Previously published studies have showed that severe COVID-19 patients were much older than non-severe patients and associated with higher frequency of comorbidities [6, 7, 10], and those older patients often died of their pre-existing comorbidities. However, none patient in our study had underlying comorbidities, and they all rapidly progressed to severe pneumonia and multiple organ failure with the age younger than 60 years. Thus, it is necessary to investigate the clinical characteristics of younger adults (under 60 years) without underlying comorbidities who died of COVID-19, so as to provide an implication for physician to identify the potential risk of poor clinical outcomes, as well as take timely prevention and treatment.
In this study, four patients had symptoms of digestive system including poor appetite, diarrhea, nausea and vomiting. Nevertheless, all patients had been reported decreases in albumin level in the early stages. The phenomenon of general digestive system involvement in severe patients was in accordance with previous studies. Wang et al found that patients admitted to the intensive care unit (ICU) were more likely to report abdominal pain, and anorexia [6]. In addition, Zhang et al reported nausea commonly experienced in severe group (P = 0.027) [7]. Guan W et al showed that the frequency of nausea or vomiting, diarrhea was 6.9%, 5.8% in severe patients, and 4.6%, 3.5% in nonsevere patients respectively [11]. They also demonstrated that severe and death patients have malnutrition caused by digestive symptom in the early stage. It is proposed that malnutrition may promote the development of the diseases, secondary severe infection and multiple organ failure, even if albumin rises at the end of the disease course. Thus, in the early stage of the disease, timely strengthen nutrition and improve digestive system symptoms should be considered to improve the poor prognosis.
Laboratory tests indicated that the levels of D-dimer, CK and CRP were remarkably higher than normal range. The levels of PCT, creatinine, leukocyte counts and neutrophil counts were gradually higher as disease progressed, which is in consistent with recently published results. Wang DW et al showed that, the neutrophil count, D-dimer, blood urea, and creatinine levels continued to increase over the disease progression in the nonsurvivors [6]. In addition, Cao et al reported D-dimer greater than 1 µg/mL at admission to hospital was associated with the risk of death [12]. Zhang et al reported that, higher values of leukocyte count (P = 0.014), D-dimer (P < 0.001), CRP (P < 0.001), PCT (P < 0.001) were found in severe cases, compared to non-severe cases [7]. The levels of hemoglobin gradually decreased as the development of the disease, which was consistent with the study of Chen et al [10]. The abnormal index of CRP, PCT, leukocyte counts and neutrophil counts may indicate sustained and prominent inflammatory response. The higher D-dimer but the lower hemoglobin levels may attribute to a disturbed coagulation mechanism under the condition of infection with COVID-19. In addition, higher leukocyte count and PCT may be due to secondary bacterial infection. Furthermore, the virus, hypoxia and shock may induce higher serum CK and creatinine levels.
In this study, our result shown an increase in the level of NRL in early stage of disease, and a gradual decrease as the disease progressing, in consistent with previously published studies which showed that [13, 14], NLR levels were significantly higher in non-survivors than in survivors with Community Acquired Pneumonia (CAP), the receiver operating characteristic (ROC) curve of NLR as a predictor of the mortality was better than that of the neutrophil count, white blood cell (WBC) count, lymphocyte count and CRP level. Therefore, the increase of NLR in early stage of disease may have predictive value for death. Nevertheless, the increase in lymphocyte counts was different from the previous studies [6, 12], but was consistent with the study of Kai et al [15], which found the proportion of lymphocytes decreased in elderly patients was much higher than that of the young and middle-aged patients, perhaps patients under the age of 60 in our study was without underlying diseases, which was different in patients in previous studies. In addition, the small sample size in our study may affect the accuracy of the results.
It takes about 9-12d from the initial symptoms to large range of ground-glass opacity in CT scan in our study, around which they were admitted to the intensive care unit. The first admission to hospitals appeared about 4-14d after the onset of the symptoms, which was similar to the previous studies. Li et al showed that 89% of patients not being hospitalized until at least day five of illness [16]. Zhou et al reported the median time from illness onset to hospital admission on non-survivor patients was 11.0 days (8.0–15.0) [12]. Their clinical status deteriorated rapidly. All patients underwent noninvasive ventilation. Five were further treated with invasive ventilation. ECMO was applied as the last resort to treat three patients. This reminds us to pay attention to the early stage of young and middle-aged patients without chronic underlying diseases, timely and effective therapies should be considered for the severe patients to prevent the deterioration of the disease.
Our study has several limitations. First, the patients who died of COVID-19 were mainly elderly patients with underlying diseases, the number of younger patients who died was less, which would bring limitations to the study sample. Second, we did not report the CT images about the disease progresses of patient 1, 4 and 5, patient 4 was also not included in the figure of the dynamic changes of laboratory parameters, which might cause bias. Third, some patients under 60 years with insufficient clinical data were excluded from the analysis. Therefore, our results may not be generalizable to all patients under 60 years. Fourth, this is only general treatment plans for confirmed patients in a single center hospital, it is necessary to explore specific treatment plans for younger patients without underlying diseases in multicenter studies. Whereas, we believe that the findings reported here are important for understanding the clinical characteristics of COVID-19 in middle-aged patients of high mortality risk.
Generally, there was an increase in lymphocyte counts in patients under 60 years old who died of the COVID-19 pneumonia, which was different from those older patients. In addition, the decreased level of serum albumin in the early course and delays in the first admission to hospital deteriorated the symptoms of the infection. The increase of NLR in early stage of disease might be a risk factor of death. To pay attention to the clinical information and take a timely therapeutic strategy for similar severe patients might be important for physicians to reduce mortality due to the COVID-19 pneumonia.