key: cord-293997-4wjf1znf
authors: Asai, Nobuhiro; Sakanashi, Daisuke; Nakamura, Akiko; Kishino, Takaaki; Kato, Hideo; Hagihara, Mao; Shiota, Arufumi; Koizumi, Yusuke; Yamagishi, Yuka; Mikamo, Hiroshige
title: Clinical manifestations and radiological features by chest computed tomographic findings of a novel coronavirus disease-19 pneumonia among 92 Japanese people
date: 2020-08-20
journal: J Microbiol Immunol Infect
DOI: 10.1016/j.jmii.2020.07.011
sha: 
doc_id: 293997
cord_uid: 4wjf1znf

Abstract Introduction The novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12-45% among cases who required intensive care unit admission. COVID-19 pneumonia Patients and methods For the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings. Results A total of 92 patients were enrolled in this study. The median age was 66 years (range 16-92 years). For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%). Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three (47%) had no respiratory symptoms. As for radiological findings by chest CT scan, ground-glass opacities (GGO)s, peripheral distribution, bilateral lung involvements were seen in 88 (96%), 76 (83%) and 78 (85%), respectively. Conclusion It is difficult to diagnose as COVID-19 pneumonia due to poor respiratory symptoms. Chest CT findings typically show GGO, peripheral and bilateral shadows. Patients should have chest CT performed if suspected for early diagnosis and therapeutic intervention, resulting in a favorable outcome and prevention of secondary nosocomial transmitted infection.

The novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12-45% among cases who required intensive care unit admission.

For the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings.

A total of 92 patients were enrolled in this study. The median age was 66 years (range 16-92 years).

For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%).

Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three J o u r n a l P r e -p r o o f 

We present 8 COVID-19 pneumonia cases ( Table 1) 

A total of 92 patients from 55 case reports were enrolled in this study. Table 1 shows patients' characteristics and clinical outcomes. The patients were 50 males (54%) and 42 females (46%).

The median age was 66 years (16-92 years). Twenty-eight patients (30%) had a close contact with someone with COVID-19. There were no obvious history of exposure in 21 (23%).

The most frequent underlying diseases was hypertension in 32 (36%), followed by diabetes mellitus in 18 (20%). As for clinical symptoms, fever was seen the most frequently in 66 (72%), followed by cough in 37 (40%), general fatigue in 33 (36%). Radiological findings were shown in Table 2 . Ground-glass opacities (GGO)s and mixed lesions with GGOs and lobular shadows were seen in 88 (96%) and 27 (29%), respectively. Neither mass shadows nor tree-in-bud appearances were seen in all patients. The predominant pattern observed was bilateral in 78 (85%), unilateral lung involvements in 14 (15%) and peripheral distribution in 76 (83%). Patchy shadows were found more frequently in 20 to 39 year old-patients than in others (≧40 years) (50% vs. 8%, p=0.008 by Fisher's exact test). The mean timing for CT scan after the onset of signs and symptoms was 6.1 days. There was no correlation between the timing after the onset and any radiological features. There was no difference of timing of CT scan between bilateral and unilateral findings (6.1 vs. 6.1 days, p=0.956). We could not find any correlation between the underlying diseases and the radiological features. As for the correlation between the radiological featuress and the outcomes, a diffuse pattern is more frequently seen in the death group than in the survival group even though there was no statistical difference (100% vs. 56%, p=0.082). There was no correlation between other patterns and the outcomes (data not shown).

As for the initial treatment, lopinavir/ritonavir was used the most frequently in 28 (34%), followed by ciclesonid in 26 (32%). Favipiravir was prescribed in 18 (22%). Combination therapy with 2 more agents and no therapy were seen in 45/81 (56%) and 14/82 (17%), respectively. In terms of outcomes, 14 patients (17%) required mechanical ventilations, 61/65 (94%) were survived and 4/65 (6%) died. Twenty-eight patients moved to another institute or under treatment.

Typical tomographic findings of COVID-19 pneumonia are GGOs, peripheral distribution and bilateral lung involvements 6,7 as same as the result of our study. Notably, respiratory symptoms such as cough and sputum were seen in 36 (39%) and 4 (4%) respectively among the patients with COVID-19 pneumonia. Forty-three patients (47%) had no respiratory symptoms such as cough, sore throat, runny nose or dyspnea. This could be explained by that the clinical J o u r n a l P r e -p r o o f course of COVID-19 pneumonia would progress slowly in many cases, even if some cases have acute respiratory failure. Although all of coronavirus infections could cause cytokine storm, some reported that the pathophysiology of MERS and SARS-CoV differ from that of COVID-19. 8 The disease severity could depend on the correlation between the host immunity and the imbalance of helper T-cell 1 and 2. Therefore, it is reasonable that some pneumonia patients improved without any therapy. 1,2 Some COVID-19 cases which were considered as light or moderate, unfortunately died. We worry that some COVID-19 patients who were misdiagnosed as not having pneumonia could develop acute respiratory failure, or cytokine release syndrome (CRS), resulting in unexpected) deaths. Different shadows could appear in different patients depending on the age and conditions. Immunological effect could be influenced differ in patients' ages and conditions. Some documented that predominant shadows in the right of the lung were seen among the patients.

We could not find correlation between disease severity and the predominance of the lung side due to a lack of tomographic information. 6 The patients in this review were older and have more comorbidities than those in previous studies. 6, 8 In this review, all patients who died were older than 75 years. Three of the patients had severe comorbidities (One had no information of underlying disease). We recommend that Fortunately, the mortality rate of COVID-19 in Japan is the lowest all over the world. 9 This result may be attributable to the specific aspects in the Japanese healthcare system. Japanese medical service is based on a free-access policy and medical cost could be covered by a universal public insurance system for every citizen as well as for inhabitants from abroad. Thus, it is easier to perform CT scan in Japan than any other country. We believe that early diagnosis of COVID-19 pneumonia could contribute to a favor outcome. In order to reduce the risk of nosocomial infection and mortality of the disease, chest CT should be performed even though we are facing the escalation of medical costs and staff's labors.

There are some limitations in our study. First, this is a retrospective study in a small population. Second, this study was a case review of the literature in which clinical information might be insufficient. Third, this review has included only cases who showed positive SARD-CoV2-RT-PCR testing. Thus, these patients might not reflect the whole patients with COVID-19 pneumonia in the real world.

We concluded that COVID-19 pneumonia patients show typically GGO, peripheral, bilateral CT, computed tomography; GGO, ground-glass opacity; SD, standard deviation.

＊ Timing CT scan after onset of the symptoms and signs were analyzed in 84 patients due to missing information.

There was no correlation between the date after onset and any tomographic features. We could not find the correlation between underlying disease and tomographic features.

As for the correlation between radiological features and outcome, diffuse pattern is more frequently seen in death group than survival group even though there was no statistical difference (100% v.s. 56%, p=0.082). Other patterns of CT scan J o u r n a l P r e -p r o o f

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

Report of the WHO-China Joint Mission on Coronavirus Disease

Phylogenetic network analysis of SARS-CoV-2 genomes

The Japanese Association for Infectious Diseases

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

World Health Organization. Coronavirus disease (COVID-19) Pandemic

We are grateful for the diligent and thorough critical reading of our manuscript by Dr. YoshihiroOhkuni, Chief Physician, Taiyo and Mr. John Wocher, Advisor, Kameda Medical Center (Japan). We also thank all the physicians, nurses and medical staffs who cared these patients in Aichi Medical University hospital.

All co-authors have none declared.J o u r n a l P r e -p r o o f