Human immunity is closely aligned with the circadian rhythm. During sleep, levels of circulating leukocytes, monocytes, and lymphocytes decrease due to their redistribution to the lymphoid system [1]. Sleep also promotes the proliferation of lymphocytes and natural killer (NK) cells. Furthermore, sleep increases the production of proinflammatory cytokines including interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, while reducing IL-10 levels, thereby shifting the T helper (Th) 1/Th2 balance toward a Th1 response [2]. Moreover, the formation of immunological memory shares a similar process with the central nervous system, which is divided into three stages. In the encoding phase, information is absorbed as pathogens are engulfed and broken down by antigen-presenting cells (APCs). During consolidation, this information is transferred to long-term storage by APCs to T lymphocytes. In the recall phase, remembered information is retrieved through the activation of memory T and B lymphocytes. Sleep, especially slow-wave sleep, is crucial for enhancing memory consolidation in both systems [3].

Rotating night shift (RNS) work may disrupt the circadian rhythm and lead to numerous health problems, including cardiovascular disease, metabolic disease, cancer, and immune abnormalities. Roughly, it affects 10 % to 30 % of employees worldwide [4], with even higher percentages observed in specific sectors such as manufacturing, healthcare, retail, service, and transportation. Previous studies have demonstrated that night shift work induces low-grade inflammation by elevating IL-6, TNF-α, and C-reactive protein (CRP) [[5], [6], [7]]. Loef B. and coworkers reported that chronic exposure to night shift work may lead to a higher monocyte count (1.15 fold increase), while recent exposure results in a higher mean number of lymphocytes, T cells, and cytotoxic T cells [8]. Research has also demonstrated that night shift workers are more vulnerable to infections [9,10]. Early literature has documented that insufficient sleep (either through restriction or total loss) following vaccination dampens the formation of antigen-specific T helpers and antibodies [11,12]. A human observational study further suggested that shorter sleep time prior to influenza vaccination negatively affects antibody responses to viruses [13]. Night shift workers experiencing short and irregular sleep may dampen the formation of immunological memory and impair the effectiveness of vaccinations [6,14].

Since 2019, the coronavirus SARS-CoV-2 has spread worldwide, causing billions of confirmed cases and millions of deaths. To combat this devastating pandemic, various strategies have been implemented, including frequent surface cleaning, the use of personal protective equipment, improved ventilation, and, most importantly, the building of population immunity through extensive vaccination. Various vaccinations have been developed during the pandemic, and most suggested administering 2 doses to achieve promising efficacy [15]. Generating a better immune response to SARS-CoV-2 is another issue. It has been demonstrated that heterologous vaccination and being boost-vaccinated after natural infection can elicit higher antibody titers [16]. Different types of shift work also affect the prevalence of COVID-19 infection and vaccination responses [[17], [18], [19]]. Although the COVID-19 pandemic has come to an end and the CDC COVID-19 Vaccination Program has concluded, the experiences gained from the pandemic may apply to other infections.

The present cross-sectional study aims to study the impact of shift work type on immune homeostasis and vaccination in hospital workers during the COVID-19 pandemic. Our study revealed that RNS work might induce low-grade inflammation and shift the Th1/Th2 balance toward Th1. RNS workers exhibited lower anti-S1 IgG levels at 3 to 6 months after COVID-19 antigen exposure compared to day shift (DS) workers. Decreased proportions of circulating naïve B, and NKT cells, and increased proportions of T cell subsets, were observed in the RNS group. Moreover, the anti-S1 IgG titers presented a significant positive correlation with the expression of NKT cells, indicating that RNS work could alter immune homeostasis and potentially lead to the reduction of lasting anti-S1 IgG levels following COVID-19 antigen exposure.