Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2 Weijie Zhong Zhong, Xiaosheng Yang, Xiufeng Jiang, Zhixin Duan, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1980808/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background To explore the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron. Methods Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to the shedding time of omicron [≥ 10 days, "late clearance group" and < 10 days, "early clearance group"]. Results 180 patients were enrolled in the study (88 early, 92 late), with a median time of viral shedding was 10 days and a mean age of 77.02 years. When comparing patients between either group, prolonged SARS-CoV-2 omicron shedding was associated with old age ( P = 0.007), unvaccinated ( P = 0.001), delayed admission to hospital after illness onset ( P = 0.001), D-dimer ( P = 0.003) and methylprednisolone treatment ( P = 0.048). In the multivariable analysis, vaccinated [OR], 0.319 [95% CI, 0.130–0.786], P = 0.013), paxlovid (OR, 0.259 [95% CI, 0.104–0.643], P = 0.004), and time from onset to admission (OR, 1.802 [95% CI, 1.391–2.355], P = 0.000) were significantly associated with viral clearance. Conclusions The older age, methylprednisolone therapy, and D-dimer were associated with prolonged duration of omicron viral shedding. The time from onset to hospitalization, unused paxlovid and unvaccinated were independent risk factors in patients infected with SARS-CoV-2 omicron. viral shedding time SARS-CoV-2 Omicron factors Figures Figure 1 Figure 2 Introduction Coronavirus Disease 2019 (COVID-19) was identified in January 2020 and has been swept by human‑to‑human transmission [ 1 , 2 ] . Five variants of concern (VOC) have been identified so far, namely Alpha, Beta, Gamma, Delta, and Omicron variants designated by the World Health Organization (WHO) [ 3 , 4 ] . The rapid spread of the omicron variant was first identified on November 24, 2021, and became the predominant variant, posing a severe threat worldwide [ 5 , 6 ] . Compared to DNA viruses, RNA viruses have a higher mutation [ 7 ] . During the COVID-19 pandemic [ 8 , 9 ] , researchers indicated that the variant of omicron is the most mutated strain in the midst of SARS-CoV-2 variants, which may help the virus evade infection-blocking antibodies [ 7 ] . These mutations will affect the characteristics of the SARS-CoV-2 omicron, including infectivity, immune escape, viral shedding time, and outcome. Data showed that the infectivity of SARS-CoV-2 omicron variants 10-fold higher than that of the original virus, but they were less likely to be admitted and require ICU level care [ 10 ] . In addition, reinfection was observed approximately 10 times more frequently than in the Delta variant [ 11 , 12 ] . Therefore, omicron will significantly impact the therapeutic effect of COVID-19 drugs, immunity secondary to vaccination or prior infection, infectivity, and outcome [ 13 ] . In 2022, a wave of COVID-19 rapidly appeared in shanghai, China. After comparing the genomes of viruses, it was found that the genomes of the infected viruses in Shanghai belong to the Omicron BA.2.2 [14, 15,] . Zhang et al. found that the total cases in Shanghai were higher while the severity rate and mortality was lower, similar to other countries [ 5 ] . Moreover, studies of people infected with omicron variant suggested that older age might potentially predict mortality and severity [ 16 , 17 ] . Understanding the kinetics of infectious viral shedding to possible transmission risk is crucial to guiding infection prevention and control strategies [ 18 ] . Therefore, it is essential to understand the shedding time of the variant of omicron since it is a crucial factor in the guidance of decisions about isolation precaution and antiviral treatment [ 19 , 20 ] . Through a retrospective cohort study, including 59 hospitalized patients with COVID-19, the elderly was independently associated with long-term virus shedding [ 21 ] . Another study demonstrated that sex, corticosteroid, and Delayed admission is an independent risk factor for prolonged virus shedding time in COVID-19 patients [ 22 ] . However, whether these findings are also applicable to the omicron variants is still unclear. Up to June 24, 2022, we have used the search terms ("Omicron") and ("shedding time") and ("prolonged") to search PubMed and found no relevant articles. In short, the relationship between omicron viral shedding time and risk factors has not been fully clarified. Hence, this study aimed to evaluate the characteristics of viral shedding time with older patients infected with omicron and identify risk factors influencing the duration of viral shedding. Methods Patients enrollment 361 participants with confirmed SARS-CoV-2 Omicron BA.2.2 admitted to the Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled for analysis. (Fig. 1 ). Participants were diagnosed with SARS-CoV-2 according to the guidelines of China (version 9). The earliest patient was admitted on April 23, 2020. According to the characteristics of SARS-CoV-2 omicron, older patients are a risk factor for exacerbation of the disease. Hence, this study was aim to explore the occurrence of the viral shedding in older patients infected with omicron variants. Inclusion criteria: 1) Ct value<35 for both ORF1ab and N gene; 2) age ≥ 60. According to the criteria, 180 patients were enrolled. Among all patients, the viral shedding time of 88 patients was within 10 days, and that of 92 patients was over 10 days. This trial received approval from the Ethics Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No. SH9H-2022-T112-2) and registered at the Chinese Clinical Trial Registry (ChiCTR2200060700). Trial procedures This retrospective cohort study was designed to assess the time of virus shedding in elderly participants infected with SARS-CoV-2 omicron (Fig. 1 ). Patients whose viral shedding time was less than 10 days were included in the early viral clearance group, and patients whose viral shedding time was more than or equal to 10 days were included in the late viral clearance group. Clinical characteristics and treatment of patients were collected using electronic medical records. The clinical characteristics were as follows: 1) age, mean; 2) cycle threshold value (CT. N and ORF); 3) time from onset to enrollment in patients; 4) gender; 5) condition at admission; 6) vaccine status; 7) comorbidity; 8) first symptoms; 9) laboratory indicators 10) time from the first admission to the negative testing; 11) viral shedding time. The treatment of patients was as follows: 1) medication; 2) auxiliary breathing; 3) whether to enter ICU. Definition Nucleic acid negative test is recognized as viral shedding (two consecutive, Ct value༞35 for the ORF and N gene) and was quantified by RT-PCR [ 5 ] . The time to viral shedding was from the first positive nucleic acid test to successive negative detection. Time from onset to patient enrollment was considered the time from the first positive nucleic acid test to the date of first hospitalization [ 23 , 24 ] . Conditions at admission were included: 1) asymptomatic cases; 2) mild cases; 3) moderate cases; 4) severe cases, according to Chinese guidelines (version 9). Charlson comorbidity index is a widely used complication scoring system involving 17 diseases [ 25 ] . Medication is the therapeutic drugs used during hospitalization, including paxlovid, anticoagulation, methylprednisolone, and Chinese medicine. Assisted breathing includes nasal tube oxygen inhalation, mask oxygen inhalation, ventilator oxygen inhalation, and ECMO. Statistical analysis Categorical variables were described as numbers (%), and continuous variables were described as median (IQR) or mean (Standard Deviation, SD). Continuous variables were compared with the Mann-Whitney U test or Student's t test, and categorical variables were compared by the χ² test or Fisher's exact tests. Logistic regression was employed to analysis risk factors, adjusted odds ratio (OR and 95%CI were calculated. P-values < 0.05 were considered statistically significant). The different rate of negative nucleic acid test between-group was compared by the Kaplan-Meier method with a log-rank test. Results Characteristics of participants in this trial The study included 180 older participants infected with the variants of omicron. Among 180 participants, the median time of viral shedding was 10 days, and 104 (57.78%) were female with the mean age was 77.02. Among all patients, the median time from onset to enrollment was 1 day (1–3 days), and the viral shedding time was 10 days (8–12 days). Most patients were mild cases, and only 1 case (0.56%) was diagnosed as severe cases. Among the 180 patients, 56 (31.11%) were vaccinated, and 124 (68.89%) were unvaccinated. During hospitalization, 174 (96.67%) patients were treated with traditional Chinese medicine, followed by 134 (74.44%) patients treated with paxlovid. In addition, 28 (15.56%) patients needed nasal catheter assisted oxygen inhalation during hospitalization. Risk factors for the viral shedding The purpose of this study was to observe the virus shedding time of elderly patients infected with SARS-CoV-2 omicron. Then, Participants were further divided into two groups; one was the viral shedding time＜10 days (n = 88), and another was the viral shedding time ≥ 10 days (n = 92). Clinical