Clinical Characteristics of COVID-19 Reinfection: A Retrospective Study in China

Clinical Characteristics of COVID-19 Reinfection: A Retrospective Study in China | 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 Clinical Characteristics of COVID-19 Reinfection: A Retrospective Study in China Chao-Chao Qiu, Xiao-Qing Lin, Qiang Zhang, Ya-Long Chen, Xiao-Qiao Su, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4193207/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Feb, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 16 You are reading this latest preprint version Abstract Purpose The number of patients with COVID-19 reinfection is gradually increasing.In this study, we aimed to investigate the clinical characteristics of individuals who experienced COVID-19 reinfection. Methods A retrospective data analysis was conducted involving patients diagnosed with COVID-19 between April 1, 2023, and June 20, 2023. The patients were categorized into two groups: the observation group, consisting of individuals with reinfection, and the control group, comprising those with primary infection. Results A Total 905(905/1025) patients were included in the study,with 407 in the observation group and 498 in the control group. The top three clinical symptoms in both groups were fever, cough with expectoration, and dizziness with fatigue ( p < 0.001). The clinical classification of patients in the observation group primarily consisted of non-severe cases, ( p <0.001). The proportion of hospitalized patients was lower in the observation group than in the control group ( p < 0.001). The observation group exhibited a shorter clinical symptom recovery time than that of the control group (median, 5 d vs. 7 d, p < 0.001). Conclusion Patients experiencing COVID-19 reinfection were primarily classified as non-severe cases, with lower proportions of occurrence of severe and rare critical conditions. The severity was milder compared to that in patients with primary COVID-19 infections. COVID-19 infection reinfection clinical symptoms clinical typing severity Omicron variant Figures Figure 1 Figure 2 1. Introduction Coronavirus disease 2019 (COVID-19), caused by a newly discovered coronavirus in recent years, has emerged as one of the three most severe coronavirus outbreaks, alongside the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2002 and Middle East respiratory syndrome coronavirus in 2012. Since its emergence in late 2019, COVID-19 has rapidly spread worldwide, with the cumulative number of infections exceeding hundreds of millions. With the continuous mutation of coronaviruses [ 1 ], the Omicron variant has gained rapid prominence globally since November 2021 [ 2 ], now establishing itself as the dominant strain in the ongoing pandemic [ 3 ]. Notably, the Omicron variant exhibits high transmissibility but significantly reduced pathogenicity compared to those of the original strain [ 4 , 5 ]. Furthermore, due to the mutability of Omicron's antigenic sites, it possesses a remarkably high capacity for immune evasion, posing a higher risk of reinfection to the population [ 6 ]. An analysis conducted by the UK Office for National Statistics on COVID-19 cases from July 2020 to November 2022 revealed the highest repeat infection rate of 16.6% [ 7 ]. Since December 2022, various regions in China have gradually lifted the treatment policy of isolation for individuals infected with COVID-19. However, the ongoing spread of COVID-19 infections has had severe impact on public health. In the aftermath of the infection peak, understanding the clinical characteristics of COVID-19 reinfection becomes crucial for adopting effective prevention and treatment strategies. Hence, in this study, we aimed to elucidate the clinical characteristics of individuals with COVID-19 reinfection by comparing them with those who experienced the primary COVID-19 infection within the same time period. 2. Methods 2.1.Study patients A retrospective data collection was undertaken, focusing on patients diagnosed with COVID-19 infection in Wenzhou between April 1, 2023, and June 20, 2023. Through careful adherence to predefined inclusion and exclusion criteria, patients were categorized into two groups based on whether they had experienced COVID-19 reinfection. The observation group included patients who had experienced reinfection, whereas the control group consisted of individuals who had experienced primary COVID-19 infection. Informed consent was obtained from all enrolled patients, who were duly informed and who voluntarily agreed to participate in the study. This study was approved by the Ethics Committee of Wenzhou Central Hospital of Zhejiang Province (approval number:L2023-03-022) in China. 2.2.Data collection Demographic characteristics was collected for the two groups of patients, including age, sex, medical history of underlying diseases, and vaccination history. Additionally, data on clinical classification; clinical symptoms (fever, myalgia, cough expectoration, dizziness, fatigue, loss or reduction of smell and taste, gastrointestinal symptoms [vomiting and diarrhea], chest tightness, shortness of breath, dry throat, sore throat, and sore eyes); laboratory tests (complete blood count and C-reactive protein [CRP] level); and recovery time, were collected.The information comes from the hospital's electronic medical records. 2.3.Selection criteria 2.3.1.Inclusion criteria : (1) Patients diagnosed with COVID-19 infection within the past 1 week, (2) aged ≥ 18 years, and (3) weight ≥ 40 kg. 2.3.2.Exclusion criteria : (1) Patients with concurrent influenza or other viral infections; (2) those with other serious organic diseases and an expected survival of < 1 month; (3) those with acute exacerbation of pulmonary diseases, such as asthma, bronchiectasis, and chronic obstructive pulmonary disease; (4) those who received antiviral medication within the last 1 week prior to enrollment; (5) those who is suspected or confirmed to have concurrent active systemic infection besides being infected with COVID-19; (6) those with known human immunodeficiency virus infection; (7) those who have had more than one instance of previous COVID-19 infections; and (8) pregnant or lactating women. 2.4.Diagnostic criteria The diagnosis of COVID-19 infection was established if the patients met the following two criteria [ 8 ]: exhibiting relevant clinical manifestations of COVID-19 infection and testing positive on either a COVID-19 nucleic acid test or COVID-19 antigen test. 2.5.Clinical typing Clinical typing was determined based on the severity classification of COVID-19 according to the World Health Organization (WHO) as follows [ 9 ].(1)Non-severe COVID − 19: defined as the absence of any criteria for severe or critical case of COVID-19. (2) Severe COVID-19: defined by any of the following criteria: 1) oxygen saturation 30 breaths per minute; in children, very severe chest wall indrawing, grunting, central cyanosis, or presence of any other general danger signs, including inability to breastfeed or drink, lethargy, convulsions, or reduced level of consciousness). (3) Critical COVID-19: defined by the criteria for acute respiratory distress syndrome, sepsis, septic shock, or other conditions that would normally require the provision of life-sustaining therapies, such as mechanical ventilation (invasive or non-invasive) or vasopressor therapy. 2.6.Hospitalization criteria The hospitalization criteria for this study were determined based on the clinical management guidelines for COVID-19 provided by the WHO [ 9 ] and other local policies, which are outlined as follows: Patients whose condition met any of the following criteria and are willing to be hospitalized are eligible for hospitalization: 1) Severe and critical cases. 2) Non-severe cases, but exhibiting prominent clinical symptoms, particularly chest tightness or respiratory distress, requiring oxygen therapy support. 3) Exacerbation of pre-existing underlying diseases that could not be controlled. 2.7.Treatment plan The treatment plan was based on the dynamic guidelines for pharmacotherapy of COVID-19 published by the WHO titled, “A living WHO guideline on drugs for COVID-19” [ 10 ]. The general principles are as follows: for non-severe patients, control supportive therapy is administered. Paxlovid is strongly recommended for individuals with high-risk factors who may require hospitalization, whereas molnupiravir, remdesivir, sotrovimab, and casirivimab/imdevimab are weakly recommended. For severe and critical patients, corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase inhibitor (baricitinib) are strongly recommended. 2.8.Statistical methods Data were processed using IBM SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, USA). Normality test and homogeneity of variance test were performed for measurement data. Normally distributed data were expressed as mean ± standard deviation (x ± s), whereas non-normally distributed data were presented as median and interquartile range (M[P25, P75]). Count data were described using frequency and percentage. For measurement data that met the normality and homogeneity of variance assumptions, the independent samples t-test was used for between-group comparisons. When these assumptions were not met, a non-parametric statistical test, the Mann Whitney U test, was used. The between-group comparison of count data was conducted using the chi-square test. A p value < 0.05 indicates a statistically significant difference. 