Increased COVID-19 Severity among Pregnant Patients Infected with SARS-CoV-2 Delta Variant, France

We conducted a retrospective study of pregnant persons hospitalized for severe acute respiratory syndrome coronavirus 2 infection in France. Delta variant infection had a relative risk of 14.33 for intensive care unit admission and 9.56 for high supplemental oxygen support. The Delta variant might cause more severe illness during pregnancy.

We conducted a retrospective study on all hospitalized pregnant women diagnosed with COVID-19 by reverse transcription PCR of nasopharyngeal swab samples during March 1, 2020-November 15, 2021. We defined severe COVID-19 as a case requiring intensive care unit (ICU) admission and critical COVID-19 as a case in the ICU that required high supplemental oxygen support, either high-flow nasal cannula, noninvasive ventilation, or mechanical ventilation.
To compare the frequency of severe and critical COVID-19 among the 3 periods, we calculated the ratio of women of reproductive age (defined as 15-42 years) hospitalized with COVID-19 during the same period. During March 1, 2020-November 15, 2021, a total of 77 women of reproductive age were hospitalized for COVID-19 in our facility, including 30 pregnant women (Figure). Among the 30 pregnant persons, 7 were transferred to the ICU (1 confirmed Alpha variant, 6 confirmed Delta variant

RESEARCH LETTERS
We conducted a retrospective study of pregnant persons hospitalized for severe acute respiratory syndrome coronavirus 2 infection in France. Delta variant infection had a relative risk of 14.33 for intensive care unit admission and 9.56 for high supplemental oxygen support. The Delta variant might cause more severe illness during pregnancy.
The risk ratios for severe and critical COVID-19 during the 3 periods rebut the hypothesis that the increasing number of SARS-CoV-2 infections in younger persons, combined with low acceptance for COVID-19 vaccination during pregnancy, sufficiently explain the increased risk for severe disease noticed with the Delta variant (5). SARS-CoV-2 lineage B.1.617 (Delta) probably is associated with increased COVID-19 severity among pregnant persons compared with previous variants (2,6). This consistent difference suggests a change in pathogenicity in pregnant persons and requires further investigation. A large retrospective cohort study comparing similar groups of pregnant women with COVID-19 during the pre-Delta period (n = 224) and the Delta period (n = 69) suggested an increase in critical illness and adverse perinatal outcomes associated with the Delta variant during pregnancy (7). Another study showed that pregnant patients infected with the Delta variant were more symptomatic and were diagnosed earlier than patients diagnosed before Delta was prevalent (8). Our results support the possibility of increased COVID-19 severity with Delta compared with previous SARS-CoV-2 variants.
Our study's first limitation is that standard care and hospitalization criteria changed between the 3 periods, which could have affected our results. We suspect thresholds for ICU admission were lower for pregnant persons during periods 2 and 3 than during period 1 because of a partial ICU bed saturation during the first COVID-19 wave (9). COVID-19 treatment progressively improved and standard care was more optimal during periods 2 and 3 than period 1(Appendix, https:// wwwnc.cdc.gov/EID/article/28/5/21-2080-App1. pdf); thus, we should have expected fewer severe and critical COVID-19 patients in periods 2 and 3, but we observed the opposite. The main limitation of our study is the small sample size in a monocentric study, which prevents us from issuing any conclusions.
Despite the small number of cases, our findings on COVID-19 severity among pregnant persons infected with the Delta variant are consistent with those of other studies (2,(6)(7)(8). A larger national cohort study, such as the one conducted by the UK Obstetric Surveillance System (N. Vousden et al., unpub. data, https://www.medrxiv.org/content/10.1101/2021.0 7.22.21261000v1), could confirm our findings. Nonetheless, our results show that SARS-CoV-2 prevention measures, especially COVID-19 vaccination, are needed during pregnancy.
T he B.1.1.529 (Omicron) variant of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries a high number of nonsynonymous mutations in the spike glycoprotein, relative to that of the ancestral (wild-type) strain (Wu01). Those mutations result in a strong immune evasion phenotype, as demonstrated by severely reduced serum neutralization after vaccination or previous infection with ancestral variants in most persons (1)(2)(3), lower vaccine effectiveness, and increased rates of reinfection (N. Andrews et al., unpub. data, https://www.medrxiv.org/content/10.1101/2021. 12.14.21267615v1). However, booster vaccinations with 1 dose of mRNA vaccine after priming with an initial 2 doses induce high levels of serum neutralizing activity against Omicron (1,4). Substantial efforts have therefore been made to speed up booster vaccination campaigns in light of the rapid spread of Omicron and the recent surge of infections worldwide. Breakthrough infections after 2-dose mRNA vaccination can result in a natural boost to humoral immunity against SARS-CoV-2 (5; L.J. Abu-Raddad et al., unpub. data, https://www. medrxiv.org/content/10.1101/2022.01.18.2226945 2v2), and emerging evidence suggests that breakthrough infections with non-Omicron SARS-CoV-2 variants also elicit cross-neutralizing serum activity against Omicron (6).