characteristics, epidemiological, treatment, laboratory indicators, and outcomes were compared between either (Table 1 ). No significant differences were found in the Ct value, or sex, between either group. Variables with statistical significance ( P < 0.05) between two groups, including age (75.05 vs. 78.91, P = 0.007), vaccinated [38 (43.18%) vs. 18 (19.57%), P = 0.001)], D-dimer (0.48 vs. 0.97, P = 0.030), time from onset to enrollment (1 vs. 3, P = 0.001) and time from the first day admission to the negative testing (6.18 vs. 8.7, P = 0.001). Compared with the late viral clearance group, the early viral clearance group had more patients using paxlovid [74 (84.09%) vs. 60 (65.22), P = 0.004). However, patients who used methylprednisolone were higher in the late viral clearance group than in the early [6 (6.81%) vs. 15 (16.30%), P = 0.048)]. In addition, the ratio of severe cases at first hospitalization in the late group was higher than that in the early group (0% vs. 1.09%), but no significant differences were found in the condition at admission. Moreover, we found that the mean of Charlson was higher in the late viral clearance group (0.76 vs. 1.09, P = 0.051). Table 1 Comparison of clinical characteristics and treatment responses between groups with different viral shedding time Characteristics Total N = 180 Viral shedding time P-value P-value* ＜10 days N = 88 ≥ 10days N = 92 Age, mean (SD), year 77.02 (9.74) 75.05 (9.73) 78.91 (9.42) 0.007 0.008 CT.N, mean (SD) a 28.80 (2.87) 28.50 (2.91) 29.06 (2.82) 0.196 0.254 CT.ORF, mean (SD) 28.18 (3.36) 27.72 (3.43) 28.71 (3.24) 0.047 0.076 Time from onset to enrollment in patients, median (IQR), day b 1 (1–3) 1 (1–2) 3 (1–5) < 0.001 < 0.001 Time from the first day treatment to the negative testing, mean (SD), day 7.47 (2.65) 6.18 (1.35) 8.7 (2.99) < 0.001 < 0.001 Sex 0.515 - Male, n (%) 76 (42.22%) 35 (39.77%) 41 (44.57%) Female, n (%) 104 (57.78%) 53 (60.23%) 51 (55.43%) Condition at admission c 0.150 - Asymptomatic cases, n (%) 12 (6.67%) 9 (10.23%) 3 (3.26%) mild cases, n (%) 142 (78.89%) 67 (76.13%) 75 (81.52%) moderate cases, n (%) 25 (13.89%) 12 (13.63%) 13 (14.13%) severe cases, n (%) 1 (0.56%) 0 (0.00%) 1 (1.09%) Vaccine < 0.001 - Unvaccinated, n (%) 124 (68.89%) 50 (56.82%) 74 (80.43%) vaccinated, n (%) 56 (31.11%) 38 (43.18%) 18 (19.57%) Comorbidity Hypertension, n (%) 110 (61.11%) 53 (60.23%) 57 (61.96%) 0.812 - Diabetes, n (%) 41 (22.78%) 15 (17.05%) 26 (28.26%) 0.073 - Coronary artery disease, n (%) 32 (17.78%) 19 (21.59%) 13 (14.13%) 0.205 - Charlson, median(IQR) d 1 (0–1) 1(0–1) 1 (0–2) 0.051 0.101 First symptoms Fever n (%) 84 (46.67%) 43 (48.86%) 41 (45.05%) 0.610 - Fatigue, n (%) 45 (25%) 24 (27.27%) 21 (22.83%) 0.491 - Cough, n (%) 141 (78.33%) 66 (75%) 75 (81.52%) 0.288 - Expectoration, n (%) 109 (60.56%) 52 (59.09%) 57 (61.96%) 0.694 - runny nose, n (%) 56 (31.11%) 24 (27.27%) 32 (34.78%) 0.277 - Sore throat, n (%) 64 (35.56%) 39 (44.32%) 25 (27.17%) 0.016 - Laboratory indicators WBC, mean (SD), /L) 4.95 (1.48) 4.71 (1.40) 5.18 (1.52) 0.850 0.064 L, mean (SD), /L 1.32 (0.57) 1.25 (0.45) 1.39 (0.65) 0.124 0.163 ALT, median (IQR), U/L 17 (12.25-25) 21.78 (13-27.5) 22.15 (12–25) 0.336 0.230 AST, median (IQR), U/L 26.50 (22–33) 27 (21.5–34) 30.40 (23–33) 0.823 0.547 Prothrombin time, mean (SD), s 10.98 (0.82) 10.98 (0.8) 10.98 (0.84) 0.711 0.841 APTT, mean (SD), s 29.43 (3.20) 29.09 (2.83) 29.76 (3.50) 0.230 0.117 Fibrinogen, mean (SD), g/dL 3.20 (0.78) 3.09 (0.63) 3.30 (0.89) 0.016 0.174 Fibrinogen＜2, n (%) 29 (16.11%) 9 (10.23%) 20 (21.74%) 0.07 - D-dimer, mean (SD), mg/L 0.43 (0.26–0.79) 0.48 (0.21–0.64) 0.97 (0.28–0.99) ＜0.001 0.003 D-dimer＞0.5, n (%) 72 (40%) 27 (30.68%) 45 (48.91%) 0.030 - CRP, mean (SD), mg/L 5.44 (2.28–13.8) 8.49 (2.07–10.94) 13.9 (2.36–15.17) 0.05 0.229 CRP＞10, n (%) 56 (31.11%) 24 (27.27%) 32 (34.78%) 0.345 - Treatment Nasal duct, n (%) 28 (15.56%) 12 (13.64%) 16 (17.39%) 0.487 - Paxlovid, n (%) 134 (74.44%) 74 (84.09%) 60 (65.22%) 0.004 - Anticoagulation, n (%) 32 (17.78%) 11 (12.50%) 21 (22.83%) 0.070 - Methylprednisolone, n (%) 21 (11.67%) 6 (6.81%) 15 (16.30%) 0.048 - Chinese medicine, n (%) 174 (96.67%) 86 (97.73%) 88 (95.65%) 0.438 - * Indicated U test. a Real-time PCR Ct value. b Time from onset to enrollment in patients, including the time of initial symptoms or the first positive nucleic acid. c According to WHO criteria. d Charlson comorbidity index. Factors associated with the shedding time Variables with statistical significance ( P < 0.05) between two groups, including vaccination status, age, time from onset to enrollment, use of paxlovid, use of methylprednisolone, D-dimer, and Charlson, were tested. The results showed that the vaccinated (OR, 0.319 [95% CI, 0.130–0.786], P = 0.013), used paxlovid (OR, 0.259 [95% CI, 0.104–0.643], P = 0.004), time from onset to enrollment (OR, 1.802 [95% CI, 1.391–2.355], P = 0.000), and D-dimer (OR, 2.005 [95% CI, 0.975–4.121], P = 0.059) were independent factors associated with the time of viral shedding (Table 2 ). Kaplan Meier curve analysis indicated the cumulative viral negative proportion was higher in patients admitted to hospital within 3 days after the first nucleic acid positive ( P = 0.0001; Fig. 2 A). Moreover, patients in the vaccinated group had a higher probability of faster virus shedding than the unvaccinated group ( P = 0.0001, Fig. 2 B). SARS-CoV-2 omicron clearance was delayed in participants who did not use paxlovid during hospitalization compared with those who used paxlovid ( P = 0.006, Fig. 2 C). Table 2 Multivariable analyses of factors associated with duration of viral shedding time Variable Multivariable analysis Odds ratio (OR) 95% CI P-value Age 1.024 0.983–1.067 0.246 Vaccinated 0.319 0.130–0.786 0.013 Time from onset to enrollment in patients, days 1.802 1.391–2.355 0.000 Paxlovid 0.259 0.104–0.643 0.004 Methylprednisolone 2.390 0.713–8.016 0.158 D-dimer 2.005 0.975–4.121 0.059 Charlson 1.288 0.928–1.787 0.130 Clinical characteristics related to Paxlovid and vaccination status There were 56 patients vaccinated, and 124 were unvaccinated (Table 3 ). We did not found significant difference after compared to the two groups. However, the time from the first-day admission to the negative testing was prolonged in the unvaccinated group (7.85 vs. 6.62, P = 0.004). During our study, 134 patients were treated with paxlovid, and 46 patients were not used. Participant characteristics were similar between the two groups (Table 3 ). Not using paxlovid group and using paxlovid group was significantly associated with the time from the first-day admission to the negative testing (8.26 vs. 7.19, P = 0.018). Table 3 Comparison of clinical characteristics between groups of vaccine status or paxlovid status. Parameters Vaccine status Paxlovid Unvaccinated N = 124 Vaccinated N = 56 P-value Unused N = 46 Used N = 134 P-value Age, mean (SD), year 78.79 (9.73) 73.11 (8.61) < 0.001 77.20 (9.99) 76.96 (9.69) 0.889 Sex 0.156 0.216 Male, n (%) 48 (38.71%) 28 (50%) 23 (50%) 53 (39.55%) Female, n (%) 76 (61.29%) 28 (50%) 23 (50%) 81 (60.45%) Condition at admission 0.696 0.675 Asymptomatic cases, n (%) 9 (7.26%) 4 (7.14%) 2 (4.35%) 11 (8.21%) mild cases, n (%) 102 (82.26%) 49 (87.50%) 39 (84.78%) 112 (83.58%) moderate cases, n (%) 12 (9.68%) 3 (5.36%) 5 (10.87%) 10 (7.46%) severe cases, n (%) 1 (0.81%) 0 0 1 (0.75%) CT.N, mean (SD) 28.79 (2.94) 28.79 (2.74) 0.996 29.20 (2.73) 28.65 (2.91) 0.259 CT.ORF, mean (SD) 28.32 (3.39) 28.03 (3.32) 0.592 28.79 (3.17) 28.04 (3.41) 0.191 Time from onset to enrollment in patients, median (IQR), day 1 (1-3.25) 1 (1–2) 0.340 2 (1–4) 1 (1–3) 0.169 Charlson, median(IQR) d 1 (0–1) 0 (0-1.25) 0.310 1 (0–2) 1(0–1) 0. 843 WBC, mean (SD), /L) 4.93 (1.48) 5 (1.48) 0.796 5.22 (1.57) 4.86 (1.43) 0.151 L, mean (SD), /L 1.30 (0.90–1.70) 1.25 (1-1.60) 0.960 1.30 (1-1.70) 1.20 (0.90–1.60) 0.478 D-dimer, mean (SD), mg/L 0.45 (0.28–0.79) 0.37 (0.21–0.64) 0.092 0.47 (0.27–0.83) 0.42 (0.25–0.75) 0.212 WB＜4.0, n (%) 34 (27.42%) 14 (25%) 0.734 9 (19.57%) 39 (29.10%) 0.207 L＞1.0, n (%) 41 (33.06%) 17 (30.36%) 0.719 14 (30.43%) 44 (32.84%) 0.764 D-dimer＞0.5, n (%) 55 (44.35%) 17 (30.91%) 0.091 21 (45.65%) 51 (38.35%) 0.384 CRP＞10, n (%) 34 (27.42%) 22 (40%) 0.094 15 (32.61%) 41 (30.83%) 0.822 Viral shedding time, mean (SD), day 10.76 (3.34) 8.95 (2.53) < 0.001 11.48 (3.08) 9.75 (3.15) 0.002 Time from the first day treatment to the negative testing, mean (SD), day 7.85 (2.85) 6.62 (1.92) 0.004 8.26 (2.78) 7.19 (2.56) 0.018 Discussion There are few investigation of the omicron variant shedding time. To the best of our knowledge, this retrospective trial aims to evaluate the risk factors associated with the time of viral shedding in the elder Chinese participants infected with omicron (age ≥ 60). We found that age, methylprednisolone therapy, longer time from onset to admission and D-dimer were associated with prolonged viral shedding. Moreover, results indicated that time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron (Table 2 ). Many mutation changes were found across the omicron, significantly impacting the immunity secondary to vaccination or prior infection and the efficacy of therapeutic drugs [ 13 ] . Unvaccinated patients had a longer viral shedding time than vaccinated patients with SARS-CoV-2 omicron in our study [38 (43.18%) vs. 18 (19.57%)]. This observation may demonstrate that the vaccine has a role in