3. Results 3.1.General conditions of enrolled patients In the present study, we initially collected data from a total of 1,025 patients who were diagnosed with COVID-19 infection in Wenzhou between April 1, 2023, and June 20, 2023. After applying the inclusion and exclusion criteria, 120 patients who did not meet the criteria were excluded. Consequently, 905 patients were included in the study, with 407 in the observation group and 498 in the control group. No significant differences in demographic characteristics were observed between the two groups ( p > 0.05), as presented in Table 1 . The comorbidity history of the patients included hypertension, diabetes, hepatitis B, tumor (stable stage), tuberculosis (stable stage), coronary heart disease (stable stage), rheumatic disease (stable stage), and others. Vaccination history encompassed any dose of COVID-19 vaccine (including adenovirus vector, inactivated, or recombinant protein vaccines) they had received. According to the Epidemic Control Center data, the prevalent regional epidemic strains of COVID-19 were the Omicron variants including, the XBB series (the most widespread), with its top three subvariants being XBB.1.9, XBB.1.16, and XBB.1.22, and their respective sub-branches. In the observation group, the time intervals between the reinfection and primary COVID-19 infection varied. Specifically, 6, 54, 304, 40, 1, 1, and 1 cases of reinfection occurred within an interval of 3, 4, 5, 6, 11, 12, and 14 months, respectively. The mean interval length was 5.06 ± 0.877 months, with a median of 5 months. Table 1 Comparison of the demographic characteristics between the two groups of patients. (n = 1,025) Feature Observation group (x ± s) Control group (x ± s) t/χ 2 p value Age `(years) 54.5 ± 19.6 53.7 ± 18.2 0.630 0.529 Sex 0.008 0.947 Male [number (%)] 199 (48.9%) 242 (48.6%) Female [number (%)] 208 (51.1%) 256 (51.4%) Medical history of underlying diseases [number (%)] 157 (38.6%) 211 (42.4%) 1.336 0.276 History of one disease 90 (22.1%) 134 (26.7%) History of two diseases 45 (11.1%) 52 (10.5%) History of three or more diseases 22 (5.4%) 26 (5.2%) History of vaccination [number (%)] 340 (83.5%) 432 (86.7%) 1.840 0.187 Note: All p values > 0.05. 3.2.Comparison of clinical symptoms between the two groups The differences in clinical symptoms between the two patient groups are presented in Table 2 . In the observation group, the top three clinical symptoms of COVID-19 were fever (318, 78.1%), cough with expectoration (300, 73.4%), and dizziness with fatigue (188, 46.2%). Similarly, in the control group, the top three clinical symptoms were fever (446, 89.6%), cough with expectoration (338, 67.9%), and dizziness with fatigue (197, 39.6%). The differences in the occurrence rates of clinical symptoms between the two groups were statistically significant (χ 2 = 113.537, p < 0.001). In this study, among the patients with fever in the observation (n = 318) and control (n = 446) groups, the median peak temperatures during the course of illness were 38.3°C (37.4°C–40.0°C) and 39°C (37.4°C–40.5°C), respectively. The difference in peak temperatures between the two groups was statistically significant (t = 14.210, p < 0.001). Table 2 Comparison of the clinical characteristics between the two groups of patients Clinical characteristics Observation group Control group t/χ 2 p value Clinical symptoms 113.537 <0.001 Fever [number (%)] 318 (78.1%) 446 (89.6%) 22.229 <0.001 Myalgia [number (%)] 107 (26.3%) 161 (32.3%) 3.919 0.049 Cough with expectoration [number (%)] 300 (73.4%) 338 (67.9%) 3.671 0.055 Dizziness with fatigue [number (%)] 188 (46.2%) 197 (39.6%) 4.032 0.050 Loss or reduced sense of smell and taste [number (%)]] 22 (5.4%) 43 (8.9%) 3.503 0.061 Gastrointestinal symptoms (vomiting, diarrhea) [number (%)] 52(12.8%) 59 (11.8%) 0.180 0.685 Chest tightness and shortness of breath [number (%)] 44 (10.8%) 144 (28.9%) 44.605 <0.001 Dry throat and sore throat [number (%)] 155 (38.1%) 180 (36.1%) 0.361 0.580 Sore eyes [number (%)] 22 (5.4%) 23 (4.6%) 0.294 0.646 Median peak temperature (°C) 38.3 (37.4–40.0) 39.0 (37.4–40.5) 14.210 <0.001 COVID-19 nucleic acid cycle threshold (CT) value N gene 28.46 ± 4.69 27.36 ± 5.49 2.542 0.011 ORF1a/b gene 29.19 ± 4.62 28.10 ± 5.62 2.480 0.013 Laboratory tests Leukocyte count [×10 9 /L] 5.94 ± 2.19 6.01 ± 2.37 0.321 0.748 C-reactive protein [mg/L] 10.90 ± 11.45 12.21 ± 12.76 1.016 0.310 Clinical classification 115.843 <0.001 Non-severe [number (%)] 344 (84.5%) 307 (61.7%) Severe [number (%)] 63 (15.5%) 185 (37.1%) Critical [number (%)] 0 (0%) 6 (1.2%) Hospitalization [number (%)] 58 (14.3%) 158 (31.7%) 37.644 <0.001 Duration of clinical symptom improvement (days) 5.45 ± 3.70 8.31 ± 4.55 10.209 <0.001 3.3.Comparison of the CT values of COVID-19 nucleic acid between the two groups Among the 905 enrolled patients, 320 and 585 were diagnosed with positive COVID-19 antigen and positive COVID-19 nucleic acid, respectively. In the observation and control groups, 244 and 341 patients had positive COVID-19 nucleic acid, respectively. The mean CT values of COVID-19 nucleic acid N gene were 28.76 ± 4.93 and 27.49 ± 5.61 in the observation and control groups, respectively. The difference in values for the COVID-19 nucleic acid N gene between the two groups was statistically significant (t = 2.542, p = 0.011). For the COVID-19 nucleic acid ORF gene, the observation and control groups exhibited mean values of 29.46 ± 4.82 and 28.76 ± 4.93, respectively. The difference in values for the COVID-19 nucleic acid ORF gene between the two groups was statistically significant (t = 2.480, p = 0.013), as presented in Table 2 . 3.4.Comparison of laboratory examination indicators between the two patient groups Among the 905 enrolled patients, 421 (observation group, n = 136; control group, n = 285) underwent routine blood and/or CRP examinations. The mean leukocyte counts in the observation and control groups were 5.94 ± 2.19 (×10 9 /L) and 6.01 ± 2.37 (×10 9 /L), respectively, demonstrating no significant difference between the two groups (t = 0.321, p = 0.748). Regarding CRP, the observation and control groups exhibited mean values of 10.90 ± 11.45 (mg/L) and 12.21 ± 12.76 (mg/L), respectively, demonstrating no significant difference between the two groups (t = 1.016, p = 0.310), as presented in Table 2 . 3.5.Comparison of severity between the two patient groups Using the WHO severity classification of COVID-19, the patients were categorized into different groups. In the observation group, out of 407 patients, 344, 63, and 0 were categorized as non-severe, severe, and critical cases. In contrast, out of 498 patients in the control group, 307, 185, and 6 were categorized as non-severe, severe, and critical cases, respectively. The differences were statistically significant between the two groups (χ 2 = 115.843, p < 0.001), as depicted in Fig. 1 . Regarding hospitalization, 58 (14.3%) and 158 (31.7%) patients required hospitalization in the observation and control groups, respectively, with statistically significant difference between the two groups (χ 2 = 37.644, p < 0.001), as presented in Table 2 . 3.6.Duration till clinical symptom improvement in the two groups Based on the WHO treatment approach, patients in both the groups received appropriate treatment. The duration till clinical symptom improvement in the observation and control groups ranged from 1 to 30 (mean duration, 5.45 ± 3.70) and 1 to 40 (mean duration, 8.31 ± 4.55) days, respectively, demonstrating statistically significant difference between the two groups (t = 10.209, p < 0.001), as presented in Table 2 . The distribution of the duration till clinical symptom improvement in the two groups is illustrated in Figs. 2 a and 2 b, respectively. 4. Discussion Over time, the SARS-CoV-2 has continued to evolve, giving rise to new variants of concern (VOC). The VOCs (including alpha, beta, gamma, delta, and Omicron) have demonstrated the virus’s ability to adapt to the host and evade host immune responses, thereby weakening the neutralizing efficacy of antibodies [ 11 , 12 ], leading to an elevated risk of reinfection with COVID-19. In late December 2022, China experienced a widespread outbreak of COVID-19, with most individuals experiencing primary infection. These individuals may now face the risk of developing reinfection with the SARS-CoV-2. The present study aimed to investigate the clinical characteristics of patients experiencing COVID-19 reinfection by comparing them with those who experienced primary infections during the same time period. In this study, patients experiencing COVID-19 reinfection developed infection at an interval of > 3 months since their primary infection. Over time, as the number of infections increased, the average interval became 5.06 ± 0.877 months, with a median of 5 months. This interval is shorter than what had been previously reported (> 200 days) [ 13 , 14 ], and may be attributed to the difference in study duration. Additionally, the changes in the circulating strains could have potentially influenced these results. A significant increase in the number of infections was observed in the fourth and fifth months after the primary infection, followed by a decrease after the 6-month interval. Liew et al. [ 15 ] also observed that nasal antibodies against the Omicron variant persisted for only 3–5 months, which could be an important factor contributing to repeated Omicron