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Table 4. Self-reported symptoms during pregnancy, consequent healthcare use, and possible sources of COVID-19 exposures in the two weeks before symptoms started.

https://doi.org/10.1371/journal.pone.0256891.t004

Among women who experienced symptoms during pregnancy, those in the self-reported and EHR-documented COVID-19 groups were significantly more likely than those in the no-COVID-19 group to report having had an overnight hospitalization (2.2% and 1.8%, respectively vs. 0%) or an in-person (16.1% and 14.3%, respectively vs. 6.5%) or telehealth visit with their provider (70.7% and 70.5%, respectively vs. 20.2%), self-isolating as a result of their symptoms (75.3% and 76.8%, respectively vs. 15.7%), and having had contact with someone who tested positive (46.7% and 54.9%, respectively vs. 1.3%) or likely had COVID-19 (both 15.2% vs. 1.9%) (Table 4). However, over a third of women with COVID-19 reported not having a known exposure to someone who had or likely had COVID-19.

Discussion

In a large, diverse population of pregnant women during the first year of the COVID-19 pandemic in Northern California, we found that women who were <25 years of age, Hispanic, living in neighborhoods with high deprivation, and who had experienced personal or a partner’s job loss or reduced employment hours had the highest prevalence of diagnosed COVID-19. Over 50% of women with EHR-documented COVID-19 reported loss of smell or taste, although a fifth of women reported feeling no symptoms during their infection. Fewer than 3% of women with diagnosed COVID-19 and symptoms were hospitalized, suggesting that most symptomatic infections were not severe. Over a third of women with diagnosed COVID-19 were not aware of having had exposure to someone who had or likely had COVID-19 in the two weeks before their symptoms started.

The prevalence of COVID-19 in our sample of survey responders is lower than the prevalence in pregnant women reported by studies conducted in clinical settings across the US. These studies differed from ours in that they sampled over shorter time periods and from universal testing programs of hospitalized women admitted for delivery [10–15] or for COVID-19 related symptoms [1, 16]. A prevalence of 15% was reported among women who were admitted for delivery during the early surge of the pandemic in New York City (March 22-April 4, 2020) [15], when New York’s documented prevalence of COVID-19 in the adult population was much higher than in California [29]. During periods of rapid community transmission in the spring of 2020, Texas, Illinois, Massachusetts, and Connecticut observed infection rates of 2.6–8% in pregnant women who were universally screened for COVID-19 at delivery [9, 12–14]. In April and May, before Southern California witnessed summer surges in COVID-19 transmission, only 1% of pregnant women universally screened at delivery at Kaiser Permanente Southern California tested positive for SARS-CoV-2 [11]. The relatively low prevalence reported in both the Southern and Northern California samples may reflect the early success of local public health mitigation efforts at the beginning of the pandemic. However, in our sample, the low prevalence may also reflect the limited testing availability in the early course of the pandemic when KPNC was following CDC recommendations to test only those with severe symptoms or known exposures. Partway through the study’s observation period, KPNC began universal testing for all patients who presented for scheduled cesarean in October 2020 and for all patients in labor and delivery in December 2020. Northern California also experienced a surge in COVID-19 transmission across November 2020-February 2021, reflected in an observable increase in COVID-19 screening and test-positivity among respondents participating in the survey after October 2020.

The prevalence of COVID-19, whether measured by self-report of a diagnosis made by a healthcare provider or a documented diagnosis in the EHR, was generally highest among women <25 years old; Hispanic women; and women who lived in neighborhoods with high deprivation. Analyses of self-reported SARS-CoV-2 testing also indicated sociodemographic disparities in test-positivity rate, despite SARS-CoV-2 testing frequency being relatively similar across sociodemographic groups. A study in the broader KPNC population also found that sociodemographic factors, particularly race/ethnicity, were stronger predictors of SARS-CoV-2 infection but less predictive of SARS-CoV-2 testing use [30]. In other states, younger age [9, 14] and other sociodemographic indicators, including receipt of government health insurance [12, 14], were associated with heightened risk of COVID-19 in pregnant women. Earlier studies conducted in different US healthcare systems also consistently demonstrate that pregnant Black and Hispanic women have higher rates of COVID-19 [2, 9, 12, 14, 17, 20, 31] and are more likely to have severe symptoms leading to hospitalization [1, 17]. These COVID-19-related health disparities further highlight the pandemic’s interaction with pre-existing social determinants of health, employment in essential high-risk sectors, and systemic racial health inequities in the US [32–34].