accelerating the virus shedding of elderly patients infected with omicron. The findings are consistent with a prospective, observational study, which indicated that the vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients infected with omicron [ 26 ] . Like this research, Fan et al. proposed that the vaccine can provide effective protection against the variants of omicron, although there will be a percentage of breakthrough infections [ 27 ] . However, our results only show that the vaccine can shorten the viral shedding time in this population. It can not be explained whether it can improve the severe disease rate and reduce the infection rate. In previous research, a study to observe the factors associated with viral shedding among a cohort of COVID-19 patients indicated that male participants had longer viral shedding and more severe symptoms than females infected with COVID-19 [ 28 ] . Unlike their results, we found no difference between gender and viral shedding time in patients with omicron. This result is consistent with a recent study [ 29 ] . Among the 180 patients, the mean age was 77.02 years. We found that older age could prolonged duration of viral shedding. It might be related to age-related comorbidities that may result in prolonged viral shedding [ 30 ] . In the analysis of complications, we found differences in charlson comorbidity index between either group, but there was no significant difference in hypertension, diabetes, or chronic lung disease between them. We considered that the reason for this phenomenon is that the patients we included are older, so the proportion of patients with complications is higher than the average level. Therefore, the impact of a single comorbidity is relatively weak. We also found that a long time from onset to admission could also prolonged duration of viral shedding. The surprising immune evasion ability of the omicron variant may bring many challenges to specific drug [ 31 ] . Paxlovid, an oral drug, has received the FDA's emergency use authorization for treating COVID-19 patients. The efficacy of paxlovid in elderly patients infected with the omicron variant is still unclear. By analyzing the usage of paxlovid between the two groups, we found that the early viral clearance group used paxlovid more frequently than the late group. Our results also suggested that paxlovid can significantly reduce the nucleic acid shedding time. In addition, unused paxlovid was an independent risk factor for the nucleic acid shedding. To best know the efficacy of paxlovid in SARS-CoV-2 omicron, many clinical studies are still needed. Used of methylprednisolone was found to prolonged viral shedding time, but it was not an independent risk factor. Previous studies also demonstrated that corticosteroid uses prolonged the viral shedding time in SARS-CoV-2 patients [ 32 ] . Another research reported that the treatment of low-dose corticosteroid does not delay the viral shedding time [ 33 ] . Therefore, the immunosuppressive effect of methylprednisolone may lead to the prolongation of the viral shedding time. However, this does not deny the therapeutic effect of methylprednisolone in COVID-19. There are several limitations of this study. 1) Our trial is a single study with small sample size; 2) We adopted to explore the risk factors associated with the viral shedding time, but not everyone was diagnosed on the first day; 3) There is no specific distinction in this article as to whether to vaccinate the booster vaccine. 4) Participants were only patients aged 60. Thus, the results presented in the manuscript can only represent this part of the population but not all patients infected with omicron; 5) This article only shows that the vaccine still has an effective on the viral shedding time of omicron, but it can not explain whether it can improve the severe condition and reduce the transmission of omicron; 6) This study can only explain the relationship between paxlovid and the viral shedding time, but can not explain the effective on the severe rate and mortality. With a larger sample, future trials may further help to clarify the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron. Conclusion This study demonstrated that age, D-dimer, methylprednisolone, and longer time from onset to enrollment could prolonged duration of viral shedding in older people infected with omicron. Moreover, time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron associated with viral shedding. Therefore, symptomatic patients with omicron should be hospitalized promptly and the indications for methylprednisolone therapy strictly controlled. In addition, the efficacy of paxlovid and vaccination in SARS-CoV-2 omicron should be further improved. Abbreviations COVID-19: Coronavirus Disease 2019; VOC: variants of concern; WHO: World Health Organization; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; FDA: Food and Drug Administration Declarations Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This trial received approval from the Ethics Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No. SH9H-2022-T112-2) and registered at the Chinese Clinical Trial Registry (ChiCTR2200060700). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Contributors W.Z., X.J., X.Y., Z.D., W.W., Z.S., W.Z., J.C., X.Y and Y.L. collected the epidemiological and clinical data. J.X. and Y.L. were responsible for enrollment and clinical monitoring. X.Y., W.C., Z.D., X.J. and Y.L. were responsible for the distribution and storage of medicines. W.Z., J.C., W.C., X.Y., Y.L. and X.J. were responsible for statistical data. X.Y., W.Z., X.J., X.Y., J.C., J.X. and Y.L. drafted the manuscript. J.C. and Y.L. were responsible for funding, study conception and design, revising and submitting the final manuscript. Acknowledgments We respectfully thank all patients enrolled in this study. This work was supported by the Fund for talent construction and scientific research of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. None of the individuals received compensation for their contribution. Role of the Funder/Sponsor The funding agencies had no role in the study design and clinical medications; collection, analysis, and interpretation of the data; preparation, written, review, or approval of the manuscript. References O'Neill L, Chumbler NR. Risk Factors for COVID-19 Hospitalization in School-Age Children. Health services research and managerial epidemiology. 2022;9:23333928221104677. Qin Z, Sun Y, Zhang J, Zhou L, Chen Y, Huang C. Lessons from SARS–CoV–2 and its variants (Review). Molecular medicine reports. 2022;26(2). Zhang J, Chen N, Zhao D, Zhang J, Hu Z, Tao Z. 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Cogliati Dezza F, Oliva A, Cancelli F, Savelloni G, Valeri S, Mauro V, et al. Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection. Diagnostic microbiology and infectious disease. 2021;100(2):115347. Zhou M, Yu FF, Tan L, Zhu YD, Ma N, Song LJ, et al. Clinical characteristics associated with long-term viral shedding in patients with coronavirus disease 2019. American journal of translational research. 2020;12(10):6954–64. Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, et al. Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. The European respiratory journal. 2020;56(1). Zhou C, Zhang T, Ren H, Sun S, Yu X, Sheng J, et al. Impact of age on duration of viral RNA shedding in patients with COVID-19. Aging. 2020;12(22):22399–404. Hu F, Yin G, Chen Y, Song J, Ye M, Liu J, et al. Corticosteroid, oseltamivir and delayed admission are independent risk factors for prolonged viral shedding in patients with Coronavirus Disease 2019. The clinical respiratory journal. 2020;14(11):1067–75. Fox-Lewis A, Fox-Lewis S, Beaumont J, Drinković D, Harrower J, Howe K, et al. SARS-CoV-2 viral load dynamics and real-time RT-PCR cycle threshold interpretation in symptomatic non-hospitalised individuals in New Zealand: a multicentre cross sectional observational study. Pathology. 2021;53(4):530–5. Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. Jama. 2020;324(5):460–70. Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychotherapy and psychosomatics. 2022;91(1):8–35. Feng Q, Wang Z, Yu H, Shi L, Xu L. [Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant]. Zhonghua wei zhong bing ji jiu yi xue. 2022;34(5):459–64. Fan Y, Li X, Zhang L, Wan S, Zhang L, Zhou F. SARS-CoV-2 Omicron variant: recent progress and future perspectives. Signal transduction and targeted therapy. 2022;7(1):141. Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19). Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020;71(15):799–806. Bennasrallah C, Zemni I, Dhouib W, Sriha H, Mezhoud N, Bouslama S, et al. Factors associated with a prolonged negative conversion of viral RNA in patients with COVID-19. International journal of infectious diseases: IJID : official publication of the International Society for Infectious Diseases. 2021;105:463–9. Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. The Journal of infection. 2020;80(6):e14-e8. Rössler A, Riepler L, Bante D, von Laer D, Kimpel J. SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons. The New England journal of medicine. 2022;386(7):698–700. Hu Z, Li S, Yang A, Li W, Xiong X, Hu J, et al. Delayed hospital admission and high-dose corticosteroids potentially prolong SARS-CoV-2 RNA detection duration of patients with COVID-19. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2021;40(4):841–8. Fang X, Mei Q, Yang T, Li L, Wang Y, Tong F, et al. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. The Journal of infection. 2020;81(1):147–78. Additional Declarations No competing interests reported. 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People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaosheng","middleName":"","lastName":"Yang","suffix":""},{"id":130574316,"identity":"f6c933b8-4d2d-4637-9a9d-6382cccb39c0","order_by":2,"name":"Xiufeng Jiang","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiufeng","middleName":"","lastName":"Jiang","suffix":""},{"id":130574317,"identity":"4f6eda0d-fac1-403b-8abd-1becbb4ac8b5","order_by":3,"name":"Zhixin Duan","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhixin","middleName":"","lastName":"Duan","suffix":""},{"id":130574318,"identity":"bc9b11e8-32c1-49ce-95a9-6c7212b820b8","order_by":4,"name":"Wei Wang","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wang","suffix":""},{"id":130574319,"identity":"35a7de5a-c4e3-4535-990e-c1c6742795ba","order_by":5,"name":"Zhaoliang Sun","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhaoliang","middleName":"","lastName":"Sun","suffix":""},{"id":130574320,"identity":"7ed3e0bf-67ef-418d-ae09-27308e79e9fd","order_by":6,"name":"Wanghao Chen","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wanghao","middleName":"","lastName":"Chen","suffix":""},{"id":130574321,"identity":"d77c7c57-51aa-49c9-b715-181e3853e9cd","order_by":7,"name":"Wenchuan Zhang","email":"","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of 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medicine","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Cheng","suffix":""},{"id":130574325,"identity":"93e8d428-0f18-48a9-b540-80668c2567ca","order_by":11,"name":"Yi Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYJCCAw8KJBjY2BsbH34gWkuCAVALz+FmYwmirUkwABIS6W0CPMSolp/d/BBoi0Vin+TDNgYJBjs53QYCWgzuHDMAOSyxTTqx7UEBQ7Kx2QFCWiQS4FragV46kLiNkBb5GekfIFokD7ZJ8BCjheFGDtQWCUYitRjcyCkAaTFu40kEBrIBEX4BOmzzhw8VdbLz248/fPihwk6OoBYYcGyAWEqkchCwJ0HtKBgFo2AUjDQAADRNQyGgXcrqAAAAAElFTkSuQmCC","orcid":"","institution":"Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yi","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2022-08-20 10:29:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1980808/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1980808/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":25619749,"identity":"2297f196-f0d5-4887-a48e-cec1a1db15f4","added_by":"auto","created_at":"2022-08-24 16:53:14","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":112468,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patients with confirmed SARS-CoV-2 omicron variant included in this study.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1980808/v1/7efd89feb4816165fbb457d6.jpg"},{"id":25619750,"identity":"2f3d3eda-4a22-4b5a-a972-040b36518e25","added_by":"auto","created_at":"2022-08-24 16:53:14","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":124011,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e Cumulative proportion of the nucleic acid shedding after illness onset by age (log-rank \u003cem\u003eP\u003c/em\u003e＜0.0001);\u003cstrong\u003e B.\u003c/strong\u003e Cumulative proportion of the nucleic acid shedding after illness onset between patients admitted to the hospital＜3 days and those admitted ≥3 days after illness onset (log-rank \u003cem\u003eP\u003c/em\u003e = 0.00012); \u003cstrong\u003eC. \u003c/strong\u003eCumulative proportion of the nucleic acid shedding after illness onset between Paxlovid patients or not (log-rank\u003cem\u003e P\u003c/em\u003e = 0.006).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1980808/v1/02ae52d613131f666cf00e1d.jpg"},{"id":27502218,"identity":"a15696a6-fe1e-4a15-b7f9-3922d908fbaf","added_by":"auto","created_at":"2022-10-08 13:14:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":596487,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1980808/v1/19d72af7-3d94-4462-ac83-4ac3b09e59b5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCoronavirus Disease 2019 (COVID-19) was identified in January 2020 and has been swept by human‑to‑human transmission \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Five variants of concern (VOC) have been identified so far, namely Alpha, Beta, Gamma, Delta, and Omicron variants designated by the World Health Organization (WHO) \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The rapid spread of the omicron variant was first identified on November 24, 2021, and became the predominant variant, posing a severe threat worldwide \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Compared to DNA viruses, RNA viruses have a higher mutation \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. During the COVID-19 pandemic \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, researchers indicated that the variant of omicron is the most mutated strain in the midst of SARS-CoV-2 variants, which may help the virus evade infection-blocking antibodies \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. These mutations will affect the characteristics of the SARS-CoV-2 omicron, including infectivity, immune escape, viral shedding time, and outcome. Data showed that the infectivity of SARS-CoV-2 omicron variants 10-fold higher than that of the original virus, but they were less likely to be admitted and require ICU level care \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. In addition, reinfection was observed approximately 10 times more frequently than in the Delta variant \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Therefore, omicron will significantly impact the therapeutic effect of COVID-19 drugs, immunity secondary to vaccination or prior infection, infectivity, and outcome \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn 2022, a wave of COVID-19 rapidly appeared in shanghai, China. After comparing the genomes of viruses, it was found that the genomes of the infected viruses in Shanghai belong to the Omicron BA.2.2 \u003csup\u003e[14, 15,]\u003c/sup\u003e. Zhang et al. found that the total cases in Shanghai were higher while the severity rate and mortality was lower, similar to other countries \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Moreover, studies of people infected with omicron variant suggested that older age might potentially predict mortality and severity \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eUnderstanding the kinetics of infectious viral shedding to possible transmission risk is crucial to guiding infection prevention and control strategies \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Therefore, it is essential to understand the shedding time of the variant of omicron since it is a crucial factor in the guidance of decisions about isolation precaution and antiviral treatment \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Through a retrospective cohort study, including 59 hospitalized patients with COVID-19, the elderly was independently associated with long-term virus shedding \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Another study demonstrated that sex, corticosteroid, and Delayed admission is an independent risk factor for prolonged virus shedding time in COVID-19 patients \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. However, whether these findings are also applicable to the omicron variants is still unclear. Up to June 24, 2022, we have used the search terms (\"Omicron\") and (\"shedding time\") and (\"prolonged\") to search PubMed and found no relevant articles. In short, the relationship between omicron viral shedding time and risk factors has not been fully clarified. Hence, this study aimed to evaluate the characteristics of viral shedding time with older patients infected with omicron and identify risk factors influencing the duration of viral shedding.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePatients enrollment\u003c/h2\u003e\n\u003cp\u003e361 participants with confirmed SARS-CoV-2 Omicron BA.2.2 admitted to the Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled for analysis. (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Participants were diagnosed with SARS-CoV-2 according to the guidelines of China (version 9). The earliest patient was admitted on April 23, 2020.\u003c/p\u003e\n\u003cp\u003eAccording to the characteristics of SARS-CoV-2 omicron, older patients are a risk factor for exacerbation of the disease. Hence, this study was aim to explore the occurrence of the viral shedding in older patients infected with omicron variants. Inclusion criteria: 1) Ct value\u0026lt;35 for both ORF1ab and N gene; 2) age\u0026thinsp;\u0026ge;\u0026thinsp;60. According to the criteria, 180 patients were enrolled. Among all patients, the viral shedding time of 88 patients was within 10 days, and that of 92 patients was over 10 days.\u003c/p\u003e\n\u003cp\u003eThis trial received approval from the Ethics Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No. SH9H-2022-T112-2) and registered at the Chinese Clinical Trial Registry (ChiCTR2200060700).