variant infections. Limited data on infections occurring beyond 6 months were identified in this study, possibly due to the relatively short timeframe since the gradual lifting of COVID-19 control policies in China, with most included patients experiencing COVID-19 reinfection in < 6 months of their primary infection. Therefore, further exploration is required to understand the data on COVID-19 reinfection occurring after an interval of 6 months. Furthermore, in accordance with the WHO’s definition of COVID-19 reinfection [ 16 ], all reinfection patients in this study occurred after an interval > 3 months since their primary infection. This finding demonstrated that they were indeed COVID-19 reinfection rather than instances of COVID-19 viral reactivation. In this study, the observation group exhibited proportions of 84.5% non-severe, 15.5% severe, and 0% critical cases in clinical classification. These proportions significantly differed from those in the control group, which had 61.7% non-severe, 37.1% severe, and 1.2% critical cases. These findings indicated that COVID-19 reinfection patients were predominantly non-severe, with a lower proportion of severe and rare occurrence of critical cases. Moreover, when comparing the hospitalization rates between the two patient groups, a significantly lower proportion of patients experiencing reinfection required hospitalization that that of patients experiencing primary COVID-19 infections. This suggested that the severity of COVID-19 reinfection patients is generally milder than that of primary infections. However, it should be noted that this study only included patients who actively sought medical care at the hospital, and a substantial number of patients with milder symptoms might not have visited the hospital, potentially leading to an underestimation of the proportion of non-severe cases and an overestimation of that of severe and critical cases. When comparing the clinical symptoms between the two groups, the top three clinical symptoms in both the groups (fever, cough with expectoration, and dizziness with fatigue) differed significantly, with a lower rate of fever evident in the observation group. In COVID-19 reinfection group, the primary clinical symptoms continued to be fever, cough with expectoration, dizziness with fatigue, dry throat, sore throat, and myalgia. However, the occurrence rate of fever symptoms was lower in COVID-19 reinfection group than in primary COVID-19 infection group; this contrasts with the findings of previous reports suggesting that approximately 85% of COVID-19 reinfection patients are asymptomatic [ 17 , 18 ]. The median highest body temperature for theCOVID-19 reinfection groups was 38.3°C, which was lower than that observed for the primary COVID-19 infections group (39.0°C), suggesting that fever symptoms are less severe in COVID-19 reinfection patients than in primary COVID-19 infection. The median duration for complete or substantial symptom improvement was 5 and 7 days for patients with reinfection and primary infections, respectively. Consequently, we inferred that patients experiencing COVID-19 reinfection recover from clinical symptoms at a faster rate than patients experiencing primary infections do. These findings align with the findings of West [ 19 ], who reported milder symptoms and faster recovery in cases of COVID-19 reinfection. In addition, the COVID-19 Forecasting Team [ 20 ] analyzed data from 65 studies across 19 different countries and reported that following a previous infection with the Omicron variant, the antibodies levels rapidly decline over time, leading to a rapid decrease in protection against reinfection with COVID-19. However, protection against severe cases continues for a relatively longer duration. This notion corresponds with the low proportion of severe and rare critical cases observed in the observation group in the present study. When comparing the CT values of the COVID-19 nucleic acid between the two groups, the observation group exhibited lower N gene and ORF gene values that those of the control group, indicating a lower viral load in patients experiencing COVID-19 reinfection than that of patients experiencing primary infections. This study had certain limitations. The different timing of patient visits and COVID-19 nucleic acid sampling after symptom onset might have affected the accuracy of the COVID-19 nucleic acid CT values in accurately reflecting the viral load at a specific moment after infection. 5. Conclusions Patients experiencing COVID-19 reinfection are primarily classified as having non-severe conditions, with a low proportion of occurrence of severe and rare critical conditions. Their severity is milder than that of patients experiencing primary COVID-19 infections. Additionally, the viral load is relatively lower, and the duration till clinical symptom recovery is shorter in patients experiencing reinfection. Furthermore, a lower proportion of these patients requires hospitalization. It can be seen that the condition of COVID-19 reinfection is relatively mild, and we do not need to be overly anxious and panic in the face of the COVID-19 reinfection. At the same time, we should not completely ignore the harm caused by the COVID-19. Studies have found that with the increase of the number of the COVID-19 infections, the risk of all-cause mortality and adverse health consequences will also increase [ 21 ]. We should treat the COVID-19 infection rationally, and in the face of the COVID-19 reinfection, we should not worry too much, but also do a good job of personal protection. Avoid repeated infection with the COVID-19. Abbreviations COVID-19：Coronavirus disease 2019；WHO：the World Health Organization. Declarations 7.1Ethics approval and consent to participate Informed consent was obtained from all enrolled patients, who were duly informed and who voluntarily agreed to participate in the study. This study was approved by the Ethics Committee of Wenzhou Central Hospital of Zhejiang Province (approval number:L2023-03-022) in China. 7.2. Consent for publication Not applicable in this section. 7.3. Availability of data and materials The datasets generated and analysed during the current study are not publicly available due to protect study participant privacy but are available from the corresponding author on reasonable request. 7.4. Competing interests The authors declare that they have no competing interests. 7.5. Funding No funding. 7.6. Authors' contributions C.C.Q. and X.G.J . were involved in the conception and design. Q.Z., Y.L.C, X.Q.S., M.Y.Z., L.F.Z, F.C., S.R.X. and L.F.Z. collected the data. X.Q.L.were involved in the analysis and interpretation of the data. Z.R.L.,F.C and S.R.X searched, sorted, and interpreted the relevant literature. C.C.Q.and J.C.S.were involved in the drafting of the paper, revising it critically for intellectual content. All authors edited and approved the final manuscript and agree to be accountable for all aspects of the work. References Gobeil S-M, Henderson R, Stalls V, et al. Structural diversity of the SARS-CoV-2 Omicron spike. Molecular Cell, 2022, 82(11):2050-2068. DOI：10.1101/2022.01.25.477784. El-Shabasy RM, Nayel MA, Taher MM, Abdelmonem R, Shoueir KR, Kenawy ER,et al.. Three waves changes, new variant strains, and vaccination effect against COVID-19 pandemic. Int J Biol Macromol. 2022 Apr 15;204:161-168. DOI: 10.1016/j.ijbiomac. Liu M, Zhang B-Y, Zhao L-H,et al.Pathogenesis and epidemiology of Omicron, a new coronavirus variant[J]. China Practical Medicine,2023,07:160-163. DOI：10.14163/j.cnki.11-5547/r.2023.07.044. Lu Y J,Okpani A I,McLeod C B,et al. Masking strategy to protect healthcare workers from COVID-19:An umbrella meta-analysis.[J]. Infection, disease & health,2023,01:2468-0869. DOI:10.1016/J.IDH.2023.01.004. Peng D-P,Xing X-Y,Wang Y,Zhang K-Y,Niu J Q,et al. Epidemiologic and clinical characteristics of a novel omicron variant of coronavirus[J]. Chinese Journal of Viral Diseases,2022,05:385-389. DOI：10.16505/j.2095-0136.2022.0058. Chen J, Wang R, Gilby NB, et al. Omicron variant (B.1.1.529): infectivity, vaccine breakthrough, and antibody resistance[J]. J Chem Inf Model, 2022, 62(2): 412 422. DOI: 10.1021/acs.jcim.1c01451. Satistics OFN. Coronavirus (COVID-19) Infection Survey, characteristics of people testing positive for COVID-19, UK. 2022 [EB/OL].(2022) Available at：https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/coronaviruscovid19infectionsinthecommunityinengland. Yahav D, Yelin D, Eckerle I, Eberhardt CS, Wang J, Cao B, Kaiser L. Definitions for coronavirus disease 2019 reinfection, relapse and PCR re-positivity. Clin Microbiol Infect. 2021 Mar;27(3):315-318. doi: 10.1016/j.cmi.2020.11.028. Epub 2020 Dec 5. World Health Organization. COVID-19 Clinical management: living guidance[EB/OL].(2023)Available at：https://www.who.int/teams/health-care-readiness/covid-19. World Health Organization. Update to living WHO guideline on drugs for covid-19.[J]. BMJ (Clinical research ed.),2023,380(57):1756-1833. DOI：10.1136/bmj.p57. GarciaBeltran W F, Lam E C, ST DENIS K, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity[J]. Cell, 2021,184(9):2372-2383. DOI:10.1016/J.CELL.2021.04.006. Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization[J]. Nature, 2021, 596(7871)：276-280. DOI:10.1038/S41586-021-03777-9. Bastard J, Taisne B, Figoni J, Mailles A, Durand J, Fayad M, Josset L, Maisa A, van der Werf S, Parent du Châtelet I, Bernard-Stoecklin S. Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022. Euro Surveill. 2022 Mar;27(13):2200247. DOI: 10.2807/1560-7917.ES.2022.27.13.2200247. Nguyen NN, Houhamdi L, Hoang VT, Delerce J, Delorme L, Colson P, Brouqui P, Fournier PE, Raoult D, Gautret P,et al. SARS-CoV-2 reinfection and COVID-19 severity. Emerg Microbes Infect. 2022 Dec;11(1):894-901. DOI: 10.1080/22221751.2022.2052358. Liew F, Talwar S, Cross A, Willett BJ, Scott S, et al.SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination[J].EBioMedicine,2023,87(1):2352-3964. DOI:10.1016/j.ebiom.2022.104402. Kumar V, Iyengar K, Garg R, Vaishya R,et al.. Elucidating reasons of COVID-19 re-infection and its management strategies. Diabetes Metab Syndr. 2021，15(3):1001-1006. DOI:10.1016/j.dsx.2021.05.008. Cohen C, Kleynhans J, von Gottberg A, et al. SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21. Lancet Infect Dis. 2022 Jun;22(6):821-834. doi: 10.1016/S1473-3099(22)00069-X. Borras-Bermejo B, Piñana M, Andrés C, et al. Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain. Front Microbiol. 2022 May 26;13:876409. DOI: 10.3389/fmicb.2022.876409. West Jack. Covid-19 reinfection-what could the absence of evidence suggest[J]. The Infect Dis, 2021,53(7):486-487. DOI:10.1080/23744235.2021.1910339. COVID-19 Forecasting Team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis[J]. The Lancet, 2023,401(10379):833-842. DOI：10.1016/S0140-6736(22)02465-5. Bowe Benjamin,Xie Yan,AlAly Ziyad. Acute and postacute sequelae associated with SARS-CoV-2 reinfection.[J]. Nature medicine,2022,28(11)：2398-2405. DOI：10.1038/s41591-022-02051-3. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Feb, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 17 Dec, 2024 Reviewers agreed at journal 15 Dec, 2024 Reviewers agreed at journal 14 Dec, 2024 Reviews received at journal 14 Dec, 2024 Reviews received at journal 14 Dec, 2024 Reviewers agreed at journal 14 Dec, 2024 Reviewers agreed at journal 13 Dec, 2024 Reviewers agreed at journal 13 Dec, 2024 Reviewers agreed at journal 13 Dec, 2024 Reviews received at journal 28 Sep, 2024 Reviewers agreed at journal 23 Sep, 2024 Reviewers invited by journal 23 Sep, 2024 Editor invited by journal 23 Aug, 2024 Editor assigned by journal 02 Apr, 2024 Submission checks completed at journal 02 Apr, 2024 First submitted to journal 30 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4193207","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":287247615,"identity":"05a59b37-e288-4bca-870c-36b766546c71","order_by":0,"name":"Chao-Chao Qiu","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chao-Chao","middleName":"","lastName":"Qiu","suffix":""},{"id":287247616,"identity":"05b93555-5486-45cc-9519-6c140a9d960a","order_by":1,"name":"Xiao-Qing Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBACPmYgkQDEbEBskFBhI8fG3n4ArxY2ZC0FD86kGfPxnEnArwWZ8/Fhy+HEeRIOBvi1sPMek3hQYyPbJ91+cUNiA3N6mwTQ1h8V2/A4jC/ZIOFYmnGbzJlig8QdbLlt0o0HGHvO3MajhcfwQQLb4cQ2iZw0g8QzPLltMgcSmBnb8GoxOJDwD6wl/QeQTGeTSDAgpMXwQWIbSEv6AYPENoMEYrQYGyT2Af0ikQOMlzMJhm3AQD6Izy/8/GfMJH98s5GdPyP9geGPiv/y8u3tBx/8qMCtBQYYGxh4ENFxgKB6iBb2B8QoHAWjYBSMghEIAHs7VcGFsuPxAAAAAElFTkSuQmCC","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xiao-Qing","middleName":"","lastName":"Lin","suffix":""},{"id":287247617,"identity":"04654af9-c9d5-451f-8a5e-a06edc41b879","order_by":2,"name":"Qiang Zhang","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Zhang","suffix":""},{"id":287247618,"identity":"d6f15080-8355-4c98-b649-a22dae99ec5d","order_by":3,"name":"Ya-Long Chen","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ya-Long","middleName":"","lastName":"Chen","suffix":""},{"id":287247619,"identity":"bcc5ebff-1d0d-4131-ac17-c2e25607e743","order_by":4,"name":"Xiao-Qiao Su","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiao-Qiao","middleName":"","lastName":"Su","suffix":""},{"id":287247620,"identity":"93cdd9ae-7999-4aa9-b89d-cd871f6343e6","order_by":5,"name":"Ming-Ying Zhang","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming-Ying","middleName":"","lastName":"Zhang","suffix":""},{"id":287247621,"identity":"81f7e0b2-9c4a-44db-bc14-8c112060f2d5","order_by":6,"name":"Le-Fei Zhu","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Le-Fei","middleName":"","lastName":"Zhu","suffix":""},{"id":287247622,"identity":"d2543a02-504a-4608-b287-75782960e9ca","order_by":7,"name":"Zhi-Ruo Lin","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Ruo","middleName":"","lastName":"Lin","suffix":""},{"id":287247623,"identity":"82cbf91c-dca7-4b4a-985d-3840de8aa84b","order_by":8,"name":"Fang Cheng","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Cheng","suffix":""},{"id":287247624,"identity":"6ad6e5a7-4965-4dd3-a6a5-1bc9de6e8698","order_by":9,"name":"Shang-Ren Xie","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shang-Ren","middleName":"","lastName":"Xie","suffix":""},{"id":287247625,"identity":"1a71ef95-1b54-4400-89ee-5a22da54b99b","order_by":10,"name":"Ji-Chan Shi","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ji-Chan","middleName":"","lastName":"Shi","suffix":""},{"id":287247626,"identity":"20681585-900e-4c03-a3c6-fd58b974a086","order_by":11,"name":"Xian-Gao Jiang","email":"","orcid":"","institution":"Dingli Clinical College Of Wenzhou Medical University, Wenzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xian-Gao","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2024-03-30 17:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4193207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4193207/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-10509-1","type":"published","date":"2025-02-05T15:57:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54320978,"identity":"7ce0fe72-d94f-439b-94fa-3acaf00d40ea","added_by":"auto","created_at":"2024-04-08 19:23:49","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36237,"visible":true,"origin":"","legend":"\u003cp\u003eProportional distribution of clinical classification in the two groups of patients\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4193207/v1/08c85f0a0a0d1fd657687f5a.jpeg"},{"id":54320979,"identity":"a5aa90c7-c4b0-4b69-a947-b686c5cc66fd","added_by":"auto","created_at":"2024-04-08 19:23:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":153049,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e. Distribution of duration (in days) till clinical symptom improvement in the observation group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb. \u003c/strong\u003eDistribution of duration (in days) till clinical symptom improvement in the control group.\u003c/p\u003e","description":"","filename":"floatimage2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4193207/v1/05228bb6b4936f6b4100ea52.jpg"},{"id":75931204,"identity":"5d1307b8-be1a-416b-88b6-40e5be5273e0","added_by":"auto","created_at":"2025-02-10 16:14:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1082366,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4193207/v1/65f00e9c-0789-4833-88b3-a0f13cadfdb9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Characteristics of COVID-19 Reinfection: A Retrospective Study in China","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCoronavirus disease 2019 (COVID-19), caused by a newly discovered coronavirus in recent years, has emerged as one of the three most severe coronavirus outbreaks, alongside the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2002 and Middle East respiratory syndrome coronavirus in 2012. Since its emergence in late 2019, COVID-19 has rapidly spread worldwide, with the cumulative number of infections exceeding hundreds of millions. With the continuous mutation of coronaviruses [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the Omicron variant has gained rapid prominence globally since November 2021 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], now establishing itself as the dominant strain in the ongoing pandemic [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Notably, the Omicron variant exhibits high transmissibility but significantly reduced pathogenicity compared to those of the original strain [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, due to the mutability of Omicron's antigenic sites, it possesses a remarkably high capacity for immune evasion, posing a higher risk of reinfection to the population [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. An analysis conducted by the UK Office for National Statistics on COVID-19 cases from July 2020 to November 2022 revealed the highest repeat infection rate of 16.6% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Since December 2022, various regions in China have gradually lifted the treatment policy of isolation for individuals infected with COVID-19. However, the ongoing spread of COVID-19 infections has had severe impact on public health. In the aftermath of the infection peak, understanding the clinical characteristics of COVID-19 reinfection becomes crucial for adopting effective prevention and treatment strategies.\u003c/p\u003e \u003cp\u003eHence, in this study, we aimed to elucidate the clinical characteristics of individuals with COVID-19 reinfection by comparing them with those who experienced the primary COVID-19 infection within the same time period.