The emergence in 2013 of novel avian influenza A H7N9 virus posed a pandemic threat to humans at the time, when human cases of infection from the virus occurred during annual winter–spring epidemics in mainland China (1). Fortunately, in September 2017, the successful development of an H5/H7 bivalent inactivated vaccine for chickens eliminated human infection with H7N9 virus (2, 3), and only three H7N9 cases have been reported since 1 October 2017 (2). Nevertheless, between 2013 and 30 September 2017, 1398 H7N9 cases and 560 H7N9 fatal cases were reported through the national surveillance system for notifiable infectious diseases in mainland China.

In December 2019, a novel coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan, China (4). Subsequently, outbreaks of human infections with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) occurred in 220 countries around the world (5). On 31 January 2020, the World Health Organization declared the COVID-19 outbreak to be a public health emergency of international concern (6). As of 13 September 2021, more than 21 million cases of COVID-19 had been reported globally, including 4,443,898 fatal cases around the world (7).

Here, we summarize the survival time and causes of clinical course changes in fatal cases of COVID-19 in mainland China compared with confirmed cases of H7N9 virus infections in the same region.

Human infection with H7N9 virus and SARS-CoV-2 were two respiratory infectious disease pandemics in China in recent decades that posed a major threat to public health, since these viruses may acquire mutations that enable efficient and sustained human-to-human transmission and lead to pandemic. Therefore, in this study, we compared the clinical processes of the two infectious diseases and confirmed their significantly different survival times by KM and RMST models. We found that male, having underling medical condition, older age were high-risk groups of COVOD-19 and H7N9 infection. Antibiotics, oxygen treatment, and corticosteroids were protective factors for fatal COVID-19 cases. In contrast, antiviral drugs and corticosteroids were the protective factors for H7N9 fatal cases.

We found that both COVID-19 and H7N9 fatal cases were mostly male, older, and with at least one underlying condition. Vaccine is the most effective method for preventing infectious disease, especially among high-risk populations. The H5/H7 bivalent inactivated vaccine for chickens was first used in September 2017, and the H7N9 virus isolation rate in poultry dropped by 93.3% following vaccination (4). Since most H7N9 cases had avian transmission, and human to human infection was limited, the avian vaccine was also effective in blocking human infections with H7N9 virus, and only three further cases of infection have been reported since September 2019. However, the current pandemic's SARS-CoV-2 pathogen spreads more widely and quickly and is highly transmissible from human to human (10), which leads to it posing a pandemic threat to human beings (11) and having a greater impact on the world. Therefore, effective vaccination of humans is particularly important as a means to prevent and block transmission. In China, as of 26 August 2021, more than two billion doses of COVID-19 vaccine had been distributed, and nearly 890 million people had completed the vaccination program. In the latest round of epidemics, the vaccination of COVID-19 has played a definite role in controlling it.

Early detection, diagnosis, and treatment form the basis for controlling and eliminating infectious diseases and improving survival opportunity. For H7N9 cases, early detection can control the disease process as much as possible and reduce the proportion of severity and death. However, for COVID-19 cases, early detection and diagnosis are not only to reduce severity and death but also to reduce the transmission of the SARS-CoV-2 virus. In the early stages of the COVID-19 epidemic, this new and emerging infectious disease was not fully understood, chaos, and resource limitations, so the time interval from illness onset to death was shorter, and that from illness onset to diagnosis was longer. However, greater understanding of COVID-19 and the continuous refinement and improvement of diagnostic criteria and improved sensitivity of detection kits not only accelerated the diagnosis of COVID-19 cases but also facilitated timely and accurate prevention and control. Nevertheless, false-negative test results may occur in up to 20–67% of cases (12); therefore, highly clinically suspicious patients should not rely solely on the results of RT-PCR tests, and clinical and epidemiological investigation should be carefully considered (13). In addition, the sensitivity of testing varies with the timing of testing relative to exposure (12). It is estimated that such sensitivity is 62% on the day of symptom onset and 80% on the third day after that, but it falls to only 33% 4 days after exposure (12, 14, 15). Therefore, timely sampling for detection is an important method for reducing false negative tests. Moreover, high-risk groups need to increase the number of their RT-PCR tests and to appropriately extend their isolation period.