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eTrial procedures\u003c/h2\u003e\n\u003cp\u003eThis retrospective cohort study was designed to assess the time of virus shedding in elderly participants infected with SARS-CoV-2 omicron (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003ePatients whose viral shedding time was less than 10 days were included in the early viral clearance group, and patients whose viral shedding time was more than or equal to 10 days were included in the late viral clearance group. Clinical characteristics and treatment of patients were collected using electronic medical records. The clinical characteristics were as follows: 1) age, mean; 2) cycle threshold value (CT. N and ORF); 3) time from onset to enrollment in patients; 4) gender; 5) condition at admission; 6) vaccine status; 7) comorbidity; 8) first symptoms; 9) laboratory indicators 10) time from the first admission to the negative testing; 11) viral shedding time. The treatment of patients was as follows: 1) medication; 2) auxiliary breathing; 3) whether to enter ICU.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eDefinition\u003c/h2\u003e\n\u003cp\u003eNucleic acid negative test is recognized as viral shedding (two consecutive, Ct value༞35 for the ORF and N gene) and was quantified by RT-PCR \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The time to viral shedding was from the first positive nucleic acid test to successive negative detection. Time from onset to patient enrollment was considered the time from the first positive nucleic acid test to the date of first hospitalization \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eConditions at admission were included: 1) asymptomatic cases; 2) mild cases; 3) moderate cases; 4) severe cases, according to Chinese guidelines (version 9). Charlson comorbidity index is a widely used complication scoring system involving 17 diseases \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Medication is the therapeutic drugs used during hospitalization, including paxlovid, anticoagulation, methylprednisolone, and Chinese medicine. Assisted breathing includes nasal tube oxygen inhalation, mask oxygen inhalation, ventilator oxygen inhalation, and ECMO.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eCategorical variables were described as numbers (%), and continuous variables were described as median (IQR) or mean (Standard Deviation, SD). Continuous variables were compared with the Mann-Whitney U test or Student's t test, and categorical variables were compared by the \u0026chi;\u0026sup2; test or Fisher's exact tests. Logistic regression was employed to analysis risk factors, adjusted odds ratio (OR and 95%CI were calculated. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant). The different rate of negative nucleic acid test between-group was compared by the Kaplan-Meier method with a log-rank test.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003eCharacteristics of participants in this trial\u003c/h2\u003e\n \u003cp\u003eThe study included 180 older participants infected with the variants of omicron. Among 180 participants, the median time of viral shedding was 10 days, and 104 (57.78%) were female with the mean age was 77.02. Among all patients, the median time from onset to enrollment was 1 day (1\u0026ndash;3 days), and the viral shedding time was 10 days (8\u0026ndash;12 days). Most patients were mild cases, and only 1 case (0.56%) was diagnosed as severe cases. Among the 180 patients, 56 (31.11%) were vaccinated, and 124 (68.89%) were unvaccinated. During hospitalization, 174 (96.67%) patients were treated with traditional Chinese medicine, followed by 134 (74.44%) patients treated with paxlovid. In addition, 28 (15.56%) patients needed nasal catheter assisted oxygen inhalation during hospitalization.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec9\"\u003e\n \u003ch2\u003eRisk factors for the viral shedding\u003c/h2\u003e\n \u003cp\u003eThe purpose of this study was to observe the virus shedding time of elderly patients infected with SARS-CoV-2 omicron. Then, Participants were further divided into two groups; one was the viral shedding time＜10 days (n\u0026thinsp;=\u0026thinsp;88), and another was the viral shedding time\u0026thinsp;\u0026ge;\u0026thinsp;10 days (n\u0026thinsp;=\u0026thinsp;92). Clinical characteristics, epidemiological, treatment, laboratory indicators, and outcomes were compared between either (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). No significant differences were found in the Ct value, or sex, between either group. Variables with statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between two groups, including age (75.05 vs. 78.91, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), vaccinated [38 (43.18%) vs. 18 (19.57%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001)], D-dimer (0.48 vs. 0.97, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030), time from onset to enrollment (1 vs. 3, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and time from the first day admission to the negative testing (6.18 vs. 8.7, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Compared with the late viral clearance group, the early viral clearance group had more patients using paxlovid [74 (84.09%) vs. 60 (65.22), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). However, patients who used methylprednisolone were higher in the late viral clearance group than in the early [6 (6.81%) vs. 15 (16.30%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048)]. In addition, the ratio of severe cases at first hospitalization in the late group was higher than that in the early group (0% vs. 1.09%), but no significant differences were found in the condition at admission. Moreover, we found that the mean of Charlson was higher in the late viral clearance group (0.76 vs. 1.09, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.051).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of clinical characteristics and treatment responses between groups with different viral shedding time\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;180\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eViral shedding time\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e＜10 days\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;88\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10days\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;92\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, mean (SD), year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.02 (9.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.05 (9.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.91 (9.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT.N, mean (SD) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.80 (2.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.50 (2.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.06 (2.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT.ORF, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.18 (3.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.72 (3.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.71 (3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from onset to enrollment in patients, median (IQR), day \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from the first day treatment to the negative testing, mean (SD), day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.47 (2.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.18 (1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.7 (2.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.515\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (42.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35 (39.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (44.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104 (57.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (60.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (55.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCondition at admission \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsymptomatic cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (6.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (10.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (3.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emild cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142 (78.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (76.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75 (81.52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emoderate cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (13.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (13.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (14.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esevere cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaccine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnvaccinated, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124 (68.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (56.82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (80.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evaccinated, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56 (31.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (43.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (19.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110 (61.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (60.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57 (61.