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1.Study patients\u003c/h2\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003cp\u003eA retrospective data collection was undertaken, focusing on patients diagnosed with COVID-19 infection in Wenzhou between April 1, 2023, and June 20, 2023. Through careful adherence to predefined inclusion and exclusion criteria, patients were categorized into two groups based on whether they had experienced COVID-19 reinfection. The observation group included patients who had experienced reinfection, whereas the control group consisted of individuals who had experienced primary COVID-19 infection. Informed consent was obtained from all enrolled patients, who were duly informed and who voluntarily agreed to participate in the study. This study was approved by the Ethics Committee of Wenzhou Central Hospital of Zhejiang Province (approval number:L2023-03-022) in China.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.2.Data collection\u003c/h2\u003e \u003cp\u003eDemographic characteristics was collected for the two groups of patients, including age, sex, medical history of underlying diseases, and vaccination history. Additionally, data on clinical classification; clinical symptoms (fever, myalgia, cough expectoration, dizziness, fatigue, loss or reduction of smell and taste, gastrointestinal symptoms [vomiting and diarrhea], chest tightness, shortness of breath, dry throat, sore throat, and sore eyes); laboratory tests (complete blood count and C-reactive protein [CRP] level); and recovery time, were collected.The information comes from the hospital's electronic medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.3.Selection criteria\u003c/h2\u003e \u003cp\u003e \u003cb\u003e2.3.1.Inclusion criteria\u003c/b\u003e: (1) Patients diagnosed with COVID-19 infection within the past 1 week, (2) aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years, and (3) weight\u0026thinsp;\u0026ge;\u0026thinsp;40 kg.\u003c/p\u003e \u003cp\u003e \u003cb\u003e2.3.2.Exclusion criteria\u003c/b\u003e: (1) Patients with concurrent influenza or other viral infections; (2) those with other serious organic diseases and an expected survival of \u0026lt;\u0026thinsp;1 month; (3) those with acute exacerbation of pulmonary diseases, such as asthma, bronchiectasis, and chronic obstructive pulmonary disease; (4) those who received antiviral medication within the last 1 week prior to enrollment; (5) those who is suspected or confirmed to have concurrent active systemic infection besides being infected with COVID-19; (6) those with known human immunodeficiency virus infection; (7) those who have had more than one instance of previous COVID-19 infections; and (8) pregnant or lactating women.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.4.Diagnostic criteria\u003c/h2\u003e \u003cp\u003eThe diagnosis of COVID-19 infection was established if the patients met the following two criteria [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]: exhibiting relevant clinical manifestations of COVID-19 infection and testing positive on either a COVID-19 nucleic acid test or COVID-19 antigen test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.5.Clinical typing\u003c/h2\u003e \u003cp\u003eClinical typing was determined based on the severity classification of COVID-19 according to the World Health Organization (WHO) as follows [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].(1)Non-severe COVID \u0026minus;\u0026thinsp;19: defined as the absence of any criteria for severe or critical case of COVID-19.\u003c/p\u003e \u003cp\u003e(2) Severe COVID-19: defined by any of the following criteria: 1) oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% on room air; 2) signs of pneumonia; 3) signs of severe respiratory distress (in adults, use of the accessory muscle, inability to complete full sentences, respiratory rate\u0026thinsp;\u0026gt;\u0026thinsp;30 breaths per minute; in children, very severe chest wall indrawing, grunting, central cyanosis, or presence of any other general danger signs, including inability to breastfeed or drink, lethargy, convulsions, or reduced level of consciousness).\u003c/p\u003e \u003cp\u003e(3) Critical COVID-19: defined by the criteria for acute respiratory distress syndrome, sepsis, septic shock, or other conditions that would normally require the provision of life-sustaining therapies, such as mechanical ventilation (invasive or non-invasive) or vasopressor therapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.6.Hospitalization criteria\u003c/h2\u003e \u003cp\u003eThe hospitalization criteria for this study were determined based on the clinical management guidelines for COVID-19 provided by the WHO [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and other local policies, which are outlined as follows:\u003c/p\u003e \u003cp\u003ePatients whose condition met any of the following criteria and are willing to be hospitalized are eligible for hospitalization:\u003c/p\u003e \u003c/div\u003e\n\u003cp\u003e1) Severe and critical cases.\u003c/p\u003e\n\u003cp\u003e2) Non-severe cases, but exhibiting prominent clinical symptoms, particularly chest tightness or respiratory distress, requiring oxygen therapy support.\u003c/p\u003e\n\u003cp\u003e3) Exacerbation of pre-existing underlying diseases that could not be controlled.\u003c/p\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.7.Treatment plan\u003c/h2\u003e \u003cp\u003eThe treatment plan was based on the dynamic guidelines for pharmacotherapy of COVID-19 published by the WHO titled, \u0026ldquo;A living WHO guideline on drugs for COVID-19\u0026rdquo; [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The general principles are as follows: for non-severe patients, control supportive therapy is administered. Paxlovid is strongly recommended for individuals with high-risk factors who may require hospitalization, whereas molnupiravir, remdesivir, sotrovimab, and casirivimab/imdevimab are weakly recommended. For severe and critical patients, corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase inhibitor (baricitinib) are strongly recommended.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.8.Statistical methods\u003c/h2\u003e \u003cp\u003eData were processed using IBM SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, USA). Normality test and homogeneity of variance test were performed for measurement data. Normally distributed data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), whereas non-normally distributed data were presented as median and interquartile range (M[P25, P75]). Count data were described using frequency and percentage. For measurement data that met the normality and homogeneity of variance assumptions, the independent samples t-test was used for between-group comparisons. When these assumptions were not met, a non-parametric statistical test, the Mann Whitney U test, was used. The between-group comparison of count data was conducted using the chi-square test. A \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates a statistically significant difference.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.1.General conditions of enrolled patients\u003c/h2\u003e \u003cp\u003eIn the present study, we initially collected data from a total of 1,025 patients who were diagnosed with COVID-19 infection in Wenzhou between April 1, 2023, and June 20, 2023. After applying the inclusion and exclusion criteria, 120 patients who did not meet the criteria were excluded. Consequently, 905 patients were included in the study, with 407 in the observation group and 498 in the control group. No significant differences in demographic characteristics were observed between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The comorbidity history of the patients included hypertension, diabetes, hepatitis B, tumor (stable stage), tuberculosis (stable stage), coronary heart disease (stable stage), rheumatic disease (stable stage), and others. Vaccination history encompassed any dose of COVID-19 vaccine (including adenovirus vector, inactivated, or recombinant protein vaccines) they had received. According to the Epidemic Control Center data, the prevalent regional epidemic strains of COVID-19 were the Omicron variants including, the XBB series (the most widespread), with its top three subvariants being XBB.1.9, XBB.1.16, and XBB.1.22, and their respective sub-branches. In the observation group, the time intervals between the reinfection and primary COVID-19 infection varied. Specifically, 6, 54, 304, 40, 1, 1, and 1 cases of reinfection occurred within an interval of 3, 4, 5, 6, 11, 12, and 14 months, respectively. The mean interval length was 5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.877 months, with a median of 5 months.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the demographic characteristics between the two groups of patients. (n\u0026thinsp;=\u0026thinsp;1,025)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObservation group\u003c/p\u003e \u003cp\u003e(x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et/χ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge `(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199 (48.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e242 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e208 (51.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e256 (51.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical history of underlying diseases\u003c/p\u003e \u003cp\u003e[number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157 (38.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e211 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of one disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (22.