Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global public health threat [1,2]. This virus has the potential to cause widespread pandemic with morbidity and mortality [3]. As of 30 April, 2020, a total of 3 090 445 human COVID-19 cases had been reported to the World Health Organization, including 84 373 cases from China and 3 006 072 cases from 212 countries and regions outside of China; of these, 217 769 were fatal [2]. In view of the striking increase in COVID-19 case numbers outside of China, WHO characterizes COVID-19 as a pandemic [2], highlighting the urgent need for international efforts to halt the rapid progression of its outbreak. In order to support the control of COVID-19, all patients were admitted to hospital in China regardless of disease severity. The Chinese government also declared the implementation of the financial support for COVID-19 since January 2020 (http://www.nhsa.gov.cn/art/202 0/1/23/art_37_2284.html). The costs of medical care were primarily paid by health insurance, and the remaining costs were afforded by local government.

The spectrum of the COVID-19 severity is broad, ranging from asymptomatic to severe illness that requires mechanical ventilation [4]. In most infected people, COVID-19 is causing mild-to-moderate disease, whereas the mortality rate is markedly increased in the patients affected by severe disease [5]. Factors associated with severe presentation included elderly people and pre-existing comorbidities [6]. As a consequence, early initiation of proper therapy is essential for reducing the mortality associated with this disease. In in vitro screening studies, multiple agents were found to inhibit the SARS-CoV-2 production [7,8]; however, there is limited evidence from randomized clinical trials to support any effective drug against COVID-19. In this context, antivirals and corticosteroids used in outbreaks of other coronaviruses are the major compassionate treatment options for COVID-19 cases [9]. In addition, prophylactic antibiotics are involved in treatment of severe cases to prevent secondary infection [6,9]. The long-term administration of a dozen therapeutic drugs is associated with increased risk of adverse events, further complicating treatment regimens. For patients with critical illness, the application of unaffordable respiratory supporting devices (i.e. mechanical ventilation and extracorporeal membrane oxygenation) carries a high cost burden for patients and many funding systems [10]. Therefore, the costs of COVID-19 treatment vary drastically across individuals, depending on age, severity of disease, and comorbidity status. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process.

However, there is a paucity of studies aimed at quantifying the direct medical costs incurred by COVID-19 patients.

Shandong Province is located in eastern China, with a population of 100.7 million. As the second most populated province, it has fast economic development in the country. Despite not being close to Hubei Province, as of 3 May 2020, human-to-human transmission has driven its spread with a total of 788 confirmed cases, including 763 non-imported cases and 25 imported cases. To address this public health concern, we retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs.

An accurate understanding of cost structures is essential for clinical management of COVID-19 patients. Our data demonstrate that the overall mean cost was USD 6827 per treated episode of COVID-19, which was significantly higher than those of influenza (about USD 25), community-acquired pneumonia (about USD 650) and severe acute respiratory syndrome (about USD 2700) in China [14,15,16]. The diversity in medical expenditure majorly contributed to the aggressive treatment measure for COVID-19 cases in China. On one hand, the lack of specific drugs against this virus necessitates the use of drugs with limited evidence for COVID-19, and multiple additional drugs for prophylactic pathogen infections[17], thereby increasing the total medical cost. On the other hand, in view of high potential for acute progression [18], the more frequent monitoring of laboratory tests and radiography examinations were conducted to evaluate the clinical response for patients, which may be another explanation for the high expenditure in COVID-19 patients.

Of note, drug acquisition accounts approximately half of total direct cost in our cohort, of which immunomodulator, Chinese medicine and antibiotic occupy the top three rank positions by mean cost per case. In our opinion, this cost rank is associated with the diversity of unit price of each drug. Intravenous immune globulin therapy is the predominant immunomodulator used in the management of patients with COVID-19 [19]. Despite exhibiting satisfactory clinical benefit for clinical remission, its high cost is of concern to patients and health insurance systems in the future [20]. As the second contributor, the role of Chinese medicine in treatment of COVID-19 remains controversial [21,22]. Primary clinical experience indicated that the early intervention of Chinese medicine could impede further development of COVID-19 severity, and shorten its clinical course[22]. Further study is urgently required to determine cost-effectiveness of Chinese medicine as adjuvant therapy in the controlled randomized trials.

As expected, the patients with pre-existing diseases are strongly associated with higher cost than those without pre-existing diseases. The reasons for this observation are multifactorial. First, there is no doubt that the use of drugs for pre-existing diseases will increase the medical expense. Second, the concurrent diseases at admission imply more severity and complexity. Several studies documented that the comorbidities are recognized as independent factors in increased disease severity [23,24], thus resulting in prolonged length of hospital study and enhanced therapy measure that dramatically increase the costs of managing COVID-19 patients. In view of the extreme high cost of medical cost, early interventions are of great clinical importance for reducing the financial burden in this population.

Although the costs of medical care were paid by health insurance and local government in China, we constructed an estimated model taking the household income and health insurance scheme into consideration to assess the affordability for clinical management of COVID-19. For urban households, the proportion of insurance payment is about 70% of total in-hospital payment [25]. In this context, the urban households are less likely to incur catastrophic health expenditure at present cut-off value. By contrast, the proportion of health insurance coverage should be achieved at 80% for critically ill cases who could escape from catastrophic health expenditure for the tentative threshold. However, under the current health insurance scheme for rural household, patients have to afford approximate half of total medical cost [26]. Thus, there is an obvious gap between social requirement and current situation in health insurance. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.

There were several obvious limitations in this study. First, despite enrolment of all COVID-19 cases in our hospital, the small sample size from the single center may weaken the significance of our conclusion. Second, the present study excluded partial direct costs to patients and indirect costs, such as lost working days. Therefore, the total cost of COVID-19 patients is underestimated. Third, the insurance coverage and health benefits were significantly different across different regions in China. Hence, this study was more likely to be a theoretical cost analysis in view of that fact that Chinese government affords medical expenditures for COVID-19 patients. Fourth, despite exhibiting promising efficacy for treatment of patients infected with COVID-19, the traditional Chinese medicines are composed of several classical herbal materials for exogenous fever. Thus, it is difficult to elucidate the systemic pharmacological mechanisms of action of Chinese medicine against SARS-CoV-2. Finally, drug prices can be expected to change substantially across regions. This diversity may lead to potential bias in estimation of national financial burden. Nevertheless, our study firstly provides important insights in direct medical cost of COVID-19 patients in China.

Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the direct medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Despite government financial support to clinical management of COVID-19 patients, an estimated model indicates that improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.