Epidemiological and clinical features of SARS-CoV-2 Omicron variant infection in Quanzhou, Fujian province: a retrospective study

Epidemiological and clinical data of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2) admitted to three designated hospitals in Quanzhou City, Fujian Province, China, were collected and analyzed. Overall, 2,541 patients infected with BA.2, comprising 1,060 asymptomatic, 1,287 mild, and 194 moderate infections, were enrolled. The percentage of moderate infections was higher in patients aged ≥ 60 years than in those aged < 18 years and 18–59 years. The median hospitalization duration was 17 days. Among the 2,541 patients, 43.52% had a clear history of close contact. The vaccination rate was 87.92%, and the percentage of asymptomatic infections was higher in vaccinated than in unvaccinated patients. Moreover, patients with underlying diseases, including hypertension and diabetes mellitus, had more moderate infections than those without underlying diseases. The three most common clinical manifestations were fever, dry cough, and sore throat. The albumin-to-globulin (A/G) ratio and lymphocyte count decreased in cases with mild and moderate infections, while procalcitonin, erythrocyte sedimentation rate, interleukin-6, D-dimer, and C4 levels increased. Advanced age, non-vaccination, and underlying comorbid diseases were high-risk factors for disease progression in patients. However, dynamic monitoring of blood routine parameters, A/G ratio, and inflammatory indicators facilitated the prediction of disease progression.


Source of cases
This study enrolled patients who had either asymptomatic infections or confirmed symptomatic infections of Omicron variant strain BA.2 and were admitted between March 13, 2022, and April 14, 2022, at the Chengdong Branch and Infectious Diseases Branch of Fujian Medical University Affiliated First Quanzhou Hospital, as well as the Quanzhou "Huoweishan" Cabin Hospital.Patients suspected of recovering from COVID-19 but re-tested positive for SARS-CoV-2, with previous infection of the novel coronavirus, originating from regions other than Quanzhou, and with significant missing information on medical records were excluded from this study.

Diagnostic criteria
Patients with an epidemiological history and clinical manifestation of novel coronavirus infections along with serological or pathogenic evidence were defined as having a confirmed diagnosis of COVID-19 according to the COVID-19 Diagnosis and Treatment Protocol (Trial Version 9) 7 issued by the Office of the National Health Care Commission and Office of the State Administration of Traditional Chinese Medicine.According to clinical manifestations and auxiliary examinations, confirmed cases were classified as mild, moderate, severe, and critical.Asymptomatic infections were defined as testing positive for the novel coronavirus and having no associated clinical manifestations according to the Prevention and Control Plan for Novel Coronavirus Disease (Version 8) issued by the Integrated Group of the State Council for Joint Prevention and Control of Novel Coronavirus Disease Epidemic 8 .

Data collection
Information on demographic characteristics, such as sex, age, body mass index, underlying disease, and vaccination status for COVID-19, as well as disease classification and clinical manifestations, was obtained.Auxiliary examinations, including routine tests for blood parameters, inflammatory markers, humoral immunity, T-lymphocyte subsets (absolute counts), coagulation, complete biochemical parameters, and COVID-19 antibodies; quantitative reverse-transcription polymerase chain reaction (RT-qPCR) cycle threshold (CT) for nucleic acid testing; pulmonary imaging (except in pregnant women); and post-treatment testing, were performed within 48 h of admission.Moreover, each case was evaluated as to whether Western or traditional Chinese medical treatments were to apply.The efficacy was evaluated by recording the time interval from testing positive to testing negative for SARS-CoV-2.Strict regulations of database management were implemented to ensure data security and confidentiality.

Statistical methods
All statistical analyses were performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA).Measurement data were analyzed using the Kruskal-Wallis rank-sum or Mann-Whitney U tests and expressed as medians (25th and 75th percentiles).Count data were subjected to the χ2 or Fisher's exact test and expressed as percentages.Differences with a P-value of < 0.05 were considered statistically significant.