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of two diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of three or more diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of vaccination [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e340 (83.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e432 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: All \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.2.Comparison of clinical symptoms between the two groups\u003c/h2\u003e \u003cp\u003eThe differences in clinical symptoms between the two patient groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the observation group, the top three clinical symptoms of COVID-19 were fever (318, 78.1%), cough with expectoration (300, 73.4%), and dizziness with fatigue (188, 46.2%). Similarly, in the control group, the top three clinical symptoms were fever (446, 89.6%), cough with expectoration (338, 67.9%), and dizziness with fatigue (197, 39.6%). The differences in the occurrence rates of clinical symptoms between the two groups were statistically significant (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;113.537, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In this study, among the patients with fever in the observation (n\u0026thinsp;=\u0026thinsp;318) and control (n\u0026thinsp;=\u0026thinsp;446) groups, the median peak temperatures during the course of illness were 38.3\u0026deg;C (37.4\u0026deg;C\u0026ndash;40.0\u0026deg;C) and 39\u0026deg;C (37.4\u0026deg;C\u0026ndash;40.5\u0026deg;C), respectively. The difference in peak temperatures between the two groups was statistically significant (t\u0026thinsp;=\u0026thinsp;14.210, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the clinical characteristics between the two groups of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObservation group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et/χ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e113.537\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e318 (78.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e446 (89.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e161 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.919\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough with expectoration\u003c/p\u003e \u003cp\u003e[number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300 (73.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e338 (67.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness with fatigue [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e197 (39.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss or reduced sense of smell and taste [number (%)]]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.503\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal symptoms (vomiting, diarrhea)\u003c/p\u003e \u003cp\u003e[number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest tightness and shortness of breath [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e144 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44.605\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDry throat and sore throat [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e180 (36.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.580\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSore eyes [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.294\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.646\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian peak temperature (\u0026deg;C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.3 (37.4\u0026ndash;40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39.0 (37.4\u0026ndash;40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 nucleic acid cycle threshold (CT) value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN gene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.36\u0026thinsp;\u0026plusmn;\u0026thinsp;5.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.542\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eORF1a/b gene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.19\u0026thinsp;\u0026plusmn;\u0026thinsp;4.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28.10\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocyte count [\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.748\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein [mg/L]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.90\u0026thinsp;\u0026plusmn;\u0026thinsp;11.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.21\u0026thinsp;\u0026plusmn;\u0026thinsp;12.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.310\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e115.843\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-severe\u003c/p\u003e \u003cp\u003e[number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e344 (84.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e307 (61.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (15.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e185 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCritical [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization [number (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e158 (31.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37.644\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of clinical symptom improvement (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.45\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.3.Comparison of the CT values of COVID-19 nucleic acid between the two groups\u003c/h2\u003e \u003cp\u003eAmong the 905 enrolled patients, 320 and 585 were diagnosed with positive COVID-19 antigen and positive COVID-19 nucleic acid, respectively. In the observation and control groups, 244 and 341 patients had positive COVID-19 nucleic acid, respectively. The mean CT values of COVID-19 nucleic acid N gene were 28.76\u0026thinsp;\u0026plusmn;\u0026thinsp;4.93 and 27.49\u0026thinsp;\u0026plusmn;\u0026thinsp;5.61 in the observation and control groups, respectively. The difference in values for the COVID-19 nucleic acid N gene between the two groups was statistically significant (t\u0026thinsp;=\u0026thinsp;2.542, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011). For the COVID-19 nucleic acid ORF gene, the observation and control groups exhibited mean values of 29.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.82 and 28.76\u0026thinsp;\u0026plusmn;\u0026thinsp;4.93, respectively. The difference in values for the COVID-19 nucleic acid ORF gene between the two groups was statistically significant (t\u0026thinsp;=\u0026thinsp;2.480, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.4.Comparison of laboratory examination indicators between the two patient groups\u003c/h2\u003e \u003cp\u003eAmong the 905 enrolled patients, 421 (observation group, n\u0026thinsp;=\u0026thinsp;136; control group, n\u0026thinsp;=\u0026thinsp;285) underwent routine blood and/or CRP examinations. The mean leukocyte counts in the observation and control groups were 5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19 (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L) and 6.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37 (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L), respectively, demonstrating no significant difference between the two groups (t\u0026thinsp;=\u0026thinsp;0.321, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.748). Regarding CRP, the observation and control groups exhibited mean values of 10.90\u0026thinsp;\u0026plusmn;\u0026thinsp;11.45 (mg/L) and 12.21\u0026thinsp;\u0026plusmn;\u0026thinsp;12.76 (mg/L), respectively, demonstrating no significant difference between the two groups (t\u0026thinsp;=\u0026thinsp;1.016, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.310), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.5.Comparison of severity between the two patient groups\u003c/h2\u003e \u003cp\u003eUsing the WHO severity classification of COVID-19, the patients were categorized into different groups. In the observation group, out of 407 patients, 344, 63, and 0 were categorized as non-severe, severe, and critical cases. In contrast, out of 498 patients in the control group, 307, 185, and 6 were categorized as non-severe, severe, and critical cases, respectively. The differences were statistically significant between the two groups (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;115.843, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Regarding hospitalization, 58 (14.3%) and 158 (31.7%) patients required hospitalization in the observation and control groups, respectively, with statistically significant difference between the two groups (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;37.644, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e3.6.Duration till clinical symptom improvement in the two groups\u003c/h2\u003e \u003cp\u003eBased on the WHO treatment approach, patients in both the groups received appropriate treatment. The duration till clinical symptom improvement in the observation and control groups ranged from 1 to 30 (mean duration, 5.45\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70) and 1 to 40 (mean duration, 8.