Tumor necrosis factor alpha (TNFα) is a major infection-stimulated cytokine involved in the pathophysiological development of not only autoimmune diseases, but also negative pregnancy outcomes, such as miscarriage and preterm labor (Hunt et al., 1996, Brogin Moreli et al., 2012). TNFα inhibitors (TNFαi) is a group of recombinant biologic agents that neutralize human TNFα and provides treatment to diseases including Crohn’s disease and moderate to severe active rheumatoid arthritis. Studies have shown that certain group of patients with recurrent pregnancy failure may also benefit from preconceptional and antenatal use of TNFαi (Zhong et al. 2022).

SARS-CoV-2 infection has been worldwide headache for the past 3 years. Epidemiological waves of COVID-19 with substantial proportion of reinfection cases continued to be reported frequently (West et al., 2021, Wang et al., 2021). There have been raised concerns on the safety of TNFαi in the complex context of pregnancy in the COVID-19 pandemics. On one hand, the information of safety in pregnancy is limited for this relatively young drug group (Flint et al. 2016). On the other hand, the immunosuppressive nature of TNFαi, in addition to the unique gestational immune and angiogenic status lead to hesitation in its use (Palomo et al. 2022).

Starting from 5th December 2022, Mainland China eased its COVID-19 prevention and control policy and ended the dynamic zero-COVID strategy. As the majority of our population in Mainland China were never infected with COVID-19, all patients were highly susceptible. Positive nucleic acid amplification tests (NAATs) in Zhejiang province increased from hundreds in the month of November 2022 to a peak of 1 to 2 million per day in December 2022, and all were Omicron variants (COVID-19 Clinical and Surveillance Data — December 9, 2022 to January 23, 2023, China). It was estimated that 82.4% of individuals had been infected as of 7th Feb 2023, the vast majority of which were primary infection (Di Fu et al. 2023).

In this study, we looked into this particular two-month window, and analyzed patients receiving TNFαi, with an emphasis on pregnancy, aiming to provide real world data on the safety and efficacy of TNFαi use in pregnancy in the context of COVID-19 pandemic.