Coronaviruses are known through SARS-CoV and MERS-CoV; and both are zoonotic diseases. Like the previous two coronavirus outbreaks, fever and cough were the most common symptoms with viral pneumonia. Our study showed that patients with severe COVID-19 had higher febrile temperatures and there was a large number of fevers in the overall population. For those previously healthy young adults with sound immunity, the occurrence of high fever after viral infection indicated that the body's rapid reaction against invaded pathogen. It revealed that fierce inflammatory reaction in patients was one of the factors leading to severe status. Anorexia also showed outstanding significant in our study, we presumed it acted as a co-occurrenced symptom with fever. Considering that patients with high fever accompanied with anorexia, it could have stronger discriminative nature than fever (P = 0.001). Previous study showed that dyspnea and chest tightness were indicators toward severe COVID-19. Inversely, we found that both symptoms were meaningless to distinguish severe COVID-19 in previously healthy young adults. Infact, there were only 7 patients (2 in severe group and 5 in mild group) had dyspnea and 39 patients had chest tightness (11 in severe group and 28 in mild group) in the admission. Due to the relatively good state of the lungs, we infered that there was less probability of respiratory decompensation at admission. Besides, a great sample size was needed for a more powerful provement. Moreover, In those patients, we found that patients with older ages need beware of aggravation of the disease. Because an older age indicated the decline of organ function and the ability of body self-regulation.
Our study showed that the estimated rate of COVID-19 severity in patients was 22.76%, which was lower than that of the previous study. This is possibly attributed to the single-center design of this study, and we collected the previously healthy young part of patients, causing possible bias in patient distribution. Moreover, based on the results of our study, sex difference was not associated with the development of severe COVID-19, a result consistent with the previous study.
It is believed that previously healthy young adults usually have sound immune system; thus, they can immediately and accurately respond to invading pathogens and viruses. However, the reasons they quickly develop respiratory failure or acute respiratory distress syndrome (ARDS) after being infected with SARS-Co-2 are still unclear. We presume that the first reason is possibly attributed to the pathophysiology of the viral load. Tiny viral loads allow the immune system to produce antibodies whether any clinical symptoms are not experienced by the body or not. However, when a significant number of viruses invade the body in a short period of time, the immune system will be overwhelmed, resulting in massive cytokine reaction that ultimately damages the lung’s tiny vessels. It will subsequently result in pulmonary edema, providing significant burden to the circulatory system, eventually crushing the heart and lungs as well as causing coagulation and massive tiny thromboses in the tiny vessels of the whole body. Recently, Zou et al. have proven the presence of viral load of upper respiratory tract that was detected in the asymptomatic patient was similar to that in the symptomatic patients. According to another previous study, the lower respiratory tract specimens usually have significantly higher viral loads and genome fractions than the upper respiratory tract specimens. The second reason is possibly attributed to the different inflammatory responses of each individual, which also play a crucial role in coronavirus-induced lung injury and ARDS. CRP is a nonspecific marker of inflammation which was widely used as biochemical indicator for reflecting the acute severe systemic inflammatory response caused by viral infection, such as our research illustrated that the severe COVID-19 patients had a high value than mild ones. In 2003, corticosteroid was widely administered in the treatment of SARS to control pulmonary inflammatory edema by regulating the immunity responses toward SARS-CoV. Russell et al announced that corticosteroids should be administered before inflammatory storm occurs to prevent lung injury. However, recently, most studies have reported that corticosteroids could only delay viral clearance and are insignificantly associated with mortality rate in severe viral pneumonia. Moreover, recently, according to Wang et al.’s study comprising 46 COVID-19 patients, low-dose and short-term administration of corticosteroids was associated with a faster improvement of clinical symptoms and absorption of lung focus. However, patients may significantly benefit whrn the medication is administered at the right time with a reasonable dose.
Elevated D-dimer levels in COVID-19 are associated with poor clinical outcomes has been proven. Tiny thromboses are produced by inflammatory cascade, blocking the pulmonary vessel, which might possibly result in disseminated intravascular coagulation (DIC) without stopping inflammation. In fact, in clinical practice, low-molecular-weight heparin (LMWH) is administered to prevent thrombosis if the D-dimer levels are > 4ug/ml. Inflammatory reaction includes cytokine storm, resulting in internal environmental disruption, inducing coagulation maladjustment. Patients in the intensive care unit (ICU) or who died may present a final phase of body decompensation, with elevated D-dimer. The study we conducted could be an early phase before coagulation decompensation. The increase in Fib levels and decrease in PLT counts could be a coagulation compensation before D-dimer elevating.
Lymphopenia is commonly assessed in most viral infections, specifically type A and B influenza. According to previous study, lymphopenia was also observed in SARS and MERS. Coronavirus infection usually induces immune response, resulting in decreased CD4 count and immunosuppression[22, 23]. Simultaneously, virus also damages the epithelial walls, and the disruption of surfactant in the airways, providing access to rapid bacterial growth, and resulting in a secondary bacterial infection, adversely affecting immunosuppressed patients.
Our study also has limitations. Firstly, considering that this was a single-center, retrospective study with limited sample size, avoiding bias regarding patient distribution is considered difficult. Secondly, lymphopenia was observed do contribution to outcomes in this study, but data regarding CD4 and CD8 counts and other inflammatory biomarkers were not assessed; these biomarkers may also possibly associate with the patients’ clinical outcomes.
In summary, this is the first study to systematically describe the clinical symptoms and laboratory biomarkers of COVID-19 in mild and severe groups of previously healthy young adults. For these patients who were admitted to hospital, if they had higher fever body temperature and symptoms of anorexia, biochemical examination showed higher CRP, and lymphopenia. Then the patient is more likely to progress to severe COVID-19. Further more, lymphopenia was considered as the strongest predictor of poor clinical outcomes. Our study findings are possibly beneficial for physicians to comprehensively understand the predictive factors associated with disease severity for COVID-19, allowing them to immediately and accurately provide supportive treatment, preventing the rapid development of the disease and decreasing the mortality rate. However, additional multicenter, prospective studies are required to further assess the clinical outcomes of severe COVID-19.