Wuhan has borne the brunt during the epidemic. To put patients into hospital and under treatment timely, the clinically diagnosed cases had been identified from February 8 to February 18. Besides, the number of clinically diagnosed cases was revised on February 24 . After performing the clinical diagnosis, it's encouraging that the number of new cases had been trending downward, Rt had decreased to below 1, indicating the explosive growth of new infections was effectively contained in Wuhan.
This study showed that people of all ages were susceptible to the virus, but the vast majority of patients were middle-aged and old people. The median age of confirmed cases was marginally above that of clinically diagnosed cases (56 vs 54 years), and the elderly accounts for a higher proportion in confirmed cases (41.0% vs 36.6%). The occupational distributions of confirmed cases and clinically diagnosed cases were similar, but the sex ratios of them were slightly different (1.01 vs 0.86). The epidemic peak of clinical diagnosis cases was later than that of confirmed cases, which may be because that the patients with early-onset received the nucleic acid diagnosis preferentially, while the patients with late-onset couldn’t receive RT-PCR or genome sequencing of SARS-COV-2 virus in time when the detection kits were insufficient. At this time, it is necessary to carry out a clinical diagnosis for these patients who have already developed symptoms but can’t be confirmed by the laboratory, since the condition will worsen if they cannot be isolated or admitted promptly. The median (IQR) interval between onset and diagnosis of confirmed cases was 9(5–13) days, which were slightly shorter than that of clinically diagnosed cases [11(5–17) days]. Reagents were insufficient in the early stage of the outbreak, which caused them to take too long from onset to diagnosis. The interval between onset and diagnosis had seen a continuous decrease as time went by, meaning the implementation of clinical diagnosis effectively shortened the duration before diagnosis in the early stage of the outbreak.
There are 13 districts in Wuhan: Jiang'an, Jianghan, Qiaokou, Hanyang, Wuchang, Qingshan, Hongshan, Dongxihu, Hannan, Caidian, Jiangxia, Huangpi and Xinzhou, the first seven of which are city centres. The city centres have a large number of permanent residents and floating population, which is prone to the spread of the virus. Besides, the city centres have abundant and concentrated medical resources, for example, there are more tertiary hospitals (Supplementary Fig. S7), which make it easier for the infected people there to be diagnosed than suburbanites. The geographical distribution further indicated the obvious regional diversity of confirmed cases and clinically diagnosed cases. Jianghan district virtually had the highest density of confirmed cases. The Huanan Seafood Wholesale Market, which is regarded as the epidemic focus of this virus, is located here. At the end of December 2019, the National Health Commission of China reported a cluster of patients with pneumonia in Wuhan, part of which was exposure to Huanan Seafood Wholesale Market illegally selling wildlife . Jiang'an district, Qiaokou district and Hanyang district, which were all hardest-hit regions, were geographically close to Jianghan district. Hannan district had the highest density of clinically diagnosed cases, followed by Jianghan district. Hannan district is located in the suburb of Wuhan, where medical resources are relatively scarce. Although it was difficult to confirm COVID-19 promptly in the early stage of the outbreak, many patients in Hannan district had benefited from clinical diagnosis and received timely treatment. Besides, the high density of clinically diagnosed cases in Hannan district may owe to its least permanent resident population.
The proportion of severe and critical types in confirmed cases was different from that in clinically diagnosed cases (21.5% vs 14.0%, P < 0.05), one of the reasons may be that the proportions of the elderly and males were higher in confirmed cases. Logistic-regression result suggested that age was closely related to the proportion of severe and critical cases, which was consistent with early reports [9, 11, 14]. Because older people tend to have serious underlying illnesses, the older the age is, the more severe the disease is. The later the date of onset, the milder the disease state. In addition to the improved treatment effect, it may also be related to the shorter intervals between onset and diagnosis in the later stage of the outbreak. The median intervals between onset and diagnosis of severe and critical patients were significantly longer than those of mild patients. Some severe patients with critical illness who progressed to acute respiratory distress syndrome (ARDS) after mild symptoms for 7–8 days had been observed , implying the early recognition of infected cases is extremely important and mild patients should also receive early treatment to avoid becoming critically ill . Our data showed that the proportion of severe and critical cases has a continuous decrease as time went by, meaning the growth of severe and critical cases was in check in Wuhan. It should be noted that clinically diagnosed cases lived in suburbs had more critical disease compared with those lived in city centres. We speculated that was because health resources were relatively deficient in suburbs. For example, Dongxihu district, one of suburbs in Wuhan, had the highest incidence density of severe and critical clinically diagnosed cases. In regions with insufficient medical resources, clinical diagnosis is an important supplement to conventional diagnostic methods.
The case fatality rate of confirmed cases was considerably higher than that of clinically diagnosed patients (5.2% vs 1.5%, P < 0.05), of which the result consistent with the above severe rate. There has been no available wonder drug for COVID-19, so the fatality rate of severe patients is still remarkable. The outcomes of COVID-19 cases in our study were followed up to February 24, but the true ratio may not be known until the epidemic is over . According to the National Health Commission of China, a total of 50333 cases were confirmed with COVID-19 in Wuhan and 3869 died as of 30 April 2020, the case fatality rate was 7.7%. It speculates that many patients died later. Approximately 9.4% of elderly patients with COVID-19 were dying in confirmed cases group. The elderly should be regarded as the key population for epidemic prevention and control. The immune function and organ reserve capacity of the elderly are receded, and most of the elderly suffer from serious coexisting illnesses . Infectious diseases, especially acute infection will bring adverse prognosis and death risk to the elderly. The case fatality rate of males was higher than that of females, the same sex-based difference was observed in severe acute respiratory syndrome coronavirus (SARS) infection, it may be because X chromosome and estrogen protect females from lethal infection [19, 20] ; besides, numerous evidences indicted ACE2, which used by SARS-CoV-2 to enter into the host cells [21, 22], generally has a higher expression in males than in females; moreover, females and males vary in their susceptibility and response to viral infections, the number and activity of innate immune cells, and immune responses are higher in females than in males .
The transmission dynamics of COVID-19 are similar in confirmed and clinically diagnosed cases. Rt declined rapidly from the peak of 3.64 (and 3.54) for confirmed (and clinically diagnosed) cases after the lockdown of Wuhan city, and further decreased to below 1 after clinical diagnosis. It proves that rapid public health responses including the Wuhan lockdown and the implementation of clinical diagnosis, have successfully contained the spread of SARS-CoV-2 and mitigated the development of the epidemic.
Our study has several limitations. Firstly, there were a few missing values that might slightly affect the result. Secondly, patient’s outcomes were followed up to February 24, when many patients had not been discharged, so the ultimate case fatality rate couldn’t be calculated. Thirdly, data reliability of the interval between onset and diagnosis depended on the patients, which might have caused some recall bias. Finally, we once again reiterated that the results were based on the data of Wuhan which was the worst-hit region in China, so it should be prudent to extrapolate those data to areas with less epidemic.
In summary, the epidemic in Wuhan had been declining which should primarily be attributed to the swift and rigorous measures China took, especially the implementation of clinical diagnosis. The demographics of confirmed and clinically diagnosed cases were similar, and the geographical distributions of severity and fatality were complementary. In cases where medical resources are insufficient to cover the viral nucleic acid test of all COVID-19 cases, clinical diagnosis is effective and necessary. Clinical diagnosis is helpful to shorten the interval between onset and diagnosis, quarantine or treat patients as soon as possible, and improve the cure rate. To decrease the case fatality rate of COVID-19, it is necessary to carry out key monitoring, prevention and control of the elderly men, and strengthen early warning and intervention of severe and critical cases.