Currently, the phase 3 trial concerning the efficacy of two Chinese inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults has been released on May 26, 2021, and found that 72.8% (95% CI, 58.1%-82.4%) of vaccinees in WIV04 vaccine group and 78.1% (95% CI, 64.8%-86.3%) of vaccinees in HB02 vaccine group acquired immunity against COVID-19 during a median (range) follow-up duration of 77 (1-121) days [17]. Notably, 26 vaccinees were identified as symptomatic COVID-19 after WIV04 vaccine injections, 21 vaccinees were identified as symptomatic COVID-19 after HB02 vaccine injections, the corresponding incidence rate (per 1000 person-years) was 12.1 (95% CI, 8.3–17.8) in the WIV04 group, and 9.8 (95% CI, 6.4–15.0) in the HB02 group. Additionally, a total of 26 asymptomatic cases of COVID-19 were diagnosed 14 days following the second dose (16 in the WIV04 group, 10 in the HB02 group) [17]. However, no study reported detailed information of clinical manifestations and prognosis of patients after Chinese inactivated vaccination. To the best of our knowledge, the current study is the first observational cohort to investigate Chinese imported COVID-19 patients after injection of Chinese inactivated vaccines abroad. Our results showed that the vaccine protection could last at least 8–9 months. The vaccinated patients infected with SARS-CoV-2 experienced slighter clinical manifestations when historically compared with previous local COVID-19 cases in early 2020 [19, 20]. Furthermore, our results were different with the previous study included non-vaccinated patients that showed imported cases were more severe than local cases [21].
In the current study, more than two-thirds of patients were asymptomatic infection, and for symptomatic infections, all of their symptoms were mild, no patient presented fever more than 38.0℃, shortness of breath or required high-flow nasal cannula, despite four patients received low-flow nasal cannula due to slightly reduced oxygenation. All symptomatic infections were diagnosed as mild or moderate COVID-19, and no cases were severe, required ICU care or death. Furthermore, the SARS-CoV-2 shedding period was short, and 76% of patients with negative SARS-CoV-2 on the seventh day of hospitalization. The chest CT abnormalities of symptomatic infection patients were also mild, 7 (46.7%) of them only unilateral lung involvement or no abnormalities. Although one patient was given glucocorticoid treatment for chest CT imaging progress with decreased blood oxygenation after hospitalization, the median time of imaging recovery was only 7 days.
Vaccinations have shown to be highly effective in preventing SARS-CoV-2 infections, COVID-19-related hospitalizations, severe diseases, and death [10, 15]. The latest evidence indicated that no severe COVID-19 cases were identified after receiving the Chinese inactivated vaccines, which means an efficacy of 100% against severe COVID-19 [17]. Previous studies showed that chronic comorbidity and high BMI were the risk factors of severe COVID-19, requiring ICU care or death [20, 22]. In the current study, no severe COVID-19 cases were identified. Furthermore, the chronic comorbidity and high BMI did not present any risk to contribute the individuals to develop to symptomatic infection other than asymptomatic infection. Additionally, the SARS-CoV-2 shedding period was not different in patients with or without chronic comorbidity or high BMI. These results suggest that even people with a high risk of exacerbation before SARS-CoV-2 infection, such as chronic comorbidity or high BMI, may benefit more from vaccination. Since vaccines, especially inactivated vaccines, are safe and well-tolerated, priority should be given to these high-risk population.
Immunization after infection can obtain the same protection as vaccination, with up to 90% protection against reinfection [7, 9, 10, 23]. The risk of SARS-CoV-2 infection after vaccination always have an overall higher probability of exposure to SARS-CoV-2, such as health care workers or individuals who closely contact with COVID-19 patients [9, 12]. All the patients in our study closely contacted with COVID-19 cases, suggesting that social distance and masks are still needed to prevent infection even after vaccination. More than two-thirds of the patients were asymptomatic infection, so it further emphasized the need for consecutive testing of the population who were fully vaccinated and exposed to confirmed COVID-19 patients. Furthermore, strengthening the management of these asymptomatic infections is also an important measure to prevent the spread of SARS-CoV-2 and then control the COVID-19 pandemic.
The durability of the vaccine-induced immunity protection against infection remains unknown because too little time has elapsed since the start of the vaccination campaign. Studies showed that robust neutralizing antibodies against SARS-CoV-2 re-infection in previous COVID-19 patients could maintain up to 6–12 months [23–26]. In the current study, the median interval between vaccination and infection was 88 days, and more than 210 days in 6 patients, including 4 partly vaccinated patients, a fully vaccinated individual who received inactivated vaccine may obtain longer-term immune protection. These results were similar or better than the previous reports that showed a protective effect of the vaccine might persist after 6 months of full vaccination [10, 14]. The decrease of neutralizing antibody titer may be one of the reasons for infection after vaccination; further dynamic monitoring studies are needed.
The current study has several limitations. First, only 46 cases were retrospectively included in this single center hampered us to observe potential severe COVID-19 cases among vaccinee. However, according to the latest Chinese inactivated vaccine study abroad, no severe case was identified among 25440 participants who injected the Chinese inactivated vaccines; therefore, it is normal that we did not observe any severe case in the current study. Second, these early vaccinees were all Chinese Han adults aged 18–59 years; our case series do not include the patients aged more than 60 or less than 18. Future studies need to assess the risk of post-vaccination SARS-CoV-2 infection and the disease severity in various populations, including older people and children, as well as ethnic and geographical diversity. Third, potential sources of bias may exist in this study since these imported cases from 8 countries distributed in Asia, Africa and Europe. However, they were all Chinese Han population and used inactivated vaccine may largest extent offset this deviation. Fourth, concerns have emerged regarding the breakthrough infections implies that the virus broke through a protective barrier provided by the vaccine [16, 27]. We had not performed the examination of the SARS-CoV-2 sequences and neutralizing antibody titers, thus we cannot clarify the infection due to suboptimal immune responses to the vaccines or breakthrough infections with SARS-CoV-2 variants, especially 59% patients from West Asia and South Asia where the mutant virus strain is high prevalence. Despite these limitations, our findings are important in understanding and filling the gap of the clinical characteristics in a significant number of Chinese COVID-19 patients who received Chinese inactivated vaccines abroad because there only 73 asymptomatic and symptomatic cases among 25440 participants who injected the Chinese inactivated vaccines according to the latest study [17].
In conclusion, our study indicated a potential risk of SARS-CoV-2 infections even after successful vaccination with Chinese inactivated vaccines. However, most patients present no clinical symptoms or clinically mild symptomatic COVID-19, and a shorter SARS-CoV-2 shedding period when compared to the patients in early 2020 in our previous study [20]. These observations in no way undermine the importance of the urgent efforts to vaccinate the population. Instead, it emphasizes the importance of vaccines in reducing the severity of the disease, and meanwhile, supports maintaining social distance and wearing masks to reduce the risk of reinfection even after vaccination in current circumstances.