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (22.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (17.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (28.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCoronary artery disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (17.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (21.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (14.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCharlson, median(IQR)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0\u0026ndash;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFever n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84 (46.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43 (48.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (45.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFatigue, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (27.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (22.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCough, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141 (78.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75 (81.52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExpectoration, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109 (60.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52 (59.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57 (61.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.694\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erunny nose, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56 (31.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (27.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (34.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSore throat, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64 (35.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (44.32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (27.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory indicators\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC, mean (SD), /L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.95 (1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.71 (1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.18 (1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL, mean (SD), /L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32 (0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.25 (0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.39 (0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT, median (IQR), U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (12.25-25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.78 (13-27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.15 (12\u0026ndash;25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST, median (IQR), U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.50 (22\u0026ndash;33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (21.5\u0026ndash;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.40 (23\u0026ndash;33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.547\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProthrombin time, mean (SD), s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.98 (0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.98 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.98 (0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.711\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.841\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAPTT, mean (SD), s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.43 (3.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.09 (2.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.76 (3.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFibrinogen, mean (SD), g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.20 (0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.09 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.30 (0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFibrinogen＜2, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (16.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (10.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (21.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer, mean (SD), mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43 (0.26\u0026ndash;0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.21\u0026ndash;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 (0.28\u0026ndash;0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer＞0.5, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (30.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (48.91%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP, mean (SD), mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.44 (2.28\u0026ndash;13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.49 (2.07\u0026ndash;10.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.9 (2.36\u0026ndash;15.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.229\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP＞10, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56 (31.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (27.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (34.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNasal duct, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (15.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (13.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (17.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePaxlovid, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134 (74.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (84.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 (65.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (17.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (12.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (22.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMethylprednisolone, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (11.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (6.81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (16.30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChinese medicine, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e174 (96.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (97.73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88 (95.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e* Indicated U test. \u003csup\u003ea\u003c/sup\u003e Real-time PCR Ct value. \u003csup\u003eb\u003c/sup\u003e Time from onset to enrollment in patients, including the time of initial symptoms or the first positive nucleic acid. \u003csup\u003ec\u003c/sup\u003e According to WHO criteria. \u003csup\u003ed\u003c/sup\u003e Charlson comorbidity index.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec10\"\u003e\n \u003ch2\u003eFactors associated with the shedding time\u003c/h2\u003e\n \u003cp\u003eVariables with statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between two groups, including vaccination status, age, time from onset to enrollment, use of paxlovid, use of methylprednisolone, D-dimer, and Charlson, were tested. The results showed that the vaccinated (OR, 0.319 [95% CI, 0.130\u0026ndash;0.786], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), used paxlovid (OR, 0.259 [95% CI, 0.104\u0026ndash;0.643], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), time from onset to enrollment (OR, 1.802 [95% CI, 1.391\u0026ndash;2.355], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000), and D-dimer (OR, 2.005 [95% CI, 0.975\u0026ndash;4.121], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.059) were independent factors associated with the time of viral shedding (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Kaplan Meier curve analysis indicated the cumulative viral negative proportion was higher in patients admitted to hospital within 3 days after the first nucleic acid positive (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). Moreover, patients in the vaccinated group had a higher probability of faster virus shedding than the unvaccinated group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). SARS-CoV-2 omicron clearance was delayed in participants who did not use paxlovid during hospitalization compared with those who used paxlovid (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariable analyses of factors associated with duration of viral shedding time\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eMultivariable analysis\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds ratio (OR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.983\u0026ndash;1.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.246\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaccinated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.130\u0026ndash;0.786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from onset to enrollment in patients, days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.391\u0026ndash;2.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePaxlovid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.104\u0026ndash;0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMethylprednisolone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.713\u0026ndash;8.