Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period
Muhammad Vitanata Arfijanto, Tri Pudy Asmarawati, Bramantono Bramantono, Musofa Rusli, Brian Eka Rachman, Bagus Aulia Mahdi, Nasronudin Nasronudin, Usman Hadi
Pathophysiology, doi:10.3390/pathophysiology30020016
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.
Conflicts of Interest: The authors declare no conflict of interest.
References
Aghili, Ebrahimpur, Arjmand, Shadman, Pejman Sani et al., Obesity in COVID-19 era, implications for mechanisms, comorbidities, and prognosis: A review and meta-analysis, Int. J. Obes,
doi:10.1038/s41366-021-00776-8Aly, Rahman, Ahmed, Alghamedi, Al Shehri et al., Indicators of Critical Illness and Predictors of Mortality in COVID-19 Patients, Infect. Drug Resist,
doi:10.2147/IDR.S261159Asmarawati, Rosyid, Suryantoro, Mahdi, Windradi et al., The clinical impact of bacterial co-infection among moderate, severe and critically ill COVID-19 patients in the second referral hospital in Surabaya,
doi:10.12688/f1000research.31645.1Asmarawati, Suryantoro, Rosyid, Marfiani, Windradi et al., Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit, Indian J. Crit. Care Med,
doi:10.5005/jp-journals-10071-24170Bitker, Dhelft, Chauvelot, Frobert, Folliet et al., Protracted viral shedding and viral load are associated with ICU mortality in Covid-19 patients with acute respiratory failure, Ann. Intensiv. Care,
doi:10.1186/s13613-020-00783-4Buetti, Trimboli, Mazzuchelli, Priore, Balmelli et al., Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients, Endocrine,
doi:10.1007/s12020-020-02465-4Burhan, Susanto, Isbaniah, Sally, Eka et al., Pedoman Tatalaksana COVID-19
Chen, Tsai, Yu, Cheng, Yeh, Prolonged viral shedding and new mutations of COVID-19 could complicate the control of the pandemic,
doi:10.1099/acmi.0.000133Codo, Davanzo, De Brito Monteiro, De Souza, Muraro et al., Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis, Cell Metab,
doi:10.1016/j.cmet.2020.07.007Cunha, Vilela, Molina, Acuna, Muxel et al., Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient, Front. Med,
doi:10.3389/fmed.2021.760170Feng, Li, Yao, Yu, Zhou et al., Clinical Factors Associated with Progression and Prolonged Viral Shedding in COVID-19 Patients: A Multicenter Study, Aging Dis,
doi:10.14336/AD.2020.0630Langford, So, Raybardhan, Leung, Westwood et al., Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis, Clin. Microbiol. Infect,
doi:10.1016/j.cmi.2020.07.016Leung, Chorlton, Tyson, Al-Rawahi, Jassem et al., COVID-19 in an immunocompromised host: Persistent shedding of viable SARS-CoV-2 and emergence of multiple mutations: A case report, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2021.10.045Li, Cao, Chen, Cai, Zhang et al., Duration of SARS-CoV-2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID-19, J. Med. Virol
Menghua, Xin, Jianwei, Yu, Qinwei, Case report: One case of coronavirus disease 2019 (COVID-19) in a patient co-infected by HIV with a normal CD4+ T cell count, AIDS Res. Ther,
doi:10.1186/s12981-020-00301-3Muhamad, Ugusman, Kumar, Skiba, Hamid et al., COVID-19 and Hypertension: The What, the Why, and the How, Front. Physiol,
doi:10.3389/fphys.2021.665064Nugroho, Suryantoro, Yuliasih, Rosyid, Asmarawati et al., Optimal use of tocilizumab for severe and critical COVID-19: A systematic review and meta-analysis,
doi:10.12688/f1000research.45046.1Pradhan, Olsson, Sex differences in severity and mortality from COVID-19: Are males more vulnerable?, Biol. Sex Differ,
doi:10.1186/s13293-020-00330-7Qi, Yang, Jiang, Tu, Wan et al., Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: A retrospective cohort study, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.05.045Ryoo, Kim, Sohn, Seo, Oh et al., Factors promoting the prolonged shedding of the pandemic (H1N1) 2009 influenza virus in patients treated with oseltamivir for 5 days, Influenza Other Respir. Viruses,
doi:10.1111/irv.12065Soegiarto, Wulandari, Purnomosari, Dhia Fahmita, Ikhwan Gautama et al., Hypertension is asso-ciated with antibody response and breakthrough infection in health care workers following vaccination with inactivated SARS-CoV-2, Vaccine,
doi:10.1016/j.vaccine.2022.05.059Wang, Zhang, Sang, Ye, Ruan et al., Kinetics of viral load and antibody response in relation to COVID-19 severity, J. Clin. Investig,
doi:10.1172/JCI138759Wibisono, Hadi, Bramantono Arfijanto, Rusli, Rahman et al., National early warning score (NEWS) 2 predicts hospital mortality from COVID-19 patients, Ann. Med. Surg,
doi:10.1016/j.amsu.2022.103462Xu, Chen, Yuan, Yi, Ding et al., Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19), Clin. Infect. Dis,
doi:10.1093/cid/ciaa351Yousaf, Hameed, Alsoub, Khatib, Jamal et al., COVID-19: Prolonged viral shedding in an HIV patient with literature review of risk factors for prolonged viral shedding and its implications for isolation strategies, Clin. Case Rep,
doi:10.1002/ccr3.3786Zhang, Hu, Luo, Fang, Chen et al., Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. J. Clin. Virol,
doi:10.1016/j.jcv.2020.104364Zhang, Zhu, Ye, Hu, Zheng et al., Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection, J. Clin. Lab. Anal,
doi:10.1002/jcla.23923Zhou, She, Wang, Ma, Duration of Viral Shedding of Discharged Patients With Severe COVID-19, Clin. Infect. Dis,
doi:10.1093/cid/ciaa451Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan
Zhou, Zhang, Ren, Sun, Yu et al., Impact of age on duration of viral RNA shedding in patients with COVID-19, Aging,
doi:10.18632/aging.104114
