key: cord-1026928-ja8xggnd
authors: Nakagawara, Kensuke; Masaki, Katsunori; Uwamino, Yoshifumi; Kabata, Hiroki; Uchida, Sho; Uno, Shunsuke; Asakura, Takanori; Funakoshi, Takeru; Kanzaki, Sho; Ishii, Makoto; Hasegawa, Naoki; Fukunaga, Koichi
title: Acute Onset Olfactory/Taste Disorders are Associated with a High Viral Burden in Mild or Asymptomatic SARS-CoV-2 Infections
date: 2020-07-26
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.07.034
sha: c5134aa7f33b069ee8a1cf6df16e54442f1ac382
doc_id: 1026928
cord_uid: ja8xggnd

We investigated the association between symptoms and viral clearance in 57 patients with asymptomatic/mild SARS-CoV-2 infection using cycle threshold (Ct) qPCR values. Patients with olfactory/taste disorders (OTDs) exhibited lower qPCR Ct values and longer time to negative qPCR than those without OTDs, suggesting association between OTDs and high viral burden.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread globally. In Tokyo, Japan, the total number of confirmed cases has been increasing, particularly from March to April 2020. Real-time polymerase chain reaction (qPCR) using clinical specimens such as nasopharyngeal swabs or sputum is the standard of reference for diagnosis, and recent studies have shown an association between qPCR cycle threshold (Ct) values and disease severity (1, 2) . Specifically, Ct values from qPCR tests conducted on nasopharyngeal or sputum specimens of patients on admission were negatively associated with disease severity and progression to severe illness, and mild patients showed an early viral clearance using Ct values (1, 2) . However, little is known about the association between symptoms and viral clearance. Our study investigated this association in mild/asymptomatic cases using qPCR Ct values of nasopharyngeal swab samples.

Fifty-seven patients with asymptomatic/mild SARS-CoV-2 infection (without pneumonia or any organ failure), who were admitted to Keio University Hospital for isolation and/or treatment from March 28 to April 23, 2020, were included in this study. All patients had no symptoms of dyspnea and, no findings of pneumonia on chest x-ray on admission. They were diagnosed with SARS-CoV-2 infection using qPCR conducted upon admission and did not receive any antiviral treatments. Pre-admission symptoms were collected at admission, and after admission, patients were prospectively checked daily by physicians for symptoms, such as fever, sore throat, nasal drip/congestion, cough/sputum, olfactory and taste disorders (OTDs), headache, fatigue, joint pain, and diarrhea. qPCR was performed on all nasopharyngeal swab samples using the SARS-CoV-2 CDC assay protocol and Ct values were reported for two genetic markers, the N1 and N2 viral nucleocapsid protein gene regions J o u r n a l P r e -p r o o f (3) . A value of 45 cycles or less indicates a positive result for SARS-CoV-2. qPCR testing was repeated every 3-7 days until the results were negative. We retrospectively assessed the association between symptoms and Ct values or the period to negative qPCR.

The clinical characteristics and symptoms of the patients are shown in Appendix 1. The mean age was 35.4 years and 25 patients (43.9%) were males. Thirty-four patients (59.6%) had comorbidities (all under control). The most common disease was neoplasia (12.3%), followed by asthma (8.8%), and psychiatric disorders (7.0%). Twenty-eight patients (49.1%) were asymptomatic, with common symptoms on clinical courses being fever (15; 26.3%), sore throat (11; 19.3%), acute onset OTDs (10; 17.5%), headache (7; 12.3%), cough/sputum (8; 14.0%), and nasal drip/congestion (4; 7.0%). Figure 1 shows the prevalence of each symptom over time. Fever, sore throat, and nasal drip congestion were relatively early and prolonged for about one week. The median duration of fever was 3 days (interquartile range: Our results showed that patients with asymptomatic or mild SARS-CoV-2 infection with a higher viral load required a longer time to exhibit negative qPCR results, suggesting that Ct values reflect viral load in principle (4) . Moreover, our results demonstrated that fever and OTDs were significantly associated with a higher viral burden and longer time to negative qPCR. Compared with fever, data on OTDs are less available unless intentionally assessed, even though OTDs are a common symptom in SARS-CoV-2 infection (5-7). immune genes. Nat Med 2020;26:681-7. https://doi.org/10.1038/s41591-020-0868-6.

Hou 

Viral dynamics in mild and severe cases of COVID-19

SARS-CoV-2 viral load in sputum correlates with risk of COVID-19 progression

Centers for Disease Control and Prevention. 2019-novel coronavirus (2019nCoV) real-time rRT-PCR panel primers and probes

CoV-2 infections and transmission in a skilled nursing facility

Olfactory dysfunction: a highly prevalent symptom of COVID-19 with public health significance

Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study

Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study

CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate