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.