key: cord-0941552-g64i23zw
authors: Liu, Ying; Li, Min; Liu, Dan; Luo, Jian Fei; Li, Nian; Zhang, Xuan; Tang, Xiao Ju; Zhang, Xin; Liu, Jia; Wang, Ji; Wang, Ting; Zhou, Yong Zao; Luo, Wen Xin; Liang, Zong An; Luo, Feng Ming; Li, Wei Min; Wang, Gang
title: Developing a multivariable risk prediction model to predict prolonged viral clearance in patients with COVID-19
date: 2020-12-31
journal: J Infect
DOI: 10.1016/j.jinf.2020.12.026
sha: 25a57a0e85c73bb788b480781bc147c5d3868047
doc_id: 941552
cord_uid: g64i23zw

• In this study, a multivariable risk prediction model was developed that may help predict a patient's risk of prolonged SARS-CoV-2 RNA clearance. • Time from illness onset to admission, haemoptysis, diarrhea, use of glucocorticoids, leukopenia and elevated alanine transaminase were independent risk factors for prolonged duration of viral clearance; • Estimating these risk factors could promote individual precision therapy and optimizing the use of medical resources.

We read with interest of the recent article in your journal about the viral load and infectivity over the course of an SARS-CoV-2 infection 1 , which has showed that there is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain. Therefore, it is of great significance to explore the duration of viral clearance and related factors, which may have important implication for making clinical decisions regarding the isolation precautions and treatment in patients with COVID-19 2, 3 .

We did this retrospective study to explore risk factors associated with viral clearance and to develop a risk prediction model to help identify patients who are likely to have prolonged duration viral clearance based on two cohorts of Chinese discharged patients with COVID-19. We collected the epidemiological, clinical symptoms and signs, laboratory findings, treatments and outcomes data from the hospital electric medical records based on two cohorts led by the Sichuan and Wuhan Collaboration Research Group for COVID-19, China. The least absolute shrinkage and selection operator (LASSO) and logistic regression analysis was used to develop the multivariable risk prediction model. Our results found that older age was independently associated with prolonged duration of virus clearance, which was supported by previous study 4 . Older age has been proved to be associated with poor clinical outcomes in COVID-19 patients 5 .

Innate and adaptive immune are largely compromised with aging, resulting in limiting the viral clearance and host inflammatory responses. At the same time, our results demonstrated that delayed hospital admission was associated with prolonged duration of virus clearance, which was also proved by the study of Xu et al 6 Besides, hemoptysis has been described as an infrequent COVID clinical symptom by several retrospective analysis, which may indicate the venous thrombosis, particularly pulmonary embolism. As to the lab findings, our study found that the peripheral blood white count, especially lymphocyte count was relatively lower in patients with prolonged duration of viral clearance. The SARS-CoV-2 caused lymphocytic depletion in infected patients 3 , and the mechanism may be caused by direct attack of coronavirus on lymphocytes or by immune-mediated apoptosis of lymphocytes, which may infect the capacity to clear the virus. In addition, we also found that ALT was increased in the prolonged duration of viral clearance group, indicated hepatic dysfunction was associated with prolonged duration of viral clearance. The recent systematic review and meta-analysis has also indicated that patients with COVID-19 have a higher than expected prevalence of liver injury, and the extent of the injury is associated with the severity of the disease 8 . However, the underlying mechanism and its association with viral clearance require more studies to elucidate Glucocorticoids have been widely used in conjunction with other drugs to treat patients infected with SARS-CoV-2. However, current interim guidance from WHO on clinical management opinions for the COVID-19 advises against the use of corticosteroids unless indicated for another reason 9 as the use of glucocorticoids may delay the clearance of viral nucleic acids in patients with MERS and SARS 10 . Our study further demonstrated that the usage of systemic GCs was independently associated with a delay in viral clearance in discharged COVID-19 patients, most of which were mild or general patients. Therefore, glucocorticoid treatment is not recommended for patients with COVID-19, especially for mild disease.

In conclusion, prolonged duration of viral clearance was independently associated with older age, prolonged time from illness onset to admission, haemoptysis, diarrhea, use of glucocorticoids, leukopenia and elevated alanine transaminase. Estimating these risk factors could help identify patients who are or are not likely to develop prolonged duration of viral clearance, which could promote individual precision therapy and optimizing the use of medical resources. 

SARS-CoV-2 detection, viral load and infectivity over the course of an infection

The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Factors Associated With Prolonged Viral Shedding and Impact of Lopinavir/Ritonavir Treatment in Hospitalised

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Factors Associated With Prolonged Viral RNA Shedding in Patients With COVID-19

Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19

A systematic review and meta-analysis of the COVID-19 associated liver injury

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

Corticosteroid therapy for critically ill patients with middle east respiratory syndrome