Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection

Wang, Yeming; Guo, Qiang; Zheng, Yan; Zhou, Daming; Zhang, Wei; Zhou, Shujun; Li, Yuping; Yuan, Jing; Uyeki, Timothy M.; Shen, Xinghua; Wu, Wenjuan; Zhao, Hui; Wu, Yunfu; Shang, Jia; He, Zhengguang; Yang, Yi; Zhao, Hongsheng; Hong, Yongqing; Zhang, Zehua; Wu, Min; Wei, Tiemin; Deng, Xilong; Deng, Yong-Qiang; Cai, Lihua; Lü, Weihua; Shu, Hongmei; Zhang, Lin; Luo, Hong; Zhou, Yan; Weng, Heng; Song, Kun; Yao, Li; Jiang, Mo; Zhao, B; Chi, Ruibin; Bo-qi, Guo; Fu, Lin; Yu, Li; Min, Haiyan; Chen, Pu; Chen, Shuifang; Hong, Lei; Mao, Wei; Huang, Xiaoping; Gu, Lijun; Li, Hui; Wang, Chen; Cao, Bin

doi:10.1093/infdis/jiy115

Cited by 80 publications

(102 citation statements)

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“…In severe influenza virus infection, prolonged viral shedding was associated with fatal outcome and delayed antiviral treatment was an independent risk factor for prolonged virus detection. 36 Similarly, effective antiviral treatment might improve outcomes in COVID-19, although we did not observe shortening of viral shedding duration after lopinavir/ritonavir treatment in the current study. Ran domised clinical trials for lopinavir/ ritonavir (ChiCTR2000029308) and intravenous remdesivir (NCT04257656, NCT04252664) in treatment of COVID-19 are currently in progress.…”

Section: Discussioncontrasting

confidence: 63%

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

et al. 2020

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Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. MethodsIn this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratoryconfirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 µg/mL (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 µg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.

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Section: Discussioncontrasting

confidence: 63%

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

et al. 2020

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“…Several observational studies have reported that corticosteroid therapy was linked to persistent viral RNA shedding in patients with avian influenza A (H7N9), MERS, and SARS [23][24][25]. Corticosteroid usage was related to prolonged viral RNA shedding time in this report as well, as patients with early RNA clearance had lower proportion of patients using corticosteroid compared with patients with late RNA clearance (40.5% vs 64.5%, P = .025).…”

Section: Discussionsupporting

confidence: 53%

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19)

Chen

Yuan

et al. 2020

Clinical Infectious Diseases

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Background. An outbreak of coronavirus disease 2019 is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding.Methods. In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan.Results. The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI,.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding.Conclusions. Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

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“…Multiple studies have reported that corticosteroid treatment is associated with prolonged influenza viral shedding in hospitalized patients [117][118][119], including in sporadic human infections with avian influenza A(H7N9) virus in China [120], and increased rates of secondary bacterial and fungal co-infections [121,122], which may lead to adverse clinical outcomes. However, there is some evidence to suggest that the increased risk attributed to corticosteroid treatment is a result of bias in observational studies.…”

Section: Treatment Of Influenzamentioning

confidence: 99%

Influenza virus-related critical illness: prevention, diagnosis, treatment

2019

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Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses. Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit. Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients. Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock. A number of pharmaceutical agents are in development for treatment of severe influenza.

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Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection

Abstract: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Cited by 80 publications

References 40 publications

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

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 RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19)

Influenza virus-related critical illness: prevention, diagnosis, treatment

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