In patients with COVID-19, age over 50 years is also considered as an indication for antiviral drug therapy, in addition to hypoxemia. At this time, it still remains unclear as to which clinical markers can be considered as being predictive of severe COVID-19 pneumonia with hypoxemia. We categorized 49 patients with COVID-19 pneumonia into the following 4 groups by the clinical manifestations : stage A : no symptoms, and no viral pneumonia on chest computed tomography (CT) ; stage B : symptom (s) present, but no viral pneumonia on CT ; stage C : viral pneumonia on CT, but no hypoxemia ; stage D : viral pneumonia on CT, with hypoxemia. The clinical background characteristics that were correlated with the disease severity were the patient age, presence/absence of complications, smoking history, and presence/absence of fever and diarrhea, but multivariate analysis identified only smoking history as being significantly predictive of stage D disease. The lymphocyte count, serum CRP level, serum ferritin level and incidence of consolidation on CT were significantly different between patients with stage C and stage D disease. Therefore, we propose five predictors of severe COVID-19 pneumonia, namely, smoking history, lymphocyte count ≦1,200 μL,serum ferritin ≧400ng/mL, serum CRP ≧2.5mg/dL, and presence of consolidation on CT. The interval (in days) from the onset of symptom (s) to the first negative result of PCR for SARS-CoV2 was well correlated with the number of these risk factors in each patient (p＜0.0001）.

The outbreak of the novel coronavirus infection in Wuhan City, Hubei Province, China, in December 2019, has spread rapidly around the world, and the number of cases with no apparent route of transmission (cases of community transmission) is increasing in Japan. We have encountered 45 cases of COVID-19 infection, including 33 male and 12 female patients. The average age of the patients was 50.6 years. The symptoms were fever in 39 (86.7%) cases, cough in 33 (73.3%) cases, malaise in 24 (53.3%) cases, and diarrhea in 5 (11.1%) cases. In addition, according to the Kanagawa-model severity classification constructed by Kanagawa Prefecture to avoid collapse of the medical infrastructure caused by a sudden increase in patients, 30 cases were classified as having mild disease, 14 as having moderately severe disease, and 1 as having severe disease. Of the 30 patients with mild disease, 1 (3.3%) showed deterioration to moderately severe disease during the clinical course, and of the 14 patients with moderately severe disease, 6 (42.9%) showed deterioration to severe disease. The findings in respect of the subsequent clinical course of the patients suggest that the Kanagawa-model severity classification is a reasonable classification for satisfactory triage of patients.

An immunochromatographic assay that has been developed for the detection of antibodies in bloodderived specimens is raising expectations for the diagnosis of COVID-19, the disease caused by the novel corona virus SARS-CoV-2. Herein, we studied the interval from symptom onset to the first positive results of the immunochromatographic assay for IgM and IgG antibodies in 52 patients with a definitive diagnosis of COVID-19 (disease confirmed by the PCR test). Furthermore, we also examined the test results in 35 patients with acute fever and pneumonia who were negative by the PCR test.
All patients with a definitive diagnosis of COVID-19 were confirmed to be antibody-positive. The mean time from symptom onset to the first positive result for IgM antibody was 11.9 days (minimum : 5, median :11), and that to the first positive result for IgG antibody was 11.2 days (minimum : 5, median : 11). No significant difference was observed between the tests for IgM and IgG antibodies in terms of the percentage of positive patients or the interval from first onset to the first positive test result. There were no patients in whom the test for IgM became positive before the test for IgG. In 45 patients (87%), both IgM and IgG became positive at the same time, and in the remaining 7 patients (13%), the test for IgG became positive before that for IgM.
Of 35 patients with acute fever and pneumonia who tested negative by the PCR test for SARS-CoV-2,not COVID-19, 6 (17.1%) and 1 (2.8%) showed positive results for anti-IgG antibody and anti-IgM antibody, respectively.
Our study results were quite limited, and we do not intend to conduct a performance evaluation of the reagents contained in the detection kits. Assessment of antibody detection reagents for the immunochromatographic assay, which can be used as a complementary test to PCR, is expected in the future ; however,the findings should be reviewed carefully.

The number of the patients with coronavirus disease 2019 (COVID-19) is increasing, and shortage of hospital beds for these patients is a cause for serious concern. Here, we report the clinical course of 11 patients who were admitted to our hospital with COVID-19 that developed during their quarantine period in a large cruise ship, and discuss the factors associated with the disease severity and length of hospitalization.
The median age of the 11 patients was 62 years, and 36% were men. The disease severity was mild in 7 patients, moderate in 4 patients, and severe in none of the patients. The median time from symptom onset to disease remission was 13 days for patients with moderately severe disease, and 7 days for patients with mild disease. The median interval from symptom onset to confirmation of the first negative result of PCR was 16 days for patients with moderately severe disease, and 14 days for patients with mild disease. The median time from symptom onset to discharge was 22.5 days for patients with moderately severe disease cases, and 16 days for patients with mild disease. Some patients needed prolonged hospitalization because of persistently positive results of PCR even after remission of symptoms. Comparison between the patient groups with moderately severe disease and mild disease showed that the patients with moderately severe disease were older and had higher serum ferritin and serum amyloid protein (SAA) levels than the patients with mild disease.
Even in patients with mild to moderate COVID-19, two to three weeks were required from symptom onset to confirmation of the first negative result of PCR, and this was one of the major factors for prolonged hospitalization. The serum ferritin levels and SAA levels might be predictors of the disease severity.

Recently, cases of coronavirus disease 2019 (COVID-19) with unknown routes of transmission are being reported from various parts of Japan. When close contacts of infected patients present with symptoms, the index of suspicion for COVID-19 is high, and consultations and examinations are implemented with sufficient