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55) days, respectively, demonstrating statistically significant difference between the two groups (t\u0026thinsp;=\u0026thinsp;10.209, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The distribution of the duration till clinical symptom improvement in the two groups is illustrated in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003ea and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, respectively.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOver time, the SARS-CoV-2 has continued to evolve, giving rise to new variants of concern (VOC). The VOCs (including alpha, beta, gamma, delta, and Omicron) have demonstrated the virus\u0026rsquo;s ability to adapt to the host and evade host immune responses, thereby weakening the neutralizing efficacy of antibodies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], leading to an elevated risk of reinfection with COVID-19. In late December 2022, China experienced a widespread outbreak of COVID-19, with most individuals experiencing primary infection. These individuals may now face the risk of developing reinfection with the SARS-CoV-2. The present study aimed to investigate the clinical characteristics of patients experiencing COVID-19 reinfection by comparing them with those who experienced primary infections during the same time period.\u003c/p\u003e \u003cp\u003eIn this study, patients experiencing COVID-19 reinfection developed infection at an interval of \u0026gt;\u0026thinsp;3 months since their primary infection. Over time, as the number of infections increased, the average interval became 5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.877 months, with a median of 5 months. This interval is shorter than what had been previously reported (\u0026gt;\u0026thinsp;200 days) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and may be attributed to the difference in study duration. Additionally, the changes in the circulating strains could have potentially influenced these results. A significant increase in the number of infections was observed in the fourth and fifth months after the primary infection, followed by a decrease after the 6-month interval. Liew et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] also observed that nasal antibodies against the Omicron variant persisted for only 3\u0026ndash;5 months, which could be an important factor contributing to repeated Omicron variant infections. Limited data on infections occurring beyond 6 months were identified in this study, possibly due to the relatively short timeframe since the gradual lifting of COVID-19 control policies in China, with most included patients experiencing COVID-19 reinfection in \u0026lt;\u0026thinsp;6 months of their primary infection. Therefore, further exploration is required to understand the data on COVID-19 reinfection occurring after an interval of 6 months. Furthermore, in accordance with the WHO\u0026rsquo;s definition of COVID-19 reinfection [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], all reinfection patients in this study occurred after an interval\u0026thinsp;\u0026gt;\u0026thinsp;3 months since their primary infection. This finding demonstrated that they were indeed COVID-19 reinfection rather than instances of COVID-19 viral reactivation.\u003c/p\u003e \u003cp\u003eIn this study, the observation group exhibited proportions of 84.5% non-severe, 15.5% severe, and 0% critical cases in clinical classification. These proportions significantly differed from those in the control group, which had 61.7% non-severe, 37.1% severe, and 1.2% critical cases. These findings indicated that COVID-19 reinfection patients were predominantly non-severe, with a lower proportion of severe and rare occurrence of critical cases. Moreover, when comparing the hospitalization rates between the two patient groups, a significantly lower proportion of patients experiencing reinfection required hospitalization that that of patients experiencing primary COVID-19 infections. This suggested that the severity of COVID-19 reinfection patients is generally milder than that of primary infections. However, it should be noted that this study only included patients who actively sought medical care at the hospital, and a substantial number of patients with milder symptoms might not have visited the hospital, potentially leading to an underestimation of the proportion of non-severe cases and an overestimation of that of severe and critical cases.\u003c/p\u003e \u003cp\u003eWhen comparing the clinical symptoms between the two groups, the top three clinical symptoms in both the groups (fever, cough with expectoration, and dizziness with fatigue) differed significantly, with a lower rate of fever evident in the observation group. In COVID-19 reinfection group, the primary clinical symptoms continued to be fever, cough with expectoration, dizziness with fatigue, dry throat, sore throat, and myalgia. However, the occurrence rate of fever symptoms was lower in COVID-19 reinfection group than in primary COVID-19 infection group; this contrasts with the findings of previous reports suggesting that approximately 85% of COVID-19 reinfection patients are asymptomatic [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The median highest body temperature for theCOVID-19 reinfection groups was 38.3\u0026deg;C, which was lower than that observed for the primary COVID-19 infections group (39.0\u0026deg;C), suggesting that fever symptoms are less severe in COVID-19 reinfection patients than in primary COVID-19 infection. The median duration for complete or substantial symptom improvement was 5 and 7 days for patients with reinfection and primary infections, respectively. Consequently, we inferred that patients experiencing COVID-19 reinfection recover from clinical symptoms at a faster rate than patients experiencing primary infections do. These findings align with the findings of West [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], who reported milder symptoms and faster recovery in cases of COVID-19 reinfection. In addition, the COVID-19 Forecasting Team [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] analyzed data from 65 studies across 19 different countries and reported that following a previous infection with the Omicron variant, the antibodies levels rapidly decline over time, leading to a rapid decrease in protection against reinfection with COVID-19. However, protection against severe cases continues for a relatively longer duration. This notion corresponds with the low proportion of severe and rare critical cases observed in the observation group in the present study. When comparing the CT values of the COVID-19 nucleic acid between the two groups, the observation group exhibited lower N gene and ORF gene values that those of the control group, indicating a lower viral load in patients experiencing COVID-19 reinfection than that of patients experiencing primary infections.\u003c/p\u003e \u003cp\u003eThis study had certain limitations. The different timing of patient visits and COVID-19 nucleic acid sampling after symptom onset might have affected the accuracy of the COVID-19 nucleic acid CT values in accurately reflecting the viral load at a specific moment after infection.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003ePatients experiencing COVID-19 reinfection are primarily classified as having non-severe conditions, with a low proportion of occurrence of severe and rare critical conditions. Their severity is milder than that of patients experiencing primary COVID-19 infections. Additionally, the viral load is relatively lower, and the duration till clinical symptom recovery is shorter in patients experiencing reinfection. Furthermore, a lower proportion of these patients requires hospitalization. It can be seen that the condition of COVID-19 reinfection is relatively mild, and we do not need to be overly anxious and panic in the face of the COVID-19 reinfection. At the same time, we should not completely ignore the harm caused by the COVID-19. Studies have found that with the increase of the number of the COVID-19 infections, the risk of all-cause mortality and adverse health consequences will also increase [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. We should treat the COVID-19 infection rationally, and in the face of the COVID-19 reinfection, we should not worry too much, but also do a good job of personal protection. Avoid repeated infection with the COVID-19.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOVID-19：Coronavirus disease 2019；WHO：the World Health Organization.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e7.1Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all enrolled patients, who were duly informed and who voluntarily agreed to participate in the study.\u0026nbsp;This study was approved by the Ethics Committee of Wenzhou Central Hospital of Zhejiang Province (approval number:L2023-03-022) in China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.2.\u003c/strong\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;in this section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.3.\u003c/strong\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to protect study participant privacy but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.4.\u003c/strong\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\u003e7.5.\u003c/strong\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.6.