Our study enrolled 1087 patients with COVID-19 who were registered from centers of Sichuan and Wuhan provinces, where the outbreak risk levels were different. In the initial study, based on patient demographic and clinical characteristics obtained on the first admission, we established and validated a nomogram for predicting the risk for admission to ICU through LASSO and logistic regression analyses. The independently statistically significant factors included in the prediction model were age, respiratory rate, systolic blood pressure, smoking status, fever, and CKD. The validation of the model using different statistical methods demonstrated its optimal performance. As those factors can be obtained easily on admission, the nomogram is a convenient and valuable clinical warning tool to predict ICU admission of a patient with COVID-19, especially in the emergency department and even in a community health center.
Most patients with COVID-19 have mild disease with a good prognosis, but some patients may develop severe respiratory distress syndrome and have a poor prognosis [19]. To mitigate the burden on the healthcare system and provide the best care for patients, it is necessary to effectively predict the prognosis of the disease [20]. A predictive model that combines multiple variables or features to estimate the risk of poor outcomes of an infected person can assist the healthcare staff in classifying the patient's disease severity when allocating limited medical resources[21]. Previous studies have reported prediction models for diagnosis and prognosis of COVID-19 and for detecting the risk of being admitted to a hospital for COVID-19. Chen et al. constructed a diagnosis prediction model with 10 clinical factors based on 136 participants[22]. Wang et al. enrolled 296 in-hospital patients with COVID-19 and developed a clinical model to predict the mortality of such patients[20]. Dong et al. developed a scoring model to predict the progression risk with COVID-19 pneumonia on the basis of 209 patients[23]. However, those proposed models are poorly reported and have a high risk of bias, raising concern of possible unreliable predictions when applied in daily practice for diagnosing. In a recent study, a risk score was reported to estimate the risk of critical illness of patients with COVID-19 based on 10 variables[24]. Although the study had modest sample size and satisfying performance, the scoring system was complicated with some laboratory examination data that cannot be obtained before admission or quickly after admission. It is, therefore, necessary to develop and validate a convenient prediction model for healthcare staff or emergency staff that can be used quickly and easily. In our study, we constructed a warning model for predicting the risk of ICU admission on the basis of multi-center data from different cities and different severities of the outbreak in the Wuhan and Sichuan provinces. In our model, the independently statistically significant factors were age, respiratory rate, systolic blood pressure, smoking status, fever, and comorbidity with CKD, which could be obtained quickly, easily, practically, and reliably. This prediction model could be used in prehospital care or emergency department, allowing the medical staff to intervene at an early stage and determine their treatment location and the type of intervention. Statistically, our model demonstrated good discriminative ability and potential clinical benefit.
The model identified that comorbidities play a key role in the prognosis of patients with COVID-19. Cardiovascular system disease, especially hypertension, has been reported to be one of the most important independent risk factors[25]. In this study, we observed the patients with CKD were more likely to be admitted to the ICU, and that kidney disease was an independent risk factor for ICU admission of patients with COVID-19. This finding suggested that patients with a comorbidity of kidney disease on admission possibly had a high risk of deterioration[26, 27]. Previous studies revealed that kidney injury was associated with an increased risk of death in patients with influenza A virus subtype H1N1 and Severe acute respiratory syndrome (SARS). Multiple organ involvement, including the liver, gastrointestinal tract, and kidneys, has been reported during SARS in 2003 and very recently in patients with COVID-19[28-31]. We hypothesized that such patients could have a proinflammatory state with functional defects in innate and adaptive immune-cell populations and were known to have a higher risk for upper respiratory tract infection and pneumonia. The 2019-nCoV itself may also cause kidney injury through multiple mechanisms: the 2019-nCoV may use angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor and exert direct cytopathic effects on the kidney tissue. It has been reported ACE2 expression in the kidneys was nearly 100-fold higher than in the lungs[31]. Viral antigens or virus-induced specific immune effect mechanisms (specific T-cell lymphocytes or antibodies) and deposits of the immune complexes may damage the kidneys[32]. Early detection and treatment of renal abnormalities, including assessing the volume status and renal transplantation pressure, avoidance of nephrotoxic drugs, and adequate hemodynamic support, may help improve the vital prognosis of patients with COVID-19.
In most prognostic prediction models that have been published, older age, comorbidities, and increases in lactate dehydrogenase, lymphocyte, and C-reactive protein levels were the risk factors for poor prognosis[23]. Other indicators such as heart rate; breath rate; oxygen saturation; levels of procalcitonin, direct bilirubin, albumin, and D-dimer levels; activated partial thromboplastin time; glomerular filtration rate; and chest radiography abnormality have controversial conclusions[33, 34]. Our study also demonstrated that patients with COVID-19 infection who were older (especially >65 years) had a worse prognosis than younger patients. In our study, fever (training cohort, 63.0%; validation cohort, 66.0%), cough (training cohort, 59.8%; validation cohort, 65.1%), and fatigue (training cohort, 37.1%; validation cohort, 38.3%) were the most common symptoms. However, among all the symptoms, only fever was an independent risk factor for prognosis, which is different from other studies. The difference in the inconsistencies of these models could be attributed to the risk of bias caused by the sample size and geographical differences of each model.
Our study has certain limitations. First, the study design was retrospective in nature. Second, some patients had incomplete data on symptoms, laboratory test results, and imaging examination results, due to the variation in the structure of electronic databases across different participating hospitals and an immediate data extraction schedule. Third, the sample size was relatively small, warranting future studies with larger sample sizes to validate our results. Fourth, patients with severe disease were older than those with non-severe disease, implying that this difference in age could have been a confounding factor. Fifth, although this was a multi-center study, the results cannot be generalized to other populations. Sixth, we did not collect treatment-related data that may be critical to a patient's outcome. However, all patients received treatment in accordance with the guidelines issued by the National Health Commission of China.