Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in patients with SARS-CoV-2 infection

Abstract

Background: The duration of viral shedding is central to guide decisions around isolation precautions and antiviral treatment. However, studies about risk factors associated with prolonged SARS-CoV-2 shedding and the potential impact of Lopinavir/Ritonavir (LPV/r) treatment remain scarce. Methods: In this retrospective study, data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had RT-PCR conversion at the NO.3 People's hospital of Hubei province between 31 January and 09 March 2020. We compared clinical features and SARS-CoV-2 RNA shedding between patients with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate risk factors associated with prolonged viral shedding. Results: Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (IQR, 18-32 days). Older age (odd ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05, p=0.03) and lack of LPV/r treatment (OR 2.42, 95% CI 1.10-5.36, p=0.029) were independent risk factors for prolonged SARS-CoV-2 RNA shedding in multivariate logistic regression analysis. The median duration of viral shedding was shorter in the LPV/r treatment group (n=78) than that in no LPV/r treatment group (n=42) (median, 22 days vs. 28.5 days, p=0.02). Only earlier administration of LPV/r treatment (≤10 days from symptom onset) could shorten the duration of viral shedding. Conclusions: Older age and lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with COVID-19. Earlier administration of LPV/r treatment could shorten viral shedding.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

“…One retrospective study [54] included 78 patients with COVID-19 infection with lopinavir-ritonavir and 42 without lopinavir-ritonavir (non-critical patients). The median time of positive-to-negative conversion of RT-PCR test in the lopinavir-ritonavir group was shorter than the control group (22 (IQR, 18-29) days vs. 28.5 (IQR, 19.5-38) days, P = 0.02) within 10 days, and did not show a significant difference > 10 days (median27.5 days vs. 28.5 days, P = 0.86).…”

Clinical evaluation of selected Pharmacological Treatments used for Coronavirus (COVID-19) pandemic

“…Five patients in the lopinavir-ritonavir group experienced adverse events (gastrointestinal and deranged liver function), whilst no adverse events occurred in the Umifenovir or control groups. Another clinical trial of 120 patients in China, (20) 78 patients (65%) recieved lopinavir-ritonavir treatment and were categorized as severe COVID-19 . they had a higher ratio of lymphocyte count <0.8×109/liter than those without lopinavir-ritonavir treatment.…”

Treatment Options for Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, and Coronavirus Disease 2019: a Review of Clinical Evidence

“…In another retrospective study of 323 patients in Wuhan, LPN/r was more given to critical patients (46.2%) than non-critical cases (5.4%) and more administered in unfavorable than favorable outcomes (23.8% vs. 5.0%) [56]. Furthermore, treatment with LPN/r was reported to be independently associated with the prolongation of virial RNA shedding (OR = 2.42, 95% CI = 1.10 -5.36) and earlier provided LPN/r might shorten the viral shedding as well (22 days vs. 28.5 days, P = 0.02) [68]. Findings from the efficacy of lopinavir plus ritonavir and arbidol against novel coronavirus infection (ELACOI) trial also suggested the little benefit improvement of LPV/r in clinical outcomes among non-severe patients, compared with supportive care [57].…”