In our sample, women with underlying asthma, hypertension, and obesity had a slightly higher prevalence of COVID-19 than their counterparts without these conditions, though these differences were not statistically significant after adjustment for covariates. Previous studies based on universal COVID-19 testing of pregnant women at delivery have found that several conditions, including diabetes, chronic lung diseases, cardiovascular disease, and obesity, were associated with increased risk of severe COVID-19 illness [1, 3, 9, 10, 14, 35]. While the relationship between allergy and COVID-19 has not been scrutinized in pregnant women prior to this study, studies in general populations present mixed evidence, suggesting that more research is needed to understand how specific conditions, treatments, and their interactions may shape COVID-19 susceptibility [23, 27]. Though very few women were hospitalized for COVID-19 in our sample, other studies suggest that underlying comorbidities may put pregnant women at increased risk of COVID-19 complications requiring hospitalization [2, 16, 31].

Pregnancy induces several physiological changes, including phases of immunosuppression and altered cardiopulmonary function, that can increase pregnant women’s susceptibility to infectious disease [36] as well as increase frequency of fatigue and headaches. Further, the pro-inflammatory states that naturally occur during the first and third trimesters can exacerbate a woman’s COVID-19 illness, inducing a cytokine storm of acute inflammation that can adversely affect the short and long-term health of the woman and fetus [37]. While COVID-19-like symptoms were prevalent in women without diagnosed COVID-19, most symptoms, including COVID-19 hallmarks such as cough, headache, and loss of smell or taste [22], were markedly more common in women with COVID-19. Previous studies have found that, among hospitalized women with COVID-19, some symptoms, including cough, fever, and myalgia were less common in pregnant than non-pregnant women, in part because universal testing of pregnant women has led to increased detection of mild and asymptomatic cases [2, 3, 38]. Studies in universal testing settings have demonstrated that 65–94% of pregnant women with SARS-CoV-2 infection experience no symptoms [9–13, 15, 18]. In contrast, only 20% of women with recognized SARS-CoV-2 infection were asymptomatic in our sample, likely reflecting the local testing policies in the early months of the pandemic that prioritized those with symptoms and known exposures.

Our study had some notable limitations. Response rates to the survey were relatively low, raising concerns about non-response bias. In addition, sociodemographic factors associated with higher risk of COVID-19 were also found to be associated with survey non-response. Our survey sample was more likely to be aged 30 years or older and more likely to be White relative to the general KPNC population, which is broadly representative of the insured adult population in California [21]. This potential selection bias suggests that the sociodemographic disparities we observed may underestimate disparities in the general population of pregnant women in California and nationally. Though the rates of some co-morbidities such as asthma, pre-existing diabetes, and obesity were similar in our sample to estimates in nationally-representative samples of the pregnant population, our sample was on average older with a higher proportion of women with commercial health insurance than in the national population [39–42].

The strengths of the present study include the examination of both self-reported and EHR-documented COVID-19 from a general population of pregnant women, providing additional insight regarding infection risk, symptoms, consequent healthcare use, and possible exposures beyond what has been described in earlier studies of pregnant women, which predominantly included women admitted to the hospital for delivery or for COVID-19 complications [2, 10–15]. Women who self-reported COVID-19 but who had no documentation of infection in the EHR may have received testing outside of KPNC and not reported their findings to their healthcare provider. Further strengths include the study’s large sample size, diversity across sociodemographic characteristics and stages in pregnancy, and large window of observation over the first year of the pandemic.

In conclusion, while COVID-19 was recognized in a relatively small number of women in our sample overall, our study identified several subgroups that may be particularly vulnerable to infection and observed unique infection-related symptoms during pregnancy, low frequency of hospitalization but high frequency of self-isolation and use of telehealth visits, and a sizable proportion of women with no known exposures to infected contacts before the onset of their symptoms. It will be important to follow the health of these women and their children in future studies.

Supporting information

Acknowledgments

The authors thank Linda Nkemere, Jenna Ritchie, and Maria Massolo for their contributions to launching and maintaining the survey study.

The survey was adapted from the NIH Environmental Influences on Children’s Health Outcomes (ECHO) COVID-19 Questionnaire [2020] developed for the ECHO-wide Cohort Data Collection Protocol.