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.975\u0026ndash;4.121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCharlson\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.928\u0026ndash;1.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003eClinical characteristics related to Paxlovid and vaccination status\u003c/h2\u003e\n \u003cp\u003eThere were 56 patients vaccinated, and 124 were unvaccinated (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). We did not found significant difference after compared to the two groups. However, the time from the first-day admission to the negative testing was prolonged in the unvaccinated group (7.85 vs. 6.62, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). During our study, 134 patients were treated with paxlovid, and 46 patients were not used. Participant characteristics were similar between the two groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Not using paxlovid group and using paxlovid group was significantly associated with the time from the first-day admission to the negative testing (8.26 vs. 7.19, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of clinical characteristics between groups of vaccine status or paxlovid status.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eVaccine status\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePaxlovid\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUnvaccinated\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;124\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaccinated\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;56\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUnused\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;46\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUsed\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;134\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, mean (SD), year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.79 (9.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.11 (8.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.20 (9.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.96 (9.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (38.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (39.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (61.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (60.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCondition at admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.696\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.675\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsymptomatic cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (7.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (7.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (8.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emild cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102 (82.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 (87.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (84.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e112 (83.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emoderate cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (9.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (10.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (7.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esevere cases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT.N, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.79 (2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.79 (2.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.20 (2.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.65 (2.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT.ORF, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.32 (3.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.03 (3.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.79 (3.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.04 (3.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from onset to enrollment in patients, median (IQR), day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1-3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.340\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCharlson, median(IQR)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0-1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0\u0026ndash;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0. 843\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC, mean (SD), /L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.93 (1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.22 (1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.86 (1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL, mean (SD), /L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.30 (0.90\u0026ndash;1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.25 (1-1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.960\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.30 (1-1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.20 (0.90\u0026ndash;1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer, mean (SD), mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 (0.28\u0026ndash;0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37 (0.21\u0026ndash;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.27\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (0.25\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWB＜4.0, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (27.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (19.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (29.10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL＞1.0, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (33.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (30.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (30.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (32.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer＞0.5, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (44.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (30.91%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (45.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (38.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP＞10, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (27.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (32.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (30.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eViral shedding time, mean (SD), day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.76 (3.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.95 (2.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.48 (3.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.75 (3.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from the first day treatment to the negative testing, mean (SD), day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.85 (2.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.62 (1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.26 (2.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.19 (2.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere are few investigation of the omicron variant shedding time. To the best of our knowledge, this retrospective trial aims to evaluate the risk factors associated with the time of viral shedding in the elder Chinese participants infected with omicron (age\u0026thinsp;\u0026ge;\u0026thinsp;60). We found that age, methylprednisolone therapy, longer time from onset to admission and D-dimer were associated with prolonged viral shedding. Moreover, results indicated that time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMany mutation changes were found across the omicron, significantly impacting the immunity secondary to vaccination or prior infection and the efficacy of therapeutic drugs \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Unvaccinated patients had a longer viral shedding time than vaccinated patients with SARS-CoV-2 omicron in our study [38 (43.18%) vs. 18 (19.57%)]. This observation may demonstrate that the vaccine has a role in accelerating the virus shedding of elderly patients infected with omicron. The findings are consistent with a prospective, observational study, which indicated that the vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients infected with omicron \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Like this research, Fan et al. proposed that the vaccine can provide effective protection against the variants of omicron, although there will be a percentage of breakthrough infections \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. However, our results only show that the vaccine can shorten the viral shedding time in this population. It can not be explained whether it can improve the severe disease rate and reduce the infection rate.\u003c/p\u003e \u003cp\u003eIn previous research, a study to observe the factors associated with viral shedding among a cohort of COVID-19 patients indicated that male participants had longer viral shedding and more severe symptoms than females infected with COVID-19 \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Unlike their results, we found no difference between gender and viral shedding time in patients with omicron. This result is consistent with a recent study \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Among the 180 patients, the mean age was 77.02 years. We found that older age could prolonged duration of viral shedding. It might be related to age-related comorbidities that may result in prolonged viral shedding \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. In the analysis of complications, we found differences in charlson comorbidity index between either group, but there was no significant difference in hypertension, diabetes, or chronic lung disease between them. We considered that the reason for this phenomenon is that the patients we included are older, so the proportion of patients with complications is higher than the average level. Therefore, the impact of a single comorbidity is relatively weak. We also found that a long time from onset to admission could also prolonged duration of viral shedding.\u003c/p\u003e \u003cp\u003eThe surprising immune evasion ability of the omicron variant may bring many challenges to specific drug \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. Paxlovid, an oral drug, has received the FDA's emergency use authorization for treating COVID-19 patients. The efficacy of paxlovid in elderly patients infected with the omicron variant is still unclear. By analyzing the usage of paxlovid between the two groups, we found that the early viral clearance group used paxlovid more frequently than the late group. Our results also suggested that paxlovid can significantly reduce the nucleic acid shedding time. In addition, unused paxlovid was an independent risk factor for the nucleic acid shedding. To best know the efficacy of paxlovid in SARS-CoV-2 omicron, many clinical studies are still needed. Used of methylprednisolone was found to prolonged viral shedding time, but it was not an independent risk factor. Previous studies also demonstrated that corticosteroid uses prolonged the viral shedding time in SARS-CoV-2 patients \u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. Another research reported that the treatment of low-dose corticosteroid does not delay the viral shedding time \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. Therefore, the immunosuppressive effect of methylprednisolone may lead to the prolongation of the viral shedding time. However, this does not deny the therapeutic effect of methylprednisolone in COVID-19.\u003c/p\u003e \u003cp\u003eThere are several limitations of this study. 1) Our trial is a single study with small sample size; 2) We adopted to explore the risk factors associated with the viral shedding time, but not everyone was diagnosed on the first day; 3) There is no specific distinction in this article as to whether to vaccinate the booster vaccine. 4) Participants were only patients aged 60. Thus, the results presented in the manuscript can only represent this part of the population but not all patients infected with omicron; 5) This article only shows that the vaccine still has an effective on the viral shedding time of omicron, but it can not explain whether it can improve the severe condition and reduce the transmission of omicron; 6) This study can only explain the relationship between paxlovid and the viral shedding time, but can not explain the effective on the severe rate and mortality. With a larger sample, future trials may further help to clarify the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrated that age, D-dimer, methylprednisolone, and longer time from onset to enrollment could prolonged duration of viral shedding in older people infected with omicron. Moreover, time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron associated with viral shedding. Therefore, symptomatic patients with omicron should be hospitalized promptly and the indications for methylprednisolone therapy strictly controlled. In addition, the efficacy of paxlovid and vaccination in SARS-CoV-2 omicron should be further improved.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOVID-19: Coronavirus Disease 2019; VOC: variants of concern; WHO: World Health Organization; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; FDA: Food and Drug Administration\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial received approval from the Ethics Committee of the Ninth People\u0026apos;s Hospital, Shanghai Jiao Tong University School of Medicine (No. SH9H-2022-T112-2) and registered at the Chinese Clinical Trial Registry (ChiCTR2200060700).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eW.Z., X.J., X.Y., Z.D., W.W., Z.S., W.Z., J.C., X.Y and Y.L. collected the epidemiological and clinical data. J.X. and Y.L. were responsible for enrollment and clinical monitoring. X.Y., W.C., Z.D., X.J. and Y.L. were responsible for the distribution and storage of medicines. W.Z., J.C., W.C., X.Y., Y.L. and X.J. were responsible for statistical data. X.Y., W.Z., X.J., X.Y., J.C., J.X. and Y.L. drafted the manuscript. J.C. and Y.L. were responsible for funding, study conception and design, revising and submitting the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe respectfully thank all patients enrolled in this study. This work was supported by the Fund for talent construction and scientific research of the Ninth People\u0026rsquo;s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. None of the individuals received compensation for their contribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the Funder/Sponsor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe funding agencies had no role in the study design and clinical medications; collection, analysis, and interpretation of the data; preparation, written, review, or approval of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eO'Neill L, Chumbler NR. Risk Factors for COVID-19 Hospitalization in School-Age Children. Health services research and managerial epidemiology. 2022;9:23333928221104677.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin Z, Sun Y, Zhang J, Zhou L, Chen Y, Huang C. Lessons from SARS\u0026ndash;CoV\u0026ndash;2 and its variants (Review). Molecular medicine reports. 2022;26(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang J, Chen N, Zhao D, Zhang J, Hu Z, Tao Z. 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[Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant]. Zhonghua wei zhong bing ji jiu yi xue. 2022;34(5):459\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan Y, Li X, Zhang L, Wan S, Zhang L, Zhou F. SARS-CoV-2 Omicron variant: recent progress and future perspectives. Signal transduction and targeted therapy. 2022;7(1):141.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19). Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020;71(15):799\u0026ndash;806.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBennasrallah C, Zemni I, Dhouib W, Sriha H, Mezhoud N, Bouslama S, et al. 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The Journal of infection. 2020;81(1):147\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"viral shedding time, SARS-CoV-2, Omicron, factors","lastPublishedDoi":"10.21203/rs.3.rs-1980808/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1980808/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo explore the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eParticipants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to the shedding time of omicron [\u0026ge;\u0026thinsp;10 days, \"late clearance group\" and \u0026lt;\u0026thinsp;10 days, \"early clearance group\"].\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e180 patients were enrolled in the study (88 early, 92 late), with a median time of viral shedding was 10 days and a mean age of 77.02 years. When comparing patients between either group, prolonged SARS-CoV-2 omicron shedding was associated with old age (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), unvaccinated (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), delayed admission to hospital after illness onset (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), D-dimer (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) and methylprednisolone treatment (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). In the multivariable analysis, vaccinated [OR], 0.319 [95% CI, 0.130\u0026ndash;0.786], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), paxlovid (OR, 0.259 [95% CI, 0.104\u0026ndash;0.643], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), and time from onset to admission (OR, 1.802 [95% CI, 1.391\u0026ndash;2.355], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000) were significantly associated with viral clearance.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe older age, methylprednisolone therapy, and D-dimer were associated with prolonged duration of omicron viral shedding. The time from onset to hospitalization, unused paxlovid and unvaccinated were independent risk factors in patients infected with SARS-CoV-2 omicron.\u003c/p\u003e","manuscriptTitle":"Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-24 16:53:12","doi":"10.21203/rs.3.rs-1980808/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"52580bd4-c942-436a-840d-6524de19997f","owner":[],"postedDate":"August 24th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-08T13:14:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-24 16:53:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1980808","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1980808","identity":"rs-1980808","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}