Omicron variant is a relatively mild form of SARS-CoV-2 infection.

Fever and diarrhea are two independent factors for severe Omicron infection.

Higher symptom score is related to longer VST and LOS.

Since a cluster of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified in Wuhan, China in December 2019, and subsequent worldwide spread, it has caused the coronavirus disease (COVID-19) pandemic. At the time of writing, more than 761 million cases and more than 6.8 million deaths have been reported worldwide (WHO, 2023).

Currently, SARS-CoV-2 has spread globally as an Omicron variant. This variant is heavily mutated, highly contagious and has been designated as a variant of concern (VOC) by the World Health Organization (WHO) (CDC,; Gao et al., 2022). Studies have shown that Omicron variant has reduced pulmonary pathogenicity, milder spectrum of symptoms, and lower severity and mortality compared with previous VOCs (Ye et al., 2022). Here, we report a retrospective study from a Fangcang hospital during the Omicron outbreak in Shanghai, with BA.2 and BA.2.2 sublineage as the predominant variants (Zhang et al., 2022).

Fangcang hospitals are basic medical facilities transformed from large public places such as schools and exhibition centers. They can provide adequate medical services for mild and moderate patients, and prevent further spread of the virus (Chen et al., 2020). Patients who are confirmed to be positive for COVID-19 but have no symptoms or mild symptoms will be quarantined at Fangcang hospital and receive simple treatment. If the patient’s condition get worse, he or she will be transferred to appropriate hospital for further treatment. This can not only save medical resources, provide medical security for as many people as possible, but also effectively stop the spread of the virus.

Thus, the purpose of this study was to: 1) explore risk factors in the development of severe disease in Omicron-infected patients hospitalized in Fangcang hospital; 2) explore risk factors for prolonged viral shedding time (VST) and length of hospital stay (LOS) among non-severe patients using the clinical data collected from a Fangcang hospital in Shanghai.

Over the past three years, Fangcang hospital has been successfully adopted to rapidly contain several waves of SARS-CoV-2 in China, and has been adopted as a core strategy to achieve “dynamic zero”. Since the Omicron outbreak in Shanghai in March 2022, more than 100 Fangcang hospitals have been established to reduce COVID-19 cases as quickly as possible at the lowest cost, making a paramount contribution to the total reopening of Shanghai on June 1, 2022. At present, with the optimization of the COVID-19 control strategy in China, home quarantine is gradually replacing large Fangcang hospitals as the main epidemic prevention measure, and big data like this study is no longer easy to obtain.

People infected with Omicron are relatively mildly ill compared to previous COVID-19 infections (Ye et al., 2022). 25,182 patients from this cohort only shows 39 severe cases (0.2%) and 1 death (0.004%), which is significantly lower than that in Wuhan Fangcang hospitals (Sun et al., 2021). Even among non-severe patients, the average hospital stay is only 6.5 days, which is also much lower than the 10-16 days of Wuhan Fangcang hospitals (Wu S. et al., 2020; Liu et al., 2021), indicating that this wave of Omicron infection is generally milder than the original strain. The clinical characteristics of the same population are described in more detail in another paper (Ying-Hao et al., 2022).

Chronic diseases such as diabetes, and hypertension account for a higher proportion in severe and dead cases of COVID-19 (Wu and McGoogan, 2020). However, the impact of these two common comorbidities on prognosis remains controversial. Several studies have proposed hypertension and diabetes as risk factors for disease severity and mortality (Apicella et al., 2020; Guan et al., 2020; Kabia et al., 2022), and the underlying mechanisms may be related to suppression of immune function of macrophages and lymphocytes (Wu S. et al., 2020; Xu et al., 2020), as well as triggering of acute metabolic complications (Guo et al., 2020). The results of this trial do, however, align with studies showing that preexisting hypertension and diabetes have no effect on severity or mortality in COVID-19 patients (Yang et al., 2020; McFarlane et al., 2022), which may be related to our appropriate exclusion of major confounders such as age, or to Omicron’s relative mildness. In short, this finding has important public health implications for avoiding unnecessary panic caused by the constant mention of diabetes and hypertension as major risk factors for serious illness or death.

