This retrospective clinical study involved many patients infected by the community-transmitted SARS-CoV-2 Omicron variant in China. The results showed that patients with SARS-CoV-2 Omicron variant COVID-19 in Quanzhou had a low median age, mild clinical manifestations, short hospitalization duration, and good prognosis without any severe infections or deaths associated with a high vaccination rate against the virus (87.92%). Despite the relatively low virulence of the Omicron variant, unvaccinated older adults, especially those with underlying comorbid diseases, were at high risk of suffering from both severe infection and death 7. The predominance of asymptomatic infections in the vaccinated patients in this study and that of mild infections in the unvaccinated patients suggested that COVID-19 vaccination is still protective against the Omicron variant and that this protective effect is independent of the number of vaccination doses.
Existing studies suggest that women have a lower susceptibility to SARS-CoV-2 due to the protective effects of the X chromosome and sex hormones 8 and that women with SARS-CoV-2 infections have a lower risk of death than men (hazard ratio 1.59, 95% confidence interval 1.53-1.65) 9. In contrast, this study showed that the percentage of infected male individuals was lower than that of infected female individuals (47.93% vs. 52.07%) and that the percentage of male individuals among patients with moderate infections was significantly lower than that of male individuals among patients with asymptomatic infections, suggesting that female individuals are more susceptible to the Omicron variant sublineage BA.2 and more likely to have moderate infections. Unlike those infected with the original SARS-CoV-2 strain, the median age of patients infected with the Omicron variant was relatively low, with a downward shift in the age of infection 10-12. Although patients aged ≥60 accounted for only 8.62% of the enrolled population, they had a higher percentage of moderate infections than those aged <18 and 18-59, suggesting that older age is still an important factor influencing disease progression. Another independent risk factor for disease progression is underlying comorbid disease 13 rather than various mutations in the Omicron sublineage BA.2.2 14. The role of underlying disease in the progression of Omicron infections was further highlighted by the fact that 10.82% of the patients in this study had comorbidities and that the percentage of moderate infections was higher in this sub-population than in the rest of the patients without pre-existing conditions.
In this study, 41.72% of the patients infected with the Omicron variant were asymptomatic, and the clinical manifestations of confirmed cases were relatively mild. The most common symptoms of confirmed cases were fever, dry cough, sore throat, fatigue, and muscle aches; meanwhile, anosmia of taste and smell, conjunctivitis, and nausea and vomiting were relatively rare, consistent with that reported in a South Korea-based study 15. The relatively high percentage of asymptomatic infections poses a great challenge to the prevention and control of the pandemic, with nucleic acid testing and COVID-19 antigen detection as the important tools for the timely identification of infected patients and dynamic monitoring of the disease 16. Although asymptomatic and mild infections do not lead to pulmonary imaging changes, pulmonary imaging plays an irreplaceable role in clinical diagnosis and staging. Similar to the original SARS-CoV-2 strain, infections of the Omicron variant also damage the lungs, which manifested as patchy and ground-glass opacities in computed tomography images, with most lesions distributed in the peripheral zone and the subpleural areas. The difference was that the pulmonary lesions in patients infected with the Omicron variant were significantly smaller or even nodular, consistent with that reported in a study in Italy 17. The main reason for this difference is that the Omicron variant has a reduced binding capacity to the TMPRSS2 protein, significantly reducing the amount of virus entering the lung cells 18, 19.
Moreover, laboratory tests play an integral role in monitoring the severity of the disease and its treatment. Current studies have shown that decreased lymphocyte and increased neutrophil count are significantly and positively associated with mortality 20. Although there were no fatalities in this study, it is apparent that lymphocyte counts were significantly reduced in moderate and mild infections compared with asymptomatic infections, which was consistent with that reported in a study in China 21. Inflammatory indicators of infection, such as PCT, ESR, IL-6, and D-dimer levels, are effective predictors of mortality in intensive care unit inpatients 22. PCT, ESR, IL-6, and D-dimer levels were progressively elevated during asymptomatic, mild, and moderate infections. In particular, the IL-6 level was significantly elevated, with 7.48% of infected patients having an IL-6 level of >1,000 mg/L and 2.32% of infected patients surpassing the upper limit (>5,000 mg/L). Meanwhile, CRP, ESR, and leukocyte count were not simultaneously elevated to a high level. This observation ruled out the possibility of bacterial infections and suggested that the over-activation of the IL-6 signaling pathway by the Omicron variants may be involved, while the specific mechanism should be further investigated. These results suggest that dynamic monitoring of blood routine parameters, especially lymphocyte count and inflammatory indicators of infection, is useful in predicting the severity of the disease.
The incidence of liver dysfunction in COVID-19 patients was reported at approximately 14-53% 23, which was significantly higher than in this study (7.48%) and can be attributed to the milder infections and Omicron variant in this study. Although most infected patients had ALB, GLB, ALT, GGT, and TBIL levels within normal ranges, 12.28% still developed hypo-albuminemia, a condition that can be used as a marker to assess the severity of pulmonary capillary endothelial cell injury in infected patients 24. Low ALB levels and high GLB levels in moderate infections led to a further decrease in the A/G ratio, and monitoring the A/G ratio helps determine the disease's prognosis. Serum ferritin and lactate dehydrogenase are considered predictors of disease severity and disease progression in SARS-CoV-2 infected patients 25, while neither was associated with disease severity in Omicron variant-infected patients in this study. Moreover, this study did not observe acute kidney injury induced by the interaction of SARS-CoV-2 nucleoproteins with Smad3 signaling molecules 26.
Several studies have demonstrated the presence of complement system activation in COVID-19 patients, as evidenced by a decrease in both complement C3 and complement C4 levels, as well as a significant correlation of the decrease with disease severity and high mortality 27, 28. Complement C4 level dropped in only 2.94% of infected patients in this study but was progressively elevated during asymptomatic, mild, and moderate infections, suggesting that the increase in complement C4 level was associated with disease severity in Omicron variant-infected patients and that high complement C3 level is an independent risk factor for delayed hospital discharge in patients infected with the original SARS-CoV-2 strain 11.
This study had some limitations. First, all the investigated infections originated only from the Quanzhou area, and there were no severe cases, making it impossible to describe all the epidemiological and clinical features of SARS-CoV-2 Omicron infections. Second, the incubation period, RT-qPCR CT for nucleic acid testing, and duration of symptoms of infected patients were not investigated. Third, all infected patients were treated with a traditional Chinese medicine decoction, and it was impossible to clarify the effect of the decoction on disease outcome.
In conclusion, this study showed that patients infected with the SARS-CoV-2 Omicron variant in Quanzhou had a high rate of novel coronavirus vaccination, mild clinical manifestations, short hospitalization duration, and good prognosis, with no severe case and death case. This study revealed to a certain extent, the basic characteristics and prognostic outcomes of Omicron variant infections, and the findings provide a reference for the prognostic prediction and medical resource allocation of Omicron variant infections.