COVID-19 has evolved into a pandemic worldwide. It led to around 0.56 million deaths with case fatality rate of 4.4% . Unfortunately, there is a lack of standardized and convincing general solutions to stop the pandemic or for clinicians to reduce the deaths in clinical practice. It may be helpful to find some effective solutions by careful retrospection of solved epidemics with a low case fatality rate and no local secondary infection cases. Compared with Hebei province, China, Zhuhai is a low epidemic area. The local epidemic began in early January and disappeared with a final case fatality rate of 1.0% and no local secondary infection cases at the end of March, 2020. Therefore, this local epidemic was suitable for the analysis of benign clinical and epidemiological outcomes-associated factors. By retrospection of this resolved epidemic episode, we found that younger age, lack of aging-related diseases, admission of all patients before the occurrences of obvious dyspnea, substantial changes of vital organs, and secondary bacterial infections and early antiviral treatment were the major benign clinical and epidemiological outcomes-associated factors. Among these associated factors, early hospitalization seemed to be the most important one. It provided chances to conduct early antiviral treatment, antibacterial and antifungal treatments in times, reasonable care and anxiety treatment. Therefore the above findings might be of many implications in combating COVID-19.
The clinical outcomes-associated factors of COVID-19 based on death cases have been broadly studied [8–12]. The fatal outcomes are correlated with the age of more than 65 years, pre-existing underlying diseases, the presence of secondary infections and the rises in blood inflammatory indicators. The disease severity is correlated with underling diseases such as diabetes, renal disease, and chronic pulmonary disease and abnormality of higher white blood cell counts, lower lymphocyte counts, and increased C-reactive protein [13–15]. Based on a solved epidemic in this study, we also found that the age and underlying comorbidities were the major factors associated with the disease severity. The younger the mean age of the patients, the lower the chance of severe illnesses was. Moreover, the underlying comorbidities were mainly aging-related diseases such as hypertension and diabetes. Thus, age seemed to be the key disease severity-associated factor. The mean age in our dataset was 46.3 years, which is much younger than that reported from China (47–55 years), Italy (65 years), Germany (65 years) and United States of America (65.5 years) [18–21]. By careful retrospection of the reports from a high epidemic area in china, the mean age was 42 years between January 16 and January 29, 2020 and 50–55 years between January 20 and February 14, 2020 [22,23], suggesting that the shift to the elders is the important contributing factor for the high case fatality in high epidemic area in China. Therefore, it is ascertained that younger age is the benign clinical outcome-associated factor of the epidemic episode in Zhuhai, China. The prevention of the elders from COVID-19 and the providing a priority to reasonable medication and care for elder patients may sharply reduce the deaths in high epidemic areas.
The commonest laboratory change is lymphopenia [6,24,25], which is similar to other viral infections [26,27]. Indeed, compared with mild/common ones, the serious/critical patients had significantly lower lymphocyte counts in this study. The lymphocyte counts in serious/critical cases began to be significantly lower 3 days before their identification dates. The absence of lymphopenia before the eighth day from disease onset can exclude the possibility of 78.5% to be serious/critical ill. These findings are helpful to reduce the pressure of the medical system by sorting patients reasonably in high epidemic areas. Except for clinical types-sorting dyspnea, those serious/critical patients on admission are more likely to have abnormalities in other vital organ functions, coagulation and secondary bacterial infections [11,28–30]. These abnormalities indeed frequently occurred in this study. However, compared with reports from high epidemic and high case fatality areas [6,22,31], the overall symptoms (fever and cough) and laboratory changes of our patients were mild on admission, especially in the lung functions. The average time of our dataset from disease onset to admission was 4.4 days, and to diagnosis was 7.8 days, implying that most serious/critical patients were diagnosed after admission. Indeed, there were only 2 patients including the dead case had dyspnea on admission. In contrast, the average time for admission was 7.0 days in high epidemic and high case fatality rate area . Therefore, laboratory data told us that early admission of all patients was the important benign clinical outcome-associated factor in this study. Patients in hospital may obtain benefits from early or in time treatments, reasonable care and anxiety remission.
The treatments of COVID-19 mainly consist of maximal supportive care and antiviral agents. Though antivirals are worldwide expected, there are no approved antiviral agents up to now. However, some drugs including chloroquine, arbidol, remdesivir and lopinavir/ritonavir have shown aspiring effects on reduction of deaths [32–36]. In this study, most patients (88.8%) completed antiviral regimen without obvious side effects, and the early antiviral treatment started within 3 days from disease onset significantly shortened the time of viral RNA-negative conversion, which was in concordance with early antiviral treatment contributing to alleviate the severity and improve the prognosis of patients , and no benefit was observed with lopinavir/ritonavir treatment beyond standard care in serious/critical patients . The average delayed time of antiviral treatment in critical cases was significantly longer than that of serious cases, suggesting that early antiviral treatment might play a role in preventing from the serious-to-critical progression, perhaps were correlated with the low case fatality rate (1.0%) in spite of the higher serious/critical rate (19.4%) in our dataset. Regretfully, antibiotics and corticosteroids were not found to be benign clinical outcome-associated factors. However, secondary bacterial infections and inflammatory factor storms play important roles in respiratory failure [32,37]. Some physicians believe that a portion of patients die of fulminant myocarditis [38,39]. Therefore, most serious/critical patients received the treatments of antibiotics and corticosteroids might be contributable to the benign clinical outcomes in this epidemic episode.
Since massive migration is considered to promote the early spread of COVID-19 in China and China's practices with isolation of patients and quarantine of persons with close contacts [41,42], the early admissions of all patients and widespread antiviral therapy might be contributable for the benign epidemiological outcome of this local epidemic episode. Early admissions might be helpful for the prevention of community infection. Early and widespread antiviral therapy might be one of the reasons of no heath worker infection since early antiviral therapy shortened the time of viral RNA-negative conversion. Nonetheless, to control this pandemic of COVID-19, there are many uncertainties . Frankly, some of associated factors concluded by rough comparison with published literature need to be confirmed in the future. We here reported them only as new clues for combating COVID-19. In addition, it is uncertain whether our successful experience is effective in high epidemic areas since the major death-contributable factor there is the lack of enough facilities to meet the needs of so many patients. However, the continuous monitoring of lymphocytes may be useful reduce the pressure of the medical system by sorting patients reasonably in high epidemic areas. We also strongly suggest that the conducts of early isolation and general antiviral therapy to mild or young patients who are suite for most current potential antivirals by any means are imperative to reduce the deaths by preventing old or fragile persons from infection in high epidemic areas.