Retrospective analysis of the effect of current clinical medications and clinicopathological factors on viral shedding in COVID-19 patients.

BIOMEDICAL REPORTS 13: 68, 2020 Retrospective analysis of the effect of current clinical medications and clinicopathological factors on viral shedding in COVID‑19 patients YANFENG PAN1*, QINGQING LI1*, XUE YU1*, QIANKUN LUO2*, TAO QIN2*, NINGBO XIN3, QIAN ZHANG4, XIANYANG LI5, XINWEI DU6, QINGXIA ZHAO3 and LI SUN7 1 Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University; Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital; 3Department of Infectious Diseases, Zhengzhou Sixth People's Hospital; 4 Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Henan 450000; 5 Department of Infectious Diseases, Shenqiu County People's Hospital, Zhoukou, Henan 466300; 6 Department of Infectious Diseases, The People's Hospital of Suzhou New District, Suzhou, Jiangsu 205011; 7 Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China 2 Received June 13, 2020; Accepted September 23, 2020 DOI: 10.3892/br.2020.1375 Abstract. The aim of the present study was to identify the risk factors associated with prolonged shedding in patients with coronavirus disease 2019 (COVID‑19), and to evaluate the effects of current clinical and clinicopathological factors on viral shedding in patients. A total of 186 COVID‑19 inpatients were enrolled in this multicentre retrospective analysis. Detailed clinical data of each patient were collected, and the factors that affected the duration of viral shedding were retrospectively analysed. The median duration of viral shed‑ ding in the 186 COVID‑19 patients was 13 days. The median duration of viral shedding was 12 days in non‑severe patients, and 17 days in severe patients, and there was a significant difference between the two groups (P<0.001). Multi‑factor regression analysis suggested that the onset‑hospitalization Correspondence to: Professor Yanfeng Pan, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Jinshui, Zhengzhou, Henan 450000, P.R. China E‑mail: Professor Tao Qin, Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7 Weiwu Road, Jinshui, Zhengzhou, Henan 450000, P.R. China E‑mail: * Contributed equally Key words: COVID‑19, SARS‑CoV‑2, viral shedding, lopinavir/ ritonavir, corticosteroid interval [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.15‑1.41; P<0.001] and comorbidity with a chronic disease (OR, 2.43; 95% CI, 1.14‑5.17; P=0.021) were independent risk factors for prolonged viral shedding, whereas lopi‑ navir/ritonavir (LPV/r) was an independent protective factor (OR, 0.28; 95% CI, 0.11‑0.75; P=0.011). Spearman's rank correlation analysis showed that the onset‑drug interval was positively correlated with the duration of viral shedding (r=0.446; P<0.0001). Umifenovir, and low and short courses of glucocorticoids were not associated with prolonged viral shed‑ ding. The prolonged viral shedding was the initial causative factor of persistent aggravation of the patient's conditions. The interval between presentation of symptoms and hospitalization as well as complications with a comorbid chronic disease were independent risk factors for prolonged viral shedding. LPV/r shortened the duration of viral shedding, and the smaller the interval between presentation and LPV/r onset was, the faster viral shedding occurred. Introduction Coronavirus disease 2019 (COVID‑19), caused by infection from severe acute respiratory syndrome‑coronavirus 2 (SARS‑CoV‑2), has become a global pandemic and a serious global public health emergency (1). The prevention and control of COVID‑19 is a considerable challenge being faced by numerous governments worldwide, and this is complicated by the high transmission efficiency, high mortality rate, general susceptibility of the population, and the absence of effective drugs and vaccines (2,3). As the pathology of COVID‑19 is similar to that of Middle East respiratory syndrome coronavirus (MERS‑CoV) and SARS‑CoV infection (4,5), drugs identified to be effective for these previous diseases, as well as antivirals screened from in vitro experiments, are 2 PAN et al: EFFECT OF CLINICAL MEDICATIONS AND CLINICOPATHOLOGICAL FACTORS ON SARS-CoV-2 SHEDDING being assessed or used clinically without sufficient clinical evidence. These drugs include IFN‑α and ribavirin, as well as lopinavir/ritonavir (LPV/r) and Umifenovir as antiviral drugs. Several studies have described the effects of antiviral on the duration of viral shedding (6‑8) and other studies have assessed the differences in the duration of viral shedding between patients with different degrees of severity of infec‑ tion (9). Recently, obesity was identified as a risk factor for increased COVID‑19 prevalence, severity and lethality (10), and modulation of zinc status may be beneficial in the management COVID‑19 (11). However, these studies did not consider the effects of both clinical and clinicopathological factors on the duration of viral shedding. In the present study, detailed data on inpatients with definite clinical outcomes between January 20, 2020 and March 20, 2020 was collected and reviewed the duration of viral shedding in COVID‑19 infected patients in order to evaluate the impact of current clinical and clinicopathological factors on viral shedding. Clinicopathological factors refers to the patient's general characteristics and medical history that are not related to this hospitalization, such as sex, age, comorbid chronic diseases and onset‑hospitalization interval. Materials and methods Study design. Data on SARS‑CoV‑2 nucleic acid‑positive hospitalized patients were collected between January 20, 2020 and March 20, 2020. Reverse transcription polymerase chain reaction (RT‑PCR) was used to test for SARS‑CoV‑2 nucleic acids from respiratory tract secretions and throat swab speci‑ mens. The patients underwent a RT‑PCR test every 3 days during the first week of hospitalization, and a nucleic acid test every day after a week of hospitalization. A retrospective analysis of the SARS‑CoV‑2 shedding duration and the effect of currently used drugs on the duration of viral shedding was performed. This study was exempt from the need to obtain patient consent due to the retrospective nature of the study, and was approved by the Medical Ethics Committee of Zhengzhou University (approval no. 2020‑KY‑162). Data collection. The age, sex, clinical symptoms, onset‑drug inter val, onset‑hospitalization inter val, therapeutic drugs and prognosis of each patient were collected. The median age of the 186 patients was 46.5 years (age range, 5‑94 years). A total of 105 (56.5%) cases were males and 81 (43.5%) were females. Onset was defined as the earliest time when clinical symptoms appeared. The duration of viral shedding was de (...truncated)