At present, although there is no evidence to show that specific drug treatments are effective against suspected or confirmed cases with COVID-19 or H7N9, antiviral therapy and organ support therapy are the cornerstone of the treatment of severe cases with both diseases (16, 17). Our study indicated that more than half of the fatal COVID-19 and H7N9 cases received antibiotics (93.79 and 100.00%), antiviral drugs (55.52 and 82.86%), corticosteroids (64.48 and 55.74%), and oxygen treatment (88.97 and 97.75%) after hospital admission. Our study found that, without specific drug treatment for COVID-19 and H7N9, corticosteroid was a protective factor. This has been proven in research at Oxford University, where the latest study showed the ability of dexamethasone to reduce the risk of death by 54% in cases with COVID-19 requiring ventilation (18). In addition, recent research has indicated that the appropriate use of corticosteroids together with other remedies should be beneficial for severe cases of COVID-19 and H7N9 to prevent ARDS development (19, 20). Separately, severe COVID-19 cases are susceptible to secondary bacterial infection; therefore, a combination of antibiotics can also prolong the survival time of fatal cases and decrease the risk of death of COVID-19 cases requiring oxygen inhalation by 20% (18). For H7N9 cases, early initiation of antiviral therapy in patients is an important method to delay severity and death (17).

Surveillance is the most effective early warning method for emerging infectious diseases, and effective public health emergency management can reduce the adverse impact of emerging infectious diseases (21). In response to the 2003 severe acute respiratory syndrome outbreak, China established the National Notifiable Infectious Disease Surveillance System (NNIDSS) for 39 infectious diseases (22). The establishment of NNIDSS strengthened the construction of China's system for infectious diseases and public health emergencies (23) and played an important role in the outbreak of H7N9 avian influenza and the COVID-19 epidemic (21). However, infectious diseases have emerged one after another in recent years, and the existing surveillance system does not seem to be sufficient for the early warning of emerging infectious diseases. The Chinese government needs to consider further how to improve the existing surveillance system and its early warning role.

This study has some limitations. First, we only collected data on fatal cases, and mild and moderate cases were not included in the study; thus, a comprehensive comparison of survived and deceased cases was not possible. Second, we only collected information on early fatal COVID-19 cases, limiting our ability to characterize the differences between different variants. Third, some potential factors associated with survival time were not collected, which may cause bias. However, the most important factors have been collected.

In conclusion, we have described the clinical characteristics of fatal cases with COVID-19 and H7N9. We found the proportion of males, those having one or more underlying medical condition, and older age were high in these fatal cases. Moreover, from the perspective of individual treatment, offering antibiotics, oxygen treatment, and corticosteroids to COVID-19 cases extended the survival time. However, antiviral therapy and corticosteroids were more effective in H7N9 cases. Last, continued global surveillance of COVID-19 and human infections with avian influenza A viruses remains an essential component of pandemic preparedness.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Review Committee of the Jinyin-tan hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

SL and HJ conceived, designed, and supervised the study. CH, LS, ST, LK, WL, NZ, and DZ collected and cleaned the data. FL, HJ, RH, and JY analyzed the data. HJ and FL wrote the drafts of the manuscript. SL, HJ, WL, and T-CC interpreted the findings. SL and CH commented on and revised the drafts of the manuscript. All authors have read and approved the final manuscript.

This work was supported by Zhejiang Scientific and Technological Major Project under the 2020 Emergency Grant (Grant Number 2020C03124) entitled Key Technologies for Prevention and Control of Pneumonia Caused by Novel Coronavirus Infection, the Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control (Grant Number 2020XGZX047), and the Fundamental Research Funds for the Central Public-Interest Scientific Institution (Grant Number 2022-PT320-01).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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