Epidemiological, demographic, and clinical features
A total of 2,541 patients infected with SARS-CoV-2 Omicron sublineage (BA.2) were enrolled in this study, of whom 1,060 (41.72%) were asymptomatic, and 1,481 (58.28%) had a confirmed diagnosis of COVID-19.Of the confirmed cases, 1,287 (86.90%) were mild and 194 (13.10%) were moderate, but there were no severe or critical cases.Of the 2,541 patients, 1,106 (43.52%), 901 (35.47%), and 34 (21.01%) had a confirmed, uncertain, and no history of contact, respectively.Regarding the number of infected patients (whether asymptomatic or confirmed cases), most patients were from Fengze District (46.80% and 55.15%), followed by Jinjiang City, Licheng District, Shishi City, Luojiang District, Nan'an City, Hui'an County, Dehua County, and Quangang District.Meanwhile, no confirmed cases were reported in Yongchun County, and no Omicron variant infections were reported in Anxi County (Fig. 1).The percentages of patients who received the one, two, and three doses of the COVID-19 vaccine were 5.16%, 41.95%, and 40.82%, respectively, while that of unvaccinated patients was 10.19%.The percentage of asymptomatic infections was higher while the percentage of mild infections was lower in vaccinated than in unvaccinated patients (42.75% vs. 36.29%,χ 2 = 3.97, P = 0.046; and 49.69% vs. 56.76%,χ 2 = 4.64, P = 0.031; respectively).However, there was no significant difference in the percentage of moderate infections (7.56% vs. 6.95%,P = 0.72) between the vaccinated and unvaccinated groups, with no association of the between-group difference or similarity with the number of doses of the COVID-19 vaccine.

Results of auxiliary examinations within 48 h of admission
Abnormal alanine transaminase (ALT) levels and hypo-albuminemia were observed in 190 (7.48%) and 312 (12.28%) patients, respectively (Table 2).The lymphocyte count and albumin-to-globulin ratio (A/G) were higher in asymptomatic cases than in mild and moderate cases (all P < 0.01), while asymptomatic cases had lower levels of C-reactive protein (CRP), complement C4, interleukin-6 (IL-6), prothrombin, globulin (GLB), and D-dimer than mild and moderate cases (all P < 0.05).White blood cell, neutrophil, and platelet counts; total bilirubin (TBIL), ALT, and gamma-glutamyl transferase (GGT) levels; as well as CD3 + and CD4 + T-cell counts were higher in asymptomatic cases than in mild cases (all P < 0.01).Meanwhile, asymptomatic cases had a lower international normalized ratio than mild cases (P < 0.001), as well as a lower erythrocyte sedimentation rate (ESR) and immunoglobulin levels than moderate cases (all P < 0.01).Blood urea nitrogen levels were higher in asymptomatic cases, and albumin (ALB) levels were higher in mild cases than in moderate cases (both P < 0.05).

Risk factors for delayed discharge or release from quarantine
To explore the risk factors for delayed discharge or release from quarantine, patients with incomplete laboratory results were excluded from the analysis.Subsequently, using the median length of hospital stay of 17 days as the threshold, patients were divided into the control (< 17 days, n = 1210) and observation (≥ 17 days, n = 1331) groups.Crude logistic regression analysis showed that sex, disease classification, as well as lymphocyte and platelet counts, were related to delays in discharge or release from quarantine.Multivariable logistic regression analysis showed that only the disease classification and lymphocyte count were risk factors for delayed discharge or release from quarantine (Table 3).