\u003c/strong\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eC.C.Q. and X.G.J . were involved in the conception and design. Q.Z., Y.L.C, X.Q.S., M.Y.Z., L.F.Z, F.C., S.R.X. and L.F.Z. collected the data. X.Q.L.were involved in the analysis and interpretation of the data. Z.R.L.,F.C and S.R.X searched, sorted, and interpreted the relevant literature. C.C.Q.and J.C.S.were involved in the drafting of the paper, revising it critically for intellectual content. All authors edited and approved the final manuscript and agree to be accountable for all aspects of the work.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGobeil S-M, Henderson R, Stalls V, et al. Structural diversity of the SARS-CoV-2 Omicron spike. Molecular Cell, 2022, 82(11):2050-2068. DOI：10.1101/2022.01.25.477784.\u003c/li\u003e\n\u003cli\u003eEl-Shabasy RM, Nayel MA, Taher MM, Abdelmonem R, Shoueir KR, Kenawy ER,et al.. Three waves changes, new variant strains, and vaccination effect against COVID-19 pandemic. Int J Biol Macromol. 2022 Apr 15;204:161-168. DOI: 10.1016/j.ijbiomac.\u003c/li\u003e\n\u003cli\u003eLiu M, Zhang B-Y, Zhao L-H,et al.Pathogenesis and epidemiology of Omicron, a new coronavirus variant[J]. China Practical Medicine,2023,07:160-163. DOI：10.14163/j.cnki.11-5547/r.2023.07.044.\u003c/li\u003e\n\u003cli\u003eLu Y J,Okpani A I,McLeod C B,et al. Masking strategy to protect healthcare workers from COVID-19:An umbrella meta-analysis.[J]. Infection, disease \u0026amp; health,2023,01:2468-0869. DOI:10.1016/J.IDH.2023.01.004.\u003c/li\u003e\n\u003cli\u003ePeng D-P,Xing X-Y,Wang Y,Zhang K-Y,Niu J Q,et al. Epidemiologic and clinical characteristics of a novel omicron variant of coronavirus[J]. Chinese Journal of Viral Diseases,2022,05:385-389. DOI：10.16505/j.2095-0136.2022.0058.\u003c/li\u003e\n\u003cli\u003eChen J, Wang R, Gilby NB, et al. Omicron variant (B.1.1.529): infectivity, vaccine breakthrough, and antibody resistance[J]. J Chem Inf Model, 2022, 62(2): 412 422. DOI: 10.1021/acs.jcim.1c01451.\u003c/li\u003e\n\u003cli\u003eSatistics OFN. Coronavirus (COVID-19) Infection Survey, characteristics of people testing positive for COVID-19, UK. 2022 [EB/OL].(2022) Available at：https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/coronaviruscovid19infectionsinthecommunityinengland.\u003c/li\u003e\n\u003cli\u003eYahav D, Yelin D, Eckerle I, Eberhardt CS, Wang J, Cao B, Kaiser L. Definitions for coronavirus disease 2019 reinfection, relapse and PCR re-positivity. Clin Microbiol Infect. 2021 Mar;27(3):315-318. doi: 10.1016/j.cmi.2020.11.028. Epub 2020 Dec 5.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. COVID-19 Clinical management: living guidance[EB/OL].(2023)Available at：https://www.who.int/teams/health-care-readiness/covid-19.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Update to living WHO guideline on drugs for covid-19.[J]. BMJ (Clinical research ed.),2023,380(57):1756-1833. DOI：10.1136/bmj.p57.\u003c/li\u003e\n\u003cli\u003eGarciaBeltran W F, Lam E C, ST DENIS K, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity[J]. Cell, 2021,184(9):2372-2383. DOI:10.1016/J.CELL.2021.04.006.\u003c/li\u003e\n\u003cli\u003ePlanas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization[J]. Nature, 2021, 596(7871)：276-280. DOI:10.1038/S41586-021-03777-9.\u003c/li\u003e\n\u003cli\u003eBastard J, Taisne B, Figoni J, Mailles A, Durand J, Fayad M, Josset L, Maisa A, van der Werf S, Parent du Ch\u0026acirc;telet I, Bernard-Stoecklin S. Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022. Euro Surveill. 2022 Mar;27(13):2200247. DOI: 10.2807/1560-7917.ES.2022.27.13.2200247.\u003c/li\u003e\n\u003cli\u003eNguyen NN, Houhamdi L, Hoang VT, Delerce J, Delorme L, Colson P, Brouqui P, Fournier PE, Raoult D, Gautret P,et al. SARS-CoV-2 reinfection and COVID-19 severity. Emerg Microbes Infect. 2022 Dec;11(1):894-901. DOI: 10.1080/22221751.2022.2052358.\u003c/li\u003e\n\u003cli\u003eLiew F, Talwar S, Cross A, Willett BJ, Scott S, et al.SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination[J].EBioMedicine,2023,87(1):2352-3964. DOI:10.1016/j.ebiom.2022.104402.\u003c/li\u003e\n\u003cli\u003eKumar V, Iyengar K, Garg R, Vaishya R,et al.. Elucidating reasons of COVID-19 re-infection and its management strategies. Diabetes Metab Syndr. 2021，15(3):1001-1006. DOI:10.1016/j.dsx.2021.05.008.\u003c/li\u003e\n\u003cli\u003eCohen C, Kleynhans J, von Gottberg A, et al. SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21. Lancet Infect Dis. 2022 Jun;22(6):821-834. doi: 10.1016/S1473-3099(22)00069-X.\u003c/li\u003e\n\u003cli\u003eBorras-Bermejo B, Pi\u0026ntilde;ana M, Andr\u0026eacute;s C, et al. Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain. Front Microbiol. 2022 May 26;13:876409. DOI: 10.3389/fmicb.2022.876409.\u003c/li\u003e\n\u003cli\u003eWest Jack. Covid-19 reinfection-what could the absence of evidence suggest[J]. The Infect Dis, 2021,53(7):486-487. DOI:10.1080/23744235.2021.1910339.\u003c/li\u003e\n\u003cli\u003eCOVID-19 Forecasting Team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis[J]. The Lancet, 2023,401(10379):833-842. DOI：10.1016/S0140-6736(22)02465-5.\u003c/li\u003e\n\u003cli\u003eBowe Benjamin,Xie Yan,AlAly Ziyad. Acute and postacute sequelae associated with SARS-CoV-2 reinfection.[J]. Nature medicine,2022,28(11)：2398-2405. DOI：10.1038/s41591-022-02051-3.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19 infection, reinfection, clinical symptoms, clinical typing, severity, Omicron variant","lastPublishedDoi":"10.21203/rs.3.rs-4193207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4193207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe number of patients with COVID-19 reinfection is gradually increasing.In this study, we aimed to investigate the clinical characteristics of individuals who experienced COVID-19 reinfection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective data analysis was conducted involving patients diagnosed with COVID-19 between April 1, 2023, and June 20, 2023. The patients were categorized into two groups: the observation group, consisting of individuals with reinfection, and the control group, comprising those with primary infection.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA Total 905(905/1025) patients were included in the study,with 407 in the observation group and 498 in the control group. The top three clinical symptoms in both groups were fever, cough with expectoration, and dizziness with fatigue (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The clinical classification of patients in the observation group primarily consisted of non-severe cases, (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). The proportion of hospitalized patients was lower in the observation group than in the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The observation group exhibited a shorter clinical symptom recovery time than that of the control group (median, 5 d vs. 7 d,\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePatients experiencing COVID-19 reinfection were primarily classified as non-severe cases, with lower proportions of occurrence of severe and rare critical conditions. The severity was milder compared to that in patients with primary COVID-19 infections.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics of COVID-19 Reinfection: A Retrospective Study in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-08 19:23:44","doi":"10.21203/rs.3.rs-4193207/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-17T05:05:10+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"8768607368336395531796636257831559083","date":"2024-12-15T06:43:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66642646956626205215033881340072027888","date":"2024-12-14T17:47:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-14T08:11:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-14T07:26:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182792564346886550475303186661445322563","date":"2024-12-14T06:27:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239647371502589300415928633127293667244","date":"2024-12-13T17:09:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176103913991638143174999157512171234873","date":"2024-12-13T14:42:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69126769582067515111646079784103174300","date":"2024-12-13T14:39:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-28T07:39:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216391020988792811315318851415700421778","date":"2024-09-23T07:42:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-23T07:26:31+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-23T04:32:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-03T03:35:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-03T01:18:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-03-30T17:50:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4f1c93de-b231-4760-a9d1-3894d46a2736","owner":[],"postedDate":"April 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:09:01+00:00","versionOfRecord":{"articleIdentity":"rs-4193207","link":"https://doi.org/10.1186/s12879-025-10509-1","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-02-05 15:57:06","publishedOnDateReadable":"February 5th, 2025"},"versionCreatedAt":"2024-04-08 19:23:44","video":"","vorDoi":"10.1186/s12879-025-10509-1","vorDoiUrl":"https://doi.org/10.1186/s12879-025-10509-1","workflowStages":[]},"version":"v1","identity":"rs-4193207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4193207","identity":"rs-4193207","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}