As the main finding of this study, we draw a conclusion that gastrointestinal symptom diarrhea is an independent risk factor for clinical deterioration. Evidence suggest that COVID-19 may be transmitted via the fecal-oral route (Xiao et al., 2020). Viruses enter cells by binding to the angiotensin- converting enzyme 2 (ACE2) receptor on the cell surface and then activating the S-protein via transmembrane serine protease 2 (TMPRSS2), both of which are co-expressed in intestinal epithelial cells (Dong et al., 2020). Viral particles have been detected in the small intestine of patients, mainly in MUC2-positive epithelial cells, presumably goblet cells, and in epithelial cells of crypts (Livanos et al., 2021). These studies suggest that SARS-CoV-2 virus can actively infect and replicate in the gastrointestinal tract. Disruption of intestinal epithelial cells can alter intestinal permeability, affect absorptive and secretory functions, and may explain diarrhea and other gastrointestinal manifestations (Shih and Misdraji, 2023). Meanwhile, the intestinal barrier dysfunction can trigger bacteria translocation and aggravate systemic infection and inflammation. In addition to direct viral infection, other mechanisms of gastrointestinal injury with SARS-CoV-2 may involve markedly elevated levels of inflammatory markers and cytokines (Calitri et al., 2021), as well as hypoxia due to respiratory failure, systemic coagulopathy, and right heart failure (Patel et al., 2021; Shih and Misdraji, 2023).

Studies have shown inconsistent results regarding the relationship between gastrointestinal symptoms and disease progression in COVID-19. Our study is consistent with the findings of quite a few clinical researches that patients with gastrointestinal symptoms are at higher risk for clinical deterioration than those without (Zheng et al., 2020; Zeng et al., 2022). In most of these literatures, symptoms such as anorexia, nausea, vomiting, abdominal pain, and diarrhea were grouped together as gastrointestinal symptoms. As for individual symptom, the association of diarrhea with severe disease has been variable. Approximately 10 to 20% of patients with COVID-19 develop diarrhea (Friedel and Cappell, 2023). It has been reported that late-onset diarrhea often has a poor prognosis due to COVID-19 treatments such as antibiotics, and even Clostridioides difficile infection (Friedel and Cappell, 2023). However, some studies did not report such findings, and even the presence of gastrointestinal symptoms is associated with lower circulating cytokine levels, reduced disease severity, and reduced mortality (Dong et al., 2020; Tabesh et al., 2022). Two recent meta-analysis also suggested no difference in mortality between patients with and without gastrointestinal symptoms (Shehab et al., 2021; Wang et al., 2022). These results indicate that the role of gastrointestinal involvement in the course of COVID-19 requires further investigation.

Fever is a common symptom of Omicron infection, and is often associated with adverse outcomes such as prolonged hospital stay (Wu S. et al., 2020; Guo et al., 2021) and development of ARDS (Wu C. et al., 2020). In our study, fever was associated with an approximately six-fold (OR=6.358) increase in the risk of severe disease, which is questionable given that fever occurred in only 8.3% of patients with non-severe disease. The possible reason for this is that some patients with mild symptoms only had fever before admission and did not report it during hospitalization, resulting in a huge discrepancy between the collected data and the real world.

The protective effect of COVID-19 vaccines has been proposed in previous studies (Hernandez-Teran et al., 2022; Kaur et al., 2022). In this research, we also found a trend toward a beneficial effect of full vaccination, but it was not significant which may be related to the relatively small sample size.

Since the main population of this study was patients with asymptomatic or mild symptoms, we also further analyzed VST and LOS in non-severe patients in an attempt to find more clues to adverse outcomes. We innovatively replaced a number of complex symptoms with a simple symptom score, and concluded that the symptom score was related to adverse outcomes such as prolonged VST, and prolonged LOS, which are theoretically reasonable and interpretable.

The limitations of this study are as follows. Firstly, it is a single-center retrospective study with a relatively small sample size after PSM, and studies with larger sample size are needed to confirm our conclusions. Second, viral nucleic acid RT-PCR test was not performed daily for each patient, resulting in a delay of VST compared with actual viral clearance time. Third, this study focused on patients’ symptoms and did not include laboratory or imaging findings and thus could not assess their prognostic role.

Risk factors for poor prognosis need to be identified to better understand and prevent the pandemic of COVID-19. According to our study, the overall condition of the Shanghai Omicron epidemic is relatively mild. Higher symptom score is associated with longer VST and longer hospital stay. Attention should be paid to the development of severe disease in patients with diarrhea.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

This study was reviewed and approved by the Clinical Research Ethics Committee of Jiangsu Province Hospital of Chinese Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

YG drafted the manuscript. QN and FL collected the data set. YG, YP, and H-D Z analyzed the clinical data. QC and H-Q Z submitted ethics related materials. JX and HJ designed the study. JX, HJ and JZ reviewed the final manuscript. All authors approved the final manuscript.