Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection

Abstract

BackgroundThe duration of viral shedding is central to the guidance of decisions about isolation precautions and antiviral treatment. However, studies regarding the risk factors associated with prolonged shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of lopinavir/ritonavir (LPV/r) treatment on viral shedding remain scarce.MethodsData were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had reverse transcription PCR conversion at the No. 3 People's Hospital of Hubei province, China, between 31 January and 9 March 2020. We compared clinical characteristics and SARS-CoV-2 RNA shedding between patients initiated with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate the risk factors associated with prolonged viral shedding.ResultsOf 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 (interquartile range 18–32 days). Older age (OR 1.03, 95% CI 1.00–1.05; p=0.03) and the 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. Patients who initiated LPV/r treatment within 10 days from symptom onset, but not initiated from day 11 onwards, had significantly shorter viral shedding duration compared with those without LPV/r treatment (median 19 days versus 28.5 days; log-rank p<0.001).ConclusionOlder age and the lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). Earlier administration of LPV/r treatment could shorten viral shedding duration.

Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study

“…On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were identified as risk factors for prolonged viral shedding in this study, consistent with previous studies ( Fu et al, 2020 , Yan et al, 2020a , Yan et al, 2020b , Zhou et al, 2020 ). Old age, comorbidities, and steroid use might blunt the host immune response, thereby promoting viral replication.…”

“…When analyzing the effect of antiviral agents, the timing of antiviral therapy is an important issue to be considered. Early (within 7 days from symptom onset) initiation of antiviral therapy may be critical in reducing SARS-CoV-2 viral load, as previously noted ( Fu et al, 2020 , Keyaerts et al, 2004 , Yan et al, 2020a , Yan et al, 2020b ). Due to the limitation of our database, it was difficult to know the initiation timing of antiviral treatment in each individual patient; however, the government of South Korea had launched a series of aggressive measures to perform tight contact tracing and mass screening tests, which enabled early diagnosis within 3–5 days from symptom onset ( Ryu et al, 2020 ).…”

Temporal profile and determinants of viral shedding and of viral clearance confirmation on nasopharyngeal swabs from SARS-CoV-2-positive subjects: a population-based prospective cohort study in Reggio Emilia, Italy.

“…28 This study also observes an increase in time to viral clearance with greater disease severity, with increasing age and in the absence of antiviral therapy. 28 A recent case report states that viral shedding was detected up to 49 days from symptom onset. 29 As Atkinson and Petersen discuss, to be able to use these results to make public health decisions, it must be remembered that RT-PCR can identify even fragments of the virus, meaning that subjects who do not have any active replication and are thus not infectious will nevertheless test positive.…”

Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients

“…Mild cases may have an earlier viral clearance (i.e., negative real-time polymerase chain reaction (RT-PCR) or cell cultures by day 10 post onset) [1,3], whereas severe cases may have longer viral shedding [4,5]. Most studies focused on nasopharyngeal or oropharyngeal swabs [3,4,[6][7][8][9] and did not consider lower respiratory samples. Most importantly in this context, only one study (until June 2020) assessed the infectivity with cell culture for SARS-CoV-2 [1].…”