Discussion
This retrospective clinical study involved patients infected with the community-transmitted SARS-CoV-2 Omicron BA.2 in China.Our results show that patients with SARS-CoV-2 Omicron BA.2 infection in Quanzhou were associated with lower median age, mild clinical presentation, shorter hospital stays, no severe cases and deaths, higher coverage of COVID-19 vaccine, and better prognosis compared with those infected with the original strain (Fig. 2).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 9 .
The predominance of asymptomatic infections in the vaccinated patients in this study and that of mild infections in the unvaccinated patients suggest that COVID-19 vaccination is protective against the Omicron variant, and the protective effect is independent of the number of vaccination doses.
Existing studies have suggested that women are less susceptible to SARS-CoV-2 due to the protective effects of the X chromosome and sex hormones 10 , with a lower risk of death in women infected with SARS-CoV-2 than in men (hazard ratio 1.59, 95% confidence interval: 1.53-1.65) 11.In contrast, this study shows that the percentage of infected men was lower than that of infected women (47.93% vs. 52.07%).Moreover, the percentage of men with moderate infections was significantly lower than that of men with asymptomatic infections, suggesting that women are more susceptible to the Omicron variant 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 [12][13][14] .Although patients aged ≥ 60 accounted for only 8.62% of the enrolled population, a higher percentage of them were with moderate infections than those aged < 18 and 18-59 years, suggesting that older age is still an important factor influencing disease progression.Another independent risk factor for disease progression is underlying comorbid disease 15 rather than various mutations in the Omicron sublineage BA.2.2 16 .The role of underlying diseases in the progression of Omicron infections was further highlighted by the fact that 10.82% of the patients in our study had comorbidities, and 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 Omicron BA.2 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 and ageusia, conjunctivitis, nausea, and vomiting were relatively rare, consistent with the results reported in a South Korea-based study 17 .The relatively high percentage of asymptomatic infections poses a great challenge to effective prevention and control of the pandemic.Furthermore, nucleic acid testing and COVID-19 antigen detection remain important tools to help in dynamic monitoring of the pandemic and prompt identification of infected persons 18 .Although asymptomatic and mild infections do not lead to changes in pulmonary imaging, the imaging parameter plays an irreplaceable role in clinical diagnosis and staging.Similar to the original SARS-CoV-2 strain, infections with the Omicron variant can also damage the lungs.In our study, damage 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 pulmonary lesions in patients infected with the Omicron variant were significantly smaller or nodular, consistent with that reported in an Italian study 19 .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 20,21 .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 counts are significantly and positively associated with mortality 22 .Although there were no fatalities in this study, it is apparent that lymphocyte count was significantly reduced in moderate and mild infections compared with that in asymptomatic infections, which is consistent with the results of a previous Chinese study 23 .Inflammatory indicators of infection, such as procalcitonin (PCT), ESR, IL-6, and D-dimer levels, are effective predictors of mortality in inpatients in intensive care units 24 .In this study, the 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, the CRP level, ESR, and leukocyte count were not simultaneously elevated to a high level.This observation ruled out the possibility of bacterial infections and suggested that over-activation of the IL-6 signaling pathway by the Omicron variants may be involved.However, the specific mechanism needs further investigation.These results suggest that dynamic monitoring of routine blood parameters, especially lymphocyte count and inflammatory indicators of infection, is useful in predicting the severity of the disease.
A previous study showed that the incidence of liver dysfunction in patients with COVID-19 was approximately 14-53% 25 , which was significantly higher than that observed in this study (7.48%).Our results can potentially be attributed to milder infections and the Omicron variant.Although levels of ALB, GLB, ALT, GGT, and TBIL in most infected patients were within normal ranges, approximately 12.28% of these patients still developed hypo-albuminemia, a condition that can be used as a marker to assess the severity of injury to the endothelial cells of the pulmonary capillary in infected patients 26 .Low ALB levels and high GLB levels in moderate infections led www.nature.com/scientificreports/ to a further decrease in the A/G ratio, and thus monitoring the A/G ratio helps determine the prognosis of the disease.Serum ferritin and lactate dehydrogenase are considered predictors of disease severity and progression in SARS-CoV-2-infected patients 27 ; however, neither was associated with disease severity in Omicron variantinfected 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 28 .
Several studies have demonstrated the presence of complement system activation in patients with COVID-19, as evidenced by a decrease in both complement C3 and complement C4 levels, as well as a significant correlation between the decrease in disease severity and high mortality 29,30 .Complement C4 level dropped in only 2.94% of infected patients in this study but was progressively elevated in asymptomatic, mild, and moderate infections, suggesting that the increase in complement C4 level is associated with disease severity in Omicron variant-infected patients.Further, high complement C3 level is an independent risk factor for delayed hospital discharge in patients infected with the original SARS-CoV-2 strain 13 .
This study has some limitations.First, all investigated infections originated only from the Quanzhou area, and there were no severe cases; hence, the epidemiological and clinical features did not comprehensively cover all SARS-CoV-2 Omicron infections.Second, the incubation period, CT of RT-qPCR for nucleic acid testing, and duration of symptoms of infected patients were not investigated.Third, the effect of the traditional Chinese medicine decoction on disease outcomes was not clarified.Although traditional Chinese medicine can play a role in adjuvant therapy, it is not the main therapy.Traditional Chinese medicine has certain advantages in relieving symptoms, improving immunity, and promoting rehabilitation, which has been involved in the treatment of patients with COVID-19 enrolled in this research institute.In this study, all patients with COVID-19 were treated with traditional Chinese medicine decoction as Yiqi Jiedu prescription, and clarifying its effect was impossible without comparison to other treatments or controls.
Despite these limitations, this was a rare real-world study of a large number of COVID-19 community infections in coastal areas of China.The number of infected patients included was large, and all infected patients were hospitalized.The observation and judgment of the condition of infected people were supported by medical staff with professional knowledge.This is a comprehensive and objective study with a detailed description of the demography, clinical manifestations, imaging features of the lung, and clinical outcomes of infected patients, which would have a certain clinical reference value.
In conclusion, this study revealed 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 and death-related cases.This study reveals, to a certain extent, the basic characteristics and prognostic outcomes of Omicron BA.2 infections.Our findings would provide a reference for the prognostic prediction and medical resource allocation regarding Omicron BA.2 infections.

Table 3 .
Crude and adjusted logistic regression analyses of the risk factors for delayed discharge from the hospital.CI, confidence interval; OR, odds ratio; PLT, platelet count.