Clinical course and progression of severe and critically ill patients with corona virus disease 2019

BackgroundThe emergence of Corona Virus Disease 2019 (COVID-19) in Wuhan, China at the end of 2019 is a major public health issue, causing to a large global outbreak. However, the information regarding the clinical characteristic and progression of severe and critically ill patients with COVID-19 is scarce. Methods: We conducted a single-center, retrospective, observational study and enrolled 126 severe and critically ill adult patients who were admitted to the intensive care unit (ICU) of Tongji hospital, between Feb 1 and Feb 20, 2020. Results: Of 126 patients, 85 patients with the positive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included. The mean age of 85 patients was 68.3 (SD 10.5) years. More than half were men, 55 (62.4%) had chronic illness. 57 (66.3%) patients had died before Feb 28, 2020. the median duration from onset of illness to death, hospitalization to death and ICU admission to death were 22 (17.0-26.0) days, 9.0 (6.0-13.0) days and 5.0 (2.0-6.0) days, respectively. Compared with survivors, non-survivors were more likely old (69.6 [SD 10.22] vs 65.6 [10.9]). Furthermore, the non-survivors had higher white blood cell (WBC) and neutrophil count, neutrophil percentage, high-sensitive C-reactive protein (hs-CRP) and lower lymphocyte and platelet count, lymphocyte percentage and albumin. Notably, arbidol may improve the survival of severe and critically ill patients. Conclusions: Our study reveals the non-survivors had worse blood routine and other clinical monitors. Additionally, arbidol may play useful role in the survival of severe and critically ill patients, which needs further validation.


Introduction
Since Dec 8, 2019, cases of unidentified pneumonia emerged in Wuhan, Hubei province, 6 Differences on clinical data between survivors and non-survivors were compared using independent t-test or Mann-Whitney test for continuous data and chi-square test or the Fisher's exact test for categorical variables All statistical analysis was performed by the statistical software packages R (http://www.R-project.org, The R Foundation) and the EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) with a two-sided significance threshold of p < 0.05.

Demographic characteristic
As is shown in the flow chart (Fig. 1) The laboratory parameters of severe and critically ill patients with COVID-19 on admission were shown in Fig. 3. Compared with survivors, non-survivors were more likely accompanied by higher WBC (Fig. 3A) and neutrophil count (Fig. 3B), neutrophil percentage (Fig. 3F). Furthermore, the non-survivors were also characterized by severe lymphopenia (Fig. 3C and G) during hospitalization, so were albumin and platelet count.
Moreover, the liver and renal function were more likely worse in non-survivors, as manifested by higher levels of alanine aminotransferase (ALT, Fig. 3H), aspartate aminotransferase (AST, Fig. 3I), blood urea nitrogen (BUN, Fig. 3M) and creatinine ( Fig. 3N) in the serum originated from non-survivors cohort. However, the ratio for AST and ALT was no detected perceptible differences between non-survivors and survivors ( Fig. 3J), so was the ratio for BUN and creatinine (Fig. 3O).
It was noted that the levels of brain natriuretic peptide (BNP) underwent a steady decrease during hospitalization in both survivors and non-survivors, indicating that cardiac failure of the patients was improved after treatment (Fig. 3S). According to previous data, sepsis was one of important reasons for the death of patients with COVID-19 [6,7]. Indeed, compared with survivors, an increasing trend was existed for hs-CRP  (Table 3).

Discussion
In the last two decades, coronavirus has caused two large-scale pandemics, severe acute respiratory syndrome (SARS) in 2002 [8,9] and the Middle East respiratory syndrome (MERS) in 2012 [10,11]. Recently, a novel coronavirus, SARS-CoV-2, induced an outbreak died of multiple organ failure. We observed the median time from admission to death, from onset to death, from ICU admission to death were 9, 22, 5 days. These periods were very short. If the patients did not admission to hospital or ICU in time, they may have no chance to reverse disease. In non-survivors, 52.6% patients are older than 70-year and 68.4% patients are male. It indicated that old, male patients are more likely than others to die.
Most patients in our study had fever, cough, and dyspnea prior to admission, the other symptoms include fatigue, diarrhea, myalgia, headache, confusion, vomiting, abdominal pain, chest pain, dizziness, hemoptysis, sore throat. It was noted that the percent of dyspnea is much higher than previous studies[1, 6], indicating that dyspnea may be the premonitory symptom for severe and critically ill patients and more attention should be paid.
Notably, no perceptible differences were observed for blood routine examination between survivors and non-survivors at admission. However, with the disease progress, we found neutrophil percentage of non-survivors was always more than 90% from 3 days after admission, while that of survivors underwent a steady decrease, and reduce to 81.8% at 18 days after admission, indicating the percentage of neutrophil maybe a key predictor of death. Furthermore, non-survivors were more likely accompanied by lymphopenia than the survivors during hospitalization, which were comparable with other COVID-19 studies [1,17]. For liver and renal function, the non-survivors seem have more liver and renal injury,