key: cord-1005218-4dj97gw4 authors: Ueno, Akitoshi; Kawasuji, Hitoshi; Miyajima, Yuki; Fukui, Yasutaka; Sakamaki, Ippei; Saito, Mayuko; Yamashiro, Seiji; Morinaga, Yoshitomo; Oishi, Kazunori; Yamamoto, Yoshihiro title: Prolonged viral clearance of severe acute respiratory syndrome coronavirus 2 in the older aged population date: 2021-03-11 journal: J Infect Chemother DOI: 10.1016/j.jiac.2021.03.007 sha: 94c5e205e49bf72f1f6781eb8e9fa1796744caca doc_id: 1005218 cord_uid: 4dj97gw4 Introduction The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) is the standard method for the diagnosis of coronavirus disease 2019 (COVID-19). This PCR test can be positive even in patients who have recovered from the disease, and the duration for achieving viral clearance has not been clarified yet. Methods This study was conducted between April 3, 2020, and June 17, 2020, at the Toyama University Hospital and the Toyama Rehabilitation Home. We collected the data of patients with COVID-19, analyzing the duration until twice-consecutive negative qRT-PCR test. Results A total of 42 patients were enrolled. The median duration of the twice-consecutive negative qRT-PCR test was 29.0 d (interquartile range: 25.75–35.25). The longest duration of viral shedding was 73 d. The duration of viral clearance was significantly longer in the older (>65 years) group than in the younger group (34.5 d vs. 25.0 d, P <0.0001). Conclusion This study demonstrated that viral clearance tends to be sustained in the older adults. syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China, in December 2019 [1] . It has dramatically spread worldwide in 2020. The detection of SARS-CoV-2 by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) testing of respiratory specimens has been used for diagnosis [2] . However, qRT-PCR tests may continue being positive even after patients are cured of COVID-19. Although a negative qRT-PCR test has been the condition for permission to discharge patients hospitalized due to COVID-19, data on viral clearance in patients recovering from the disease are limited. We carried out a retrospective study to identify the role of viral clearance in the hospitalized population by measuring the qRT-PCR-positive duration. All patients were hospitalized either at the Toyama University Hospital, which is a 612-bed tertiary hospital in Toyama city, Toyama, Japan, or at the Toyama Rehabilitation Home, which is a 79-bed nursing home located in central Toyama city, Toyama, Japan. They were diagnosed with COVID-19 through qRT-PCR between April 3, 2020, and June 17, 2020. All samples were taken from the nasopharynx using swabs and sent to the Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, or the Toyama Institute of Health for qRT-PCR assays. The data collected from the medical records included age, sex, disease severity, medication, outcome, and the duration from presenting symptoms to twice-consecutive negative qRT-PCR test. Disease severity classified mild, moderate, and severe. Mild group did not receive supplemental oxygen therapy, and moderate group received supplemental oxygen therapy. Severe group received mechanical ventilation or extracorporeal membrane oxygenation. Continuous variables were represented as the J o u r n a l P r e -p r o o f mean and standard deviation (SD) or as the median and interquartile range (IQR). Continuous data were analyzed using the Wilcoxon rank-sum test. The threshold for statistical significance was set at P<0.05. qRT-PCR may also detect non-infectious fragments of the viral RNA. Singanayagam et al. reported that culture-positive virus was hardly detected within 10 d after symptom onset [3] . Therefore, it is recommended by World Health Organization that symptomatic patients are released from isolation 10 d after symptom onset, plus at least an additional 3 J o u r n a l P r e -p r o o f d without symptoms. [4] . In Japan, discharge criteria for symptomatic patients are after 10 d symptom onset and 72 h from symptom resolution, or negative two PCR tests at intervals of at least 24 h after 24 h of symptom resolution [5] . At the time of admission, two consecutive negative PCR tests, at least 24 h apart, were required to discharge the patient. As we found in our study, older aged patients can be PCR-positive even after healing. In some patients older than 80 years, it took more than 40 d to become negative PCR tests. These patients were not immunocompromised status but needed assistance for daily living and had diseases related aging such as dementia, In addition, some rehabilitation facilities or nursing home require the result of negative-PCR test at the time of transfer, even though the patient meets the criteria for discharge, which inhibits the recovery of COVID-19 patients and interferes with their quality of life because they cannot be rehabilitated or moved to a facility where they are accustomed to living. We suggest complying with the criteria for discharge regardless of the PCR results in patients recovered from COVID-19. 3) Figure 1 このグラフを見ると、80 At the time of admission, two consecutive negative PCR tests, at least 24 h apart, were required to discharge the patient. As we found in our study, older aged patients can be PCR-positive even after healing. In some patients older than 80 years, it took more than 40 d to become negative PCR tests. These patients were not immunocompromised status but needed assistance for daily living and had diseases related aging such as dementia, hypertension, and osteoporosis. The relationship between virus detection by PCR and infectivity is not entirely clear. qRT-PCR may also detect non-infectious fragments of the viral RNA. Singanayagam et al. reported that culture-positive virus was hardly detected within 10 d after symptom onset [3] . Therefore, it is recommended by World Health Organization that symptomatic patients are released from isolation 10 d after symptom onset, plus at least an additional 3 d without symptoms. [4] . In Japan, discharge criteria for symptomatic patients are after A novel coronavirus from patients with pneumonia in China Diagnostic testing for SARS-CoV-2 Interim guidance Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19 World Health Organization. Criteria for releasing COVID-19 patients from isolation Scientific Older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples Adaptive Immunity to SRS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity A novel coronavirus from patients with pneumonia in China Diagnostic testing for SARS-CoV-2 Interim guidance Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19 World Health Organization. Criteria for releasing COVID-19 patients from isolation Scientific Japanese Ministry of Health, Labor and Welfare. Revision of discharge and release criteria Older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples We would like to thank all the hospital staff supporting this study. This study was supported by the Research Program on Emerging and Re-emerging Infectious Diseases from AMED Grant No. JP20he0622035. The authors declare no conflicts of interest. This study was approved by the Ethics Committee of the Toyama University Hospital