Impact of SARS-CoV-2 infection and vaccination on cesarean section outcomes: a retrospective analysis

Setting

The study design received approval from the hospital’s ethics committee on December 22, 2022, and was designed in line with the principles of the Declaration of Helsinki. The research was carried out at a tertiary referral state hospital, encompassing data from the first COVID-19 PCR-positive cesarean section performed in October 2020 to the latest cesarean section conducted in July 2022. Data retrieval and clinical follow-up records were conducted from the hospital’s digital archive and supplemented by public health surveillance data.

Participants

A total of 297 individuals who underwent cesarean section at our hospital were included in the study cohort. Following our clinical protocol during pandemics, instead of routine screening of all patients upon admission, individuals displaying symptoms of COVID-19 infection or who had recent close contact with confirmed cases, or lived with a quarantined individual, underwent nasopharyngeal swab rapid antigen PCR testing for SARS-CoV-2 and variant status. Thus, inclusion criteria encompassed individuals with positive COVID-19 PCR testing results. Exclusion criteria included those with negative PCR testing but positive findings on chest computed tomography (CT).

The management of pregnant women with symptomatic respiratory infections due to COVID-19 was carried out through a multidisciplinary approach. Hospital admission criteria included moderate to severe disease, mild disease with comorbidities, and obstetric risks. Uncomplicated COVID-19 cases were monitored without antiviral treatment, while antiviral therapy was considered for more severe cases based on the risk-benefit ratio. Radiological imaging was performed with abdominal shielding if respiratory distress was present. Antibiotics were given for suspected bacterial pneumonia, and empirical treatment for influenza was administered if needed. Fetal lung maturation was induced with betamethasone or dexamethasone between 24-34 weeks. High-dose steroids were transitioned to prednisolone or hydrocortisone after lung maturation. Magnesium sulfate for neonatal neuroprotection was decided in consultation with a perinatologist. Anti-cytokine therapy was used for macrophage activation syndrome in life-threatening cases, and a multidisciplinary approach was adopted for ARDS. Delivery timing was determined based on obstetric indications, disease severity, maternal condition, comorbidities, gestational age, and fetal well-being. Cesarean delivery was performed for rapid clinical deterioration, acute organ failure, septic shock, mechanical ventilation difficulties, and fetal distress. Postpartum analgesia was provided with acetaminophen, and venous thromboembolism prophylaxis was administered with low molecular weight heparin. Depending on the maternal clinical condition, continuous or frequent electronic fetal monitoring and biophysical profile assessments, including ultrasonography and/or Doppler studies, were conducted to monitor fetal well-being in cases of maternal desaturation or assessed fetal intrapartum compromise risk factors.²⁰

Variables

Key variables examined in the study included maternal and gestational age, vaccination and variant strains, indications for surgery, maternal complications (acute respiratory distress syndrome [ARDS], mortality), neonatal outcomes (APGAR scores, fetal distress), ICU admission, and the overall monthly number of cesarean sections performed during the study period. These variables were analyzed to determine the mortality rate of SARS-CoV-2 before 31 August 2021, and after 1 September 2021, marking the beginning of nationwide vaccination of pregnant individuals. Additionally, the late post-vaccination period specifically refers to the timeframe aligned with 70% of the median immunization coverage range nationwide at 2 September 2021.^17,18

Data sources/measurement

Data were extracted from electronic medical records, encompassing demographic information, clinical history, and outcomes. COVID-19 vaccination status and variant strains were documented based on patient records and supplemented by public health surveillance data. Maternal and neonatal outcomes were categorized based on clinical management protocols established during the pandemic, with periodic updates in response to evolving evidence and guidelines.²⁰

Bias

Potential sources of bias in this retrospective study include the reliance on hospital records and public health data, which may be subject to documentation errors. Efforts to mitigate potential sources of bias included excluding individuals with negative PCR testing but positive findings on chest CT scans to ensure a more objective cohort.

Study size

The study included PCR-positive COVID-19 cesarean sections conducted within the study period, spanning from the beginning of the pandemic. Given the observational nature of the study, a power calculation was not conducted.

Mortality data of COVID-19 PCR-positive patients

Table 2 offers insights into the mortality outcomes of COVID-19 PCR-positive patients undergoing cesarean sections during pre-vaccination and post-vaccination periods. In the pre-vaccination group, a total of 13 mortalities (8.1%) were observed, compared to 9 mortalities (6.6%) in the post-vaccination group (P=.610). Although, there was no significant difference in the mean age of patients, gravidity, parity numbers, or the presence of additional chronic diseases between the two cohorts, notabibly differences in maternal complications were observed. Maternal ARDS was noted in 46.2% (n=6) of mortalities in the pre-vaccination group compared to 11.1% (n=1) in the post-vaccination group (P=.045). Among the entire mortality cohort of COVID-19 PCR-positive patients, 2 Delta variants (15.4%) were observed in the pre-vaccination group. None of the mortalities were vaccinated, and all deaths occurred during ICU admission after the cesarean section operation.

Variant and vaccinated patient data of COVID-19 PCR-positive patients

Table 3 presents variant data, vaccinated patients data of COVID-19 PCR-positive patients undergoing cesarean sections. The Delta variant was the most prevalent, accounting for 5 cases, followed by the Omicron and English variants with 1 case each. Patients infected with the Delta variant exhibited a higher incidence of ICU admission of 4 patients (80%) and mortality of 2 patients (40%) compared to those infected with other variants. Additionally, 2 Delta PCR-positive patients (40%) experienced severe maternal complications such as ARDS. The single patient with the Omicron variant also required ICU admission but had no mortality, indicating that Omicron can still lead to severe outcomes. Conversely, the patient with the English variant did not require ICU admission and had no mortality, observed less severe outcomes compared to Delta and Omicron. Notably, among the 12 vaccinated patients, none required ICU admission or experienced mortality, regardless of the type of vaccine or doses administered. Among vaccinated patients, 11 patients (91.6%) were fully vaccinated, having received two or more doses.¹⁸

Future directions and recommendations

It is crucial to highlight the significance of COVID-19 vaccination for pregnant individuals within the broader context of global vaccination efforts. Pregnant individuals face heightened risks associated with COVID-19 infection, including severe illness and pregnancy complications. The risk of maternal mortality can be as much as thirty times higher compared to the general population, with increased rates of cesarean delivery, neonatal care unit admissions and stillbirth rates particularly in low- and middle-income countries, highlighting the critical need for access to high-quality maternity care. These adverse outcomes underscore the importance of vaccination in this population.^34-37

In line with updated recommendation on 5 December 2023 from WHO, priority groups for COVID-19 vaccination include pregnant individuals, along with older adults, immunocompromised individuals, healthcare workers, and children above six months of age.³⁸ These priority groups are recommended to receive both primary vaccination series and booster doses, with intervals between doses as per guidelines.

In line with CDC recommendations on 12 September 2023, COVID-19 vaccination during pregnancy is strongly advised due to the heightened risk of severe illness from COVID-19 in pregnant individuals. Additionally, recent WHO guidance on 13 December 2023 underscores the broad cross-reactive neutralizing antibody responses elicited by monovalent XBB.1.5 COVID-19 vaccines against circulating variants, emphasizing the importance of vaccination in protecting against evolving strains of the virus. Furthermore, CDC recommendations for updated COVID-19 vaccines highlight the critical role of vaccination in mitigating the potentially serious outcomes of COVID-19 illness during pregnancy.^38-41

In a study of 196 470 pregnancies in Sweden and Norway, where 48% of pregnant women had been vaccinated, there was no increase in the odds of adverse neonatal outcomes.⁴² However, further studies are crucial to evaluate the effects of newly developed COVID-19 vaccines developed on various platforms on SARS-CoV-2 variants and VOCs, particularly in community-based populations that include pregnant individuals.

In conclusion, in light of the evolving epidemiology of COVID-19 and the emergence of new variants, ongoing surveillance efforts are crucial to inform future vaccination strategies and effectively control the pandemic. Research endeavors aimed at understanding the immune response to variant strains and advancing the development of next-generation vaccines play a pivotal role in mitigating the enduring impact of SARS-CoV-2 infection. Additionally, integrating COVID-19 vaccination with existing influenza vaccination programs, including extension to pregnant individuals, holds promise in maximizing vaccine coverage and providing comprehensive protection, particularly among vulnerable populations like older adults.⁴³ While significant immunity to SARS-CoV-2 suggests the conclusion of the pandemic’s acute phase, COVID-19 persists as a global threat and endemic, particularly in regions with inadequate vaccine coverage and public health systems. Outbreaks persist, and the threat of variant strains remains a concern.