key: cord-0898173-k44ezby2
authors: Ishii, Makoto; Terai, Hideki; Kabata, Hiroki; Masaki, Katsunori; Chubachi, Shotaro; Tateno, Hiroki; Nakamura, Morio; Nishio, Kazumi; Koh, Hidefumi; Watanabe, Risa; Ueda, Soichiro; Terashima, Takeshi; Suzuki, Yusuke; Yagi, Kazuma; Miyao, Naoki; Minematsu, Naoto; Inoue, Takashi; Nakachi, Ichiro; Namkoong, Ho; Okamori, Satoshi; Ikemura, Shinnosuke; Kamata, Hirofumi; Yasuda, Hiroyuki; Kawada, Ichiro; Hasegawa, Naoki; Fukunaga, Koichi
title: Clinical characteristics of 345 patients with coronavirus disease 2019 in Japan: A multicenter retrospective study
date: 2020-09-10
journal: J Infect
DOI: 10.1016/j.jinf.2020.08.052
sha: 38c5feda8010480b6900f9a12fecb72a823f6eec
doc_id: 898173
cord_uid: k44ezby2

nan

Keywords: COVID-19, SARS-CoV-2, risk factors, retrospective study, Japan was first reported in Wuhan, China, in December 2019 and subsequently spread globally, leading to a pandemic; 2 as of August 25, 2020, more than 23 million people worldwide had been confirmed to have COVID-19 infections, and more than 810,000 patients had died. 3 Although approximately 80% of COVID-19 cases are classified as mild or asymptomatic, 15% of adults infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) developed severe illness and required oxygen supplementation, and an additional 5% progressed to a critical state. 2 An increasing number of literature indicated the specific risk factors for the progression of severe illness and poor outcomes resulting from COVID-19. 1 For example, a recent large-scale study demonstrated that older age and certain clinical conditions (diabetes, respiratory diseases, and heart, kidney, and autoimmune conditions) are risk factors for death from COVID-19. 4 Although there is a limited number of effective therapies to date, the identification of risk factors for disease progression and clinical outcomes is crucial, because it means appropriate care and the proper allocation of medical resources can be timely provided.

Japan is characterized by a rapidly aging population, with the highest proportion (28.4%) of elderly citizens (65 years and older) worldwide. 5 In Japan, the first case of COVID-19 was reported in mid-January 2020. The first outbreak in Japan occurred on the Diamond Princess cruise ship in February 2020. Since then, the number of COVID-19 patients has increased exponentially. A state of emergency was declared in Tokyo on April 7 and was subsequently lifted on May 25, 2020, due to the decreased number of newly diagnosed COVID-19 cases. Subsequently, the number of COVID-19 cases quickly increased again; more than 63,000 people had been diagnosed with COVID-19, and more than 1,200 people had died of COVID-19 in Japan as of August 25, 2020. 3 A few studies have shown the clinical features or the risk factors for the progression of severe illness and death, in a large number of COVID-19 patients in Japan affected by community transmission, other than the Diamond Princess cruise ship. [6] [7] [8] For this retrospective multicenter study, we evaluated the characteristics and prognostic factors of 345 patients with COVID-19, who were admitted to either Keio University Hospital or one of 13 community hospitals located in the Greater Tokyo Area from February 1 to June 19, 2020, to investigate the similarity in these risk factors to those previously reported in an aging country such as Japan. All patients were followed up until June 19, 2020 in the hospital or were discharged before June 19.

The median age of these patients was 54 years; 198 (57.4%) of the patients were male, and 327 (94.8%) were Japanese (Table 1) . Additionally, 167 (48%) had at least one comorbidity, and 17 (6.1%) were obese (defined as a BMI (body mass index) of ≥30 kg/m 2 ). Among various comorbidities, hypertension was the most common (26.1%), followed by diabetes (13.9%) and hyperuricemia (8.1%). The median duration of illness before diagnosis was 5 days. The most common symptoms reported during the observation period were fever (3.0%), followed by cough (48.3%), which were consistent with previous report. 2 Next, we compared the severe (those who required oxygen supplementation) and non-severe patient groups as well as the living and deceased groups. The number of patients with COVID-19 who required oxygen supplementation was 112 (32.5%), and the number of patients who died in the hospital was 23 (6.7%) ( Table 1 ).

The risk factors that increased the need for oxygen supplementation were older age, male sex, history of smoking, various comorbidities (hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease [COPD], hyperuricemia, and chronic kidney disease), and specific disease symptoms (consciousness disorder, fever, shortness of breath, nausea/vomiting, and general fatigue) (Table 1) . Table 1 shows the positive risk factors for COVID-19-related death. We performed univariate analysis of risk factors for severe illness in patients with COVID-19 (not shown). Older age, male sex, a history of smoking, comorbidities (hypertension, diabetes, cardiovascular disease, COPD, hyperuricemia, and chronic kidney disease), and specific disease symptoms (consciousness disorder, fever, shortness of breath, nausea/vomiting, and general fatigue) were positively associated with the need for oxygen supplementation. Subsequently, we performed multivariate analysis of risk factors affecting the need for oxygen supplementation in COVID-19 patients ( Univariate analysis of risk factors for death resulting from COVID-19 was performed (not shown). Older age, comorbidities (diabetes, cardiovascular disease, COPD, hyperuricemia, chronic liver disease, and chronic kidney disease), and specific symptoms (consciousness disorder and shortness of breath) were associated with death resulting from COVID-19. We further performed multivariate analysis of risk factors for death associated with SARS-CoV-2 infection (Table 2) , and factors, including chronic kidney disease (OR 5.74), older age (OR 5.43), and hyperuricemia (OR 3.60), were independently associated with death resulting from COVID-19.

Our results demonstrate that chronic kidney disease (CKD), followed by older age and hyperuricemia, are the most common independent risk factors for COVID-19-related death in this study ( Table 2 ). CKD and older age have been previously reported as risk factors for in-hospital death; 4 this is consistent with our data. However, preexisting hyperuricemia has not been previously reported as a risk factor for death resulting from COVID-19; to our knowledge, this is the first study demonstrating that hyperuricemia is an independent risk factor for death in COVID-19 patients.

Hyperuricemia is a well-established risk factor for diabetes and CKD; 9 however, the mechanism underlying the relationship between hyperuricemia and COVID-19-related mortality is unclear. As inflammation and oxidative stress (key status in COVID-19 patients) have been reported as potential causes of higher mortality risks associated with hyperuricemia, 10 the inflammation and oxidative stress induced by SARS-CoV-2 infections likely contributed to this process.

In conclusion, we have shown the real-world clinical characteristics and risk factors for COVID-19 in the Greater Tokyo Area. Hyperuricemia is a novel risk factor for COVID-related death.

Pandemic Crisis Research Grant (to M.I.).

None. 

A comparison of mortality-related risk factors of COVID-19, SARS, and MERS: A systematic review and meta-analysis

Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

Johns Hopkins Coronavirus Resource Centre

OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Elderly citizens accounted for record 28.4% of Japan's population in 2018, data show

Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis

Natural History of Asymptomatic SARS-CoV-2 Infection

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship

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Approximate Mortality Risks between Hyperuricemia and Diabetes in the United States