key: cord-258315-yt1ytasw
authors: Kato, Hideaki; Shimizu, Hiroyuki; Shibue, Yasushi; Hosoda, Tomohiro; Iwabuchi, Keisuke; Nagamine, Kotaro; Saito, Hiroki; Sawada, Reimin; Oishi, Takayuki; Tsukiji, Jun; Fujita, Hiroyuki; Furuya, Ryosuke; Masuda, Makoto; Akasaka, Osamu; Ikeda, Yu; Sakamoto, Mitsuo; Sakai, Kazuya; Uchiyama, Munehito; Watanabe, Hiroki; Yamaguchi, Nobuhiro; Higa, Ryoko; Sasaki, Akiko; Tanaka, Katsuaki; Toyoda, Yukitoshi; Hamanaka, Shinsuke; Miyazawa, Naoki; Shimizu, Atsuko; Fukase, Fumie; Iwai, Shunsuke; Komase, Yuko; Kawasaki, Tsutomu; Nagata, Isao; Nakayama, Yusuke; Takei, Tetsuhiro; Kimura, Katsuo; Kunisaki, Reiko; Kudo, Makoto; Takeuchi, Ichiro; Nakajima, Hideaki
title: Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship
date: 2020-05-13
journal: J Infect Chemother
DOI: 10.1016/j.jiac.2020.05.005
sha: 
doc_id: 258315
cord_uid: yt1ytasw

Abstract We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

Keywords: coronavirus; SARS-CoV-2; outbreak; COVID-19; Diamond Princess cruise ship A novel coronavirus disease (COVID-19) caused by SARS-CoV-2 in early 2020 abruptly spread within three months from the east-Asian countries to other parts of the world.

In Japan, the first outbreak of COVID-19 was reported in a giant cruise ship called the Diamond Princess. This cruise ship had a gross tonnage of 115,000 tons with a maximum capacity of 2706 passengers and 1100 operating staffs. The cruise started on January 20, 2020, from Yokohama stopped at Kagoshima (Southern Japan), Hong Kong, Da Nan and Chan May who were confirmed or suspected to be infected with SARS-CoV-2 were kept isolated on the cruise ship, and they were allowed to disembark from the cruise ship only after the quarantine observation for two weeks. Disembark of 3711 individuals on the cruise ship was completed on March 1. Meanwhile, individuals who required medical care, mainly those with severe symptoms during February 3 and March 1, were transferred to local hospitals near the Yokohama city area, which is the largest city in the Kanagawa Prefecture for medical care [3] .

In this study, we describe the clinical conditions, treatment, and the clinical course of the patients positive for SARS-CoV-2 who were transferred from the Diamond Princess cruise ship for further medical care to the participating hospitals in this study.

The patients' vital signs, laboratory data, chest radiographs, or computed tomography (CT) findings at the time of admission and treatment, and the data on the clinical course and prognosis were collected using case report forms. Case report forms were collected on March 11 and March 19, 2020. The clinical findings of the patients without pneumonia were compared with those of the patients with pneumonia. The patient race was determined based on the estimation of his/her ancestor by each participating physician. Patient severity was defined according to World Health Organization criteria [4] . No patient was excluded because of bacterial or any other type of viral pneumonia by additional laboratory tests and sputum culture. Table 2 . Ceftriaxone and azithromycin were mostly chosen as the antibiotics for the initial treatment. With regard to the anti-viral drugs, the following neuraminidase inhibitors were administered in 14 patients: oseltamivir (n = 6), peramivir (n = 4), baloxavir (n = 1), and a combination of oseltamivir and baloxavir (n = 3). LPV/r was administered to 24 patients. Two patients with pneumonia were treated with a combination of neuraminidase inhibitors, LPV/r, and ribavirin. In addition, ciclesonide inhalation, which was suggested to have anti-coronavirus activity, was administered in 8 patients with pneumonia. Notably, the severity of this disease in the patients transferred from the cruise ship was very high compared with that previously reported in the general population in China [5, 6] .

The one reason was attributed to advanced age [6] . Generally, the average age of the Japanese passengers on Asian cruise ships is reported to be 57 years [7] . Most of the individuals on the Diamond Princess on February 5, 2020, were aged ≥60 years of age [2] . The crowded and closed environment on the cruise ship was possibly a suitable condition for high transmission of respiratory infections [8] . In these individuals with COVID-19, the severity of the disease varied widely from almost asymptomatic to critical cases such as those requiring ventilator support. The initial symptoms -fever, dry cough and general fatigue, were quite nonspecific.

The severity of the disease depended on the presence of pneumonia. The findings of our study show that it is critical to differentiate patients with pneumonia from those without pneumonia to predict their clinical course and treatment plan. High LDH and AST levels possibly reflect the interstitial lung inflammation due to COVID-19. Low lymphocyte count and high LDH level were considered key to predict pneumonia in patients with COVID-19 because their levels serve as predictors of severe conditions [9] . The bilateral GGOs was helpful for diagnosing COVID-19. Chest CT is more sensitive than chest radiographs, and the bilateral GGOs in the lower lung lobes are reported to be specific to COVID-19 [10, 11] . We suggest that chest CT should be considered if a patient is suspected to have pneumonia due to COVID-19 but PCR findings were still under examination. No treatment regimen has yet been established for the treatment of COVID-19. In the participating hospitals, unapproved drugs were used for the treatment. Treatment with LPV/r, neuraminidase inhibitors, ciclesonide inhalation, favipiravir and rivabirin were attempted. Our colleagues reported that ciclesonide inhalation is effective for the treatment of COVID-19 [13, 14] .

Our study has several limitations. First, data were collected from the case report forms from each attending physician in the participating hospitals. The diagnosis and treatment were depended on the clinical decision of each physician. Second, this study was descriptive and we did not properly evaluate the efficacies of the drugs or the supportive care. Further studies should be performed to assess the efficacy of these drugs for the treatment of severe cases of COVID-19. Third, we were not able to investigate all cases of COVID-19 on the Diamond Princess cruise. The environment inside the cruise ship is suitable for high transmission of respiratory infections [8] . Because individuals with severe conditions during an outbreak are possibly transferred to nearby local hospitals, managing patients during an outbreak is a big challenge to local medical systems. We believe that our findings of patients with COVID-19 during its outbreak on a cruise ship can help to manage a large number of patients infected within a short period of time. Assessment of disease severity was crucial to manage a large number of patients.

We did not receive any funding support for this study. 

Institute of Infectious Diseases. Field Briefing: Diamond Princess

COVID-19 First Stage in Japan -How we treat Diamond Princess Cruise Ship with 3700 passengers?

Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected

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

Clinical characteristics of coronavirus disease 2019 in China

Cruise Lines International Association

COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia

Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings

A case of coronavirus disease 2019 treated with ciclesonide

Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases

Lymphocyte count (/µL) 1071

We thank our medical staffs and colleagues who were involved in caring for the patients from the cruise ship. We sincerely appreciate our families for supporting our jobs. We also appreciate the municipal officers of the Yokohama City and the Kanagawa Prefecture for cooperating with us in managing the patients. The authors would like to thank Enago (www.enago.jp) for the English language review.

The authors have no conflict of interest to declare.

This study was approved by the ethics committee at each participating institution.