Introduction

The first case of infection by the SARS-CoV-2 virus (COVID-19) was described in December 2019 in Wuhan, Hubei province, China. Since then, COVID-19 has spread rapidly and globally, and the World Health Organization (WHO) declared it as a pandemic on March 11, 2020 (Zhou et al., 2020).

SARS-CoV-2 virus infection can cause several symptoms, ranging from asymptomatic manifestations or severe symptoms, to acute respiratory syndrome and even death (Z. Wu & McGoogan, 2020). Clinical progression during the pregnancy-puerperal cycle is not fully known.

Pregnancy determines a physiological condition that includes immunological tolerancefor the proper development of the placenta and the fetus. As in Influenza and SARS, respiratory infections can develop unfavorably in pregnant women (Breslin et al., 2020; Hantoushzadeh et al., 2020; Zaigham & Andersson, 2020). Thus, pregnant women have been a high-risk group for COVID-19 infection (“Protocolo de Manejo Clínico Da Covid-19 Na Atenção Especializada,” 2020).

A series of 43 cases of SARS-CoV-2 in pregnant and postpartum women showed that 86% had mild disease, 9.3% severe disease, and 4.7% critical disease (Breslin et al., 2020).

In addition, when comparing the evolution of the disease in pregnant and non-pregnant women, pregnant women were found to be three times more likely to be admitted to an intensive care unit (ICU) due to the severity of the clinical condition (10.5 vs 3.9 per 1000) than non-pregnant women (Zambrano et al., 2020).

A European study using data of patients from four European hospitals corroborated these facts. Personal factors such as age, body mass index (BMI) and other comorbidities were evaluated, observing an increased risk of serious illness during pregnancy, as well as hospitalization, need for oxygen therapy and endotracheal intubation (Badr et al., 2020).

Iranian researchers also observed a rapid deterioration of the clinical condition in infected pregnant women and puerperae. They were the first to report a pregnant woman’s death due to SARS-CoV-2 (Karami et al., 2020). In general, pregnant women progress to a 25% lethality in acute respiratory syndromes (Wong et al., 2004).

Interestingly, a total of 43 pregnant women tested positive for COVID-19 in a series of cases in New York City. Of these, 31% of pregnant women and puerperae who sought care exclusively for obstetric causes were screened positive for COVID-19 symptoms, among which,, one third of COVID-19 positive women were asymptomatic at the time of care (Breslin et al., 2020).

Taking into consideration high complication rates, including mortality, among women in the pregnancy-puerperae cycle with respiratory infections by other coronaviruses (SARS-CoV and MERS-CoV), or the H1N1 influenza virus, concern about SARS-COV-2 infection in this group is justified (Jamieson et al., 2009; Satpathy et al., 2009; Schwartz & Graham, 2020). Also worth mentioning is a study by Hantoushzadeh et al., (2020), in which seven out of nine pregnant women with an acute SARS-CoV-2 disease eventually died.

In addition to the increase in the severity of clinical symptoms during pregnancy, unfavorable obstetric outcomes may also occur. A systematic review and meta-analysis showed an increased risk for preeclampsia, premature birth and stillbirth when comparing pregnant women infected or not by COVID-19. Among pregnant women with the severe form of the disease, in addition to preeclampsia and premature birth, an increase in cases of gestational diabetes and low birth weight can be observed compared to women with mild presentation of disease (Wei et al., 2021).

Evidence for vertical transmission is limited. In a study with nine pregnant women with SARS-CoV-2 infection, samples of amniotic fluid, cord blood and oropharyngeal swabs from neonates were tested during delivery. All the results were negative for COVID-19. Breast milk after the first lactation was also analyzed, which did not identify the presence of the virus (Chen et al., 2020). In view of these facts, it is observed that the intrauterine transmission of SARS-CoV-2 seems to be rare A viral pathogen must cross the placental barrier for an infection to occur, which is facilitated in cases of high viremia, but this is not the case with SARS-CoV-2 infection (Edlow et al., 2020).

A recent study showed clinical, radiological, and laboratory changes with substantial deterioration in the immediate postpartum period, among which we can mention: a worse respiratory condition, D-dimer elevation, increased leukocytes, and C-Reactive Protein, and a significant drop in lymphocytes (Chen et al., 2020; Wu et al., 2020).

In view of the above, it is important for us to elucidate the evolution and outcomes of COVID-19 in the population of pregnant and postpartum women receiving care at the Hospital Municipal de São Bernardo do Campo (HMU-SBC) from March 1 to July 31, 2020—in the early COVID-19 pandemic.

Methods

Study Design

This retrospective cross-sectional study examined the medical records of confirmed or suspected cases of SARS-CoV-2 in pregnant women and puerperae seen at the Emergency Room of the Municipal University Hospital of São Bernardo do Campo in the early months of the COVID-19 pandemic (from March 1 to July 31, 2020). The study was approved by the Institution’s Ethics Committee and the Clinical Research Ethics Committee of the ABC Medical School under Opinion CAAE - 34735220.8.0000.0082.

The cases were categorized according to the World Health Organization (WHO) classification as suspected, probable, and confirmed (World Health Organization (WHO), 2020).

Women with confirmed or suspected COVID-19 cases from the hospital’s Emergency Room were identified through notification forms. Then, patients’ electronic medical records of the MV-PEP system were reviewed for data collection. Women under 18 were excluded.

Collected Data

The following personal, clinical, and laboratory data of women and their newborns were collected through the review of medical records of the Municipal University Hospital of São Bernardo do Campo of MV-PEP electronic system:

  • General: age, race, schooling, marital status, and tobacco use.

  • Health during pregnancy: number of pregnancies and parity, number of prenatal visits, gestational age, pre-gestational nutritional condition assessed using the body mass index (weight (kg)/height m2), diseases during pregnancy (high blood pressure, diabetes mellitus, genitourinary infections, congenital infections, and asthma).

  • Information on COVID-19 infection: diagnosis type, presence or absence of symptoms such as fever, cough, myalgia, dyspnea, and taste/smell loss. We also considered information about the first visit to the emergency room and the severity such as tachycardia higher than 100 bpm, tachypnea higher than 24 ripm, body temperature equal to or greater than 37.8 °C, and oxygen saturation below 94%.

  • Supplementary exams: information on the COVID-19 diagnostic tests, the blood count, and inflammatory tests was obtained from the medical records, among them, the presence or absence of lymphopenia (value < 1200 cells/mm3), thrombocytopenia (platelets < 150,000) and increased fibrinogen (> 400 mg/dL), lactate dehydrogenase (LDH, > 250 IU/L), aspartate aminotransferase (AST, > 40 U/L) and D-dimer (> 500 ng/mL).

  • Delivery and newborn conditions: delivery type; newborn’s anthropometry (weight, length, and head circumference), used for classification as small, adequate, and large for gestational age, and Apgar in the first and fifth minutes (Villar et al., 2014).

The indication for cesarean delivery was classified as altered fetal parameters, obstetric disease, or elective. Altered fetal parameters were considered indications for fetal tachycardia, non-tranquilizing cardiotocography, fetal macrosomia, restricted growth, fetal malformations, and fetal death. The reasons for obstetric pathology included cases of oligo- and polyhydramnios, pre-eclampsia, premature rupture of ovular membranes, respiratory failure, and premature labor. Repetitiveness, transverse presentation, and unfavorable cervix for induction were included in elective cases. These parameters were included in the analysis to better understand the impact of influenza syndrome and its outcomes among postpartum women.

Considering the WHO diagnostic categorization criteria, COVID-19 diagnosis was considered confirmed in positive RT-PCR SARS-CoV-2 diagnostic or serological tests (Zalzala, 2020). Those with suspected pulmonary radiological alteration, agenesis, or anosmia without a laboratory-confirmed diagnosis were considered a probable diagnosis, and those with only acute fever and cough symptoms were considered as suspected.

Inclusion and Exclusion Criteria

The inclusion criteria were:

  • Pregnant women, parturients or postpartum women (from two hours postpartum to 42 days);

  • Age between 18 and 50 years;

  • Having flu-like symptoms or a positive COVID-19 test (RT-PCR or serology);

  • Enrolled in the HMU-SBC.

  • The exclusion criteria were:

  • Not having performed RT-PCR SARS-CoV-2 or serology for COVID-19 detection.

  • Age under 18 years.

Pregnant women presenting with any of the following signs/symptoms were diagnosed as having (considered to have) the flu syndrome: fever, cough, asthenia, anorexia, myalgia, difficulty breathing, sputum production, nasal or conjunctival discharge, difficulty swallowing, sore throat, runny nose, signs of cyanosis, flaring of the nose, loss of taste and/or smell, diarrhea, dyspnoea.

Statistical Analysis

The numerical variables were processed by mean and standard deviation, and the qualitative variables as absolute numbers and percentages. The comparison between the groups of pregnant women with and without symptoms and who required hospitalization or not was performed using the t-Student test when the distribution was normal and using the Mann–Whitney test when it was not. The Chi-square test or Fisher’s exact test was used for comparative assessment of qualitative variables. We performed a binary logistic regression of qualitative variables that were significant when comparing pregnant women who required hospitalization with those who did not. Data were tabulated in the Excel system, and the Stata version 11.0 program was used for all statistical analyses, considering p < 0.05.

