The characteristics of laboratory tests at admission and the risk factors for adverse clinical outcomes of severe and critical COVID-19 patients

In December 2019, a cluster of patients with pneumonia of unknown etiology was identified in Wuhan City, Hubei Province, China. Isolation of bronchoalveolar-lavage samples from patients with pneumonia in human airway epithelial cells and subsequent whole-genome sequencing revealed the presence of a novel beta-coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1], and the viral disease was officially named coronavirus disease 2019 (COVID-19) on February 12, 2020 [2]. The virus spread internationally at a rapid rate within a month after its first identification; and the virus is mostly transmitted through respiratory droplets and close contact with infected people [3]. Severe acute respiratory syndrome (caused by SARS-CoV) [4‐6], which occurred in 2003, and Middle East respiratory syndrome coronavirus (MERS -CoV), which occurred in 2013, belongs to the same beta-coronavirus genus of coronaviruses as SARS-CoV-2 [7, 8]. They are highly pathogenic and the infection manifests as a severe acute respiratory disease [9]. According to bioinformatics prediction methods and in vitro experiments, it was found that the virus may attach to host cells through the human angiotensin-converting enzyme 2 (ACE2) receptor found primarily in airway epithelial cells [10, 11].

To date, more than 2 million deaths of the pandemic and huge economic and social upheaval internationally [12]. There is no effective therapy for COVID-19,vaccine is the best defense against COVID-19. In order to explore the onset of clinical characteristics of COVID-19 and assess the prognostic risk factors for patients, we conducted laboratory tests for 446 patients, evaluated the short-term results, and tried to identify the possible clinical consequences and final outcome of the patients.

This retrospective study identified risk factors for death in severe and critical COVID-19 patients. We included 446 patients with COVID-19 in this study, and 20.2% of them showed a high mortality rate. As the disease is still in epidemic, our research cannot reflect the final mortality. In the study we found that both older age and higher white blood cell count were highly significant independent risk factors for death in hospitalized patients with COVID-19. In patients’ age more than 60 years, the death rate was significantly high. A study shows that humoral and cellular immune functions decline with age [14]. As the virus attacks the body, older people has an increased risk of death due to reduced immunity and the presence of co-morbidities. Zhou et al. [15] also reported that older age was an important independent risk factor for COVID-19 patients. We further divided all patients into different age groups (Fig. 3) and displayed the mortality trend over different age groups. From Fig. 3, we can observe an increasing trend of mortality as age increases. For patients who were at least 75 years old, the mortality rate is very high compared to other age groups. Note that there is only 1 out of 4 patients died in the age group 18–19. Due to small sample size, the interpretation should be in caution.

Results of laboratory tests demonstrated that higher white blood cell (WBC) count was a highly significant independent risk factor for mortality in severe and critical COVID-19 patients. We further divided the WBC into 10 deciles and calculate the Pearson correlation between mortality and the WBC count within each decile. By doing this, we expected to find out the association between mortality and WBC count. The results showed that the highest decile of WBC count has a correlation of 0.39 with mortality while the association in the other deciles were much lower. An elevated white blood cell counts often indicates an ongoing inflammatory responses to bacterial infection or disease progression. Patients with severe virus infection were more likely to co-infected with bacteria due to low immune functions. In other coronavirus infections such as SARS-CoV and MERS-CoV, could found “bcytokine storms” and immunopathology. Excessive inflammation could occur while immune response was dysregulated. The inflammatory response could stimulate the production of inflammatory cells and speed up the apoptosis of lymphocytes [16]. Patients with MERS found lower leukocyte and neutrophil counts, had signifcantly lower hazard ratios for mortality [17]. Recent study has reported that neutrophil-to-lymphocyte ratio was an independent risk factor for determining the in-hospital mortality in COVID-19 [18]. Therefore, we should pay attention to the indicators of inflammatory response at an early stage of the disease. White blood cell counts could be quickly obtained based on a routine blood routine test on admission, that may aid clinicians identify high-risk COVID-19 patients at an early stage. and administer combined antibacterial and antiviral therapy.

Some studies based on the characteristics of patients [15, 19, 20], showed a similar median age of onset of COVID-19. A few studies also revealed that men were more susceptible to COVID-19 [19‐21]. Our study did not demonstrate significant gender differences, but in terms of patient mortality rate, males were at a higher risk of contracting COVID-19 than females, possibly due to a stronger innate and adaptive immune system providing resistance to viral infections in females [22‐25].

Although the lymphocyte count of most patients was low [26‐28], it was not found to be an independent risk factor in this study. The median lymphocyte count in patients who later died was significantly lower than that in surviving patients. Hence, lymphopenia might be related to viral invasion of the immune system leading to immune damage.

Prior to the first outbreak of SARS, a limited number of coronaviruses, causing only mild illnesses such as the common cold, were known to infect in humans [29]. Given the high prevalence, widespread distribution, extensive genetic diversity, and frequent genomic recombination of coronaviruses, it is likely that new coronaviruses will be regularly identified owing to frequent cross-species infections and occasional spillover events that occur in nature [30]. In the past two decades, major infectious diseases caused by coronaviruses included SARS, MERS, and the recent COVID-19. Therefore, it is necessary to follow up on the dynamics of this disease over time to have a better understanding of its pathogenesis and treatment strategies.

Our study has several limitations worth noting. Firstly, there was insufficient information on demographic characteristics, clinical symptoms, history of exposure, and personal history of the patients included in this study. Secondly, it was a retrospective study design and relied on data collected from case records. Information such as which patient comes from which hospital was not collected. There might be intracluster correlations among four hospitals, although we believe the impact on standard errors is minimal. Thirdly, the patients did not undergo all laboratory tests like neutrophil count, lactate dehydrogenase and serum ferritin tests. Therefore, their role might be underestimated in predicting death in hospitalized patients. Lastly, we studied a short-term prognosis of patients during hospitalization, however, SARS-CoV-2 is a newly discovered virus, and its onset, characteristics and prognosis are still being researched. So the validity of the risk factors for mortality derived from our cohort remains tentative, and we need a larger sample size and a longer follow-up period to validate our findings. In the later stages, follow-up of surviving patients must also be continued to better understand clinical course of the disease.

The COVID-19 outbreak has been declared a global pandemic. In this study, we found that older age and higher white blood cell count were clinically useful independent risk factors for mortality of severe and critical COVID-19 patients in hospitalized. We hope this information will aid clinicians in the treatment of patients with COVID-19.