Results

In the period established for the study, 6,005 women were attended to in the obstetric emergency room, out of which 219 were identified and we identified 219 women with a confirmed or suspected diagnosis of SARS-CoV-2. Of these, 64 (29%) were asymptomatic. Table 1 shows the description and comparison of maternal and newborn characteristics according to the presence or absence of symptoms. The mean gestational age at delivery, anthropometric measurements, and Apgar values of newborns were similar in women who showed flu-like symptoms or not. Asymptomatic women were younger and had a higher number of prenatal visits. Obesity was the most prevalent associated disease (26.1%), followed by hypertensive syndrome (17.4%), asthma (7.3%), and diabetes mellitus (6.0%). Thirty-five percent of women who had some flu-like symptoms required hospitalization, and of these, 6% were referred to the ICU at some point. Fever was identified in 15.5% of women evaluated in the emergency room, followed by tachycardia, which was found in 11% of women. The serological test was positive in 51% of the women evaluated, the RT-PCR test for SARS-CoV-2 in 31% of them, and while 7% had a probable diagnosis, 11% were suspected cases.

Table 1 Description and comparison of maternal and newborn characteristics according to the presence or absence of symptoms
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Fever was reported by 36% of the patients, followed by cough (27.5%), myalgia (27.5%), smell loss (23%), taste loss (22.5%), and dyspnea (21.5%). The cesarean delivery by fetal or maternal indication was more frequent in women who showed symptoms mainly due to obstetric diseases, with 27.5% in symptomatic and 19% in non-symptomatic. These data can be seen in Table 2.

Table 2 Description and comparison of the referred symptoms and laboratory tests performed according to the presence or not of flu-like symptoms
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Fifty-three women (24.5%) of the total study population required hospitalization due to clinical symptoms probably related to COVID-19. Newborn and maternal characteristics of the hospitalized women can be seen in Table 3. The most common symptoms for the women in the emergency room was fever (39.6%), followed by tachypnea (11.3%), oxygen saturation below 94% (11.3%), and tachycardia (7.5%). Compared with women who did not require hospitalization, there was no difference in age, number of pregnancies and prenatal care visits, gestational age at delivery, and Apgar score in the first and fifth minutes. However, they had newborns with lower birth weight (p < 0.01), shorter length (p = 0.02), and smaller head circumference (p = 0.03). When assessing associated diseases, 39.5% of women with hypertensive syndrome, 29% with obesity, 11.5% with gestational diabetes, and 9.5% of asthmatics required hospitalization.

Table 3 Description and comparison of maternal and newborn characteristics according to pregnant women’s hospitalization need due to suspected COVID-19
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Hospitalized women due to suspected COVID-19 referred more symptoms and had more altered laboratory tests when compared with not hospitalized women. This can be seen in Table 4. The symptoms were myalgia (p = 0.03), dyspnea (p < 0.01), taste loss (p < 0.01) and smell loss (p < 0.01). The abnormal laboratory tests were lymphopenia (p < 0.01), thrombocytopenia (p < 0.01), increased LDH (p < 0.01), increased AST (p < 0.01), increased D-dimer (p < 0.01), increased fibrinogen (p < 0.01), need for ventilatory support (p < 0.01), and need for oxygen catheter (p < 0.01).

Table 4 Description and comparison of the referred symptoms and laboratory tests of the population according to whether they required admission due to suspected COVID-19
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Table 5 shows that hospitalized women were seven times more likely to have a fever in the emergency room than those who were not hospitalized (OR = 7.6, 95% CI 3.48–16.9). Hospitalized women were 3.3 times more likely to show smell loss (OR = 3.3, 95% CI 1.66–6.5) and 2.9 times more likely to show taste loss (OR = 2.9, 95% CI 1.4–5.7) than those who were not.

Table 5 Binary logistic regression for the likelihood of hospitalization due to COVID-19 according to the presence or absence of hypertensive syndrome, tachypnea, fever, myalgia, dyspnea, and taste/smell loss
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Discussion

Pregnant women with a suspected or confirmed COVID-19 diagnosis, regardless of clinical symptoms, did not show, on average, unfavorable perinatal or neonatal outcomes. Nevertheless, pregnant women with worse clinical outcomes progress, who required hospitalization, had a higher rate of cesarean deliveries and newborns with smaller anthropometric measurements than those who did not.

Approximately 29% of the pregnant women included in the study did not report any symptoms, most of whom were diagnosed by serological examination and some by RT-PCR for SARS-CoV-2. In an observational cohort study, Salvatore et al. (2020) observed that 26% of pregnant women diagnosed with COVID-19 were asymptomatic.

Vaginal delivery was the primary childbirth method in the population studied. However, cesarean delivery was more frequent in symptomatic women and in those requiring hospitalization due to COVID-19. Among those who underwent cesarean section, surgical indications for obstetric pathology were more frequent in the symptomatic women, whereas elective indications were more common in the asymptomatic ones. Systematic reviews show that most studies report cesarean delivery as the main route (Castro et al., 2020; Zaigham & Andersson, 2020). An observational cohort study that evaluated 116 pregnant women diagnosed with COVID-19 showed a higher number of vaginal deliveries (Salvatore et al., 2020). Except for pregnant women with an unsatisfactory clinical progress, COVID-19 diagnosis is not an influencing factor in choosing the delivery method.

Similarly to what has been reported in the literature, the main clinical symptom reported by pregnant women was fever, followed by cough, myalgia, taste loss, smell loss, and dyspnea (Castro et al., 2020; Zaigham & Andersson, 2020). Of the symptoms evaluated in the emergency room, fever was also the most frequent, followed by tachycardia and tachypnea. However, when comparing women who needed hospitalization or not, the presence of tachycardia measured in the emergency room was higher in those who did not hospitalize. Pregnant women who required hospitalization had a higher percentage of myalgia, dyspnea, taste loss, smell loss, and lymphopenia than those who did not.

The presence or absence of high blood pressure, diabetes, obesity, and asthma was similar when comparing symptomatic and non-symptomatic women. On the other hand, women presenting with hypertension (39.5%) were more likely to be hospitalized than those presenting without (13.9%), compared with women with and without hypertension who did not need hospitalization. Although it was not a risk factor for hospitalization, similarly to what occurs in the general population, it was a risk factor for worse clinical progress of pregnant women (Narang et al., 2020).

In the comparative evaluation among women who required hospitalization or not due to COVID-19 infection, we observed that the former gave birth to newborns with a lower mean value of body weight, length, and head circumference. Birth weight below 2500 g was also more prevalent in these women. It is essential to mention that the gestational age of delivery was compatible with the term and similar in both populations. This result is similar to the observational cohort study of newborns from mothers infected with SARS-CoV-2, in which more than 80% of births took place at 37 weeks, and more than 90% of newborns were born weighing more than 2500 g (Salvatore et al., 2020).

In an Irish study, the effect of COVID-19 on fetal growth was analyzed and 5.3% of babies born to mothers diagnosed with SARS-CoV-2 were small for gestational age (SGA). The study showed a tendency towards a lower birth weight in these women, excluding asymptomatic mothers at the time of screening (Murphy et al., 2021).

Additionally, high rates of low birth weight (< 2500 g) in infants of infected mothers have been described in some studies (7.8–47.4%), although this is confounded by a high incidence of preterm delivery (Papapanou et al., 2021).

According to the WHO COVID-19 classification, most of our case studies were confirmed and 18% were probable or suspected COVID-19 cases. The diagnosis of asymptomatic pregnant women was confirmed by serology, and RT-PCR SARS-CoV-2 confirmed symptomatic women’s diagnosis. We could not establish a correlation between the time of collection and symptoms in cases with a serological diagnosis. It is interesting to note that 27% of hospitalized pregnant women had a probable or suspected diagnosis.

The main factor influencing the hospitalization of patients was fever above 37.8 °C in the emergency room, and hospitalized women were seven times more likely to have fever than those who were not hospitalized, and having a taste and smell loss increased the likelihood of hospitalization. This result is explained by the fact that fever in pregnant women is usually a criterion for hospitalization, and the other symptoms are specific manifestations of COVID-19 infection.

Compared to previous studies that evaluated the impact of COVID-19 infection on pregnant women, the advantages of this study are the high number of pregnant women evaluated and the fact that they were all treated in the same hospital. This facility is the main women’s health care reference center of this Municipality. On the other hand, this is a retrospective study reviewing medical records influenced by the lack of information, impossibility of verifying facts, knowledge of the moment, or circumstances in which the diagnostic tests and the severity of referred symptoms were collected. In addition, it is worth remembering that serology collections for the diagnosis of COVID-19 were performed at a time when vaccines for the disease did not exist and many diagnoses were still made using this method., With the implementation of vaccines, however, this changed. Currently, RT-PCR is considered the gold standard for diagnosing the disease (Iro et al., 2022). Some studies cite that to avoid false-negative results, a combination of RT-PCR with the patient's clinical condition, radiological or serological tests can be performed to screen patients at high risk of being infected with SARS-CoV-2 (Dardenne et al., 2022).

Conclusion

Targeted assessment is vital for early detection of COVID-19 in a pregnant woman. Health care professionals should, therefore, be trained in recognizing signs and symptoms of COVID-19, thereby avoiding hospitalization in this group of patients. Studies indicated that perinatal outcome of women who were hospitalized by COVID-19 showed higher rates of cesarean deliveries, and newborn babies were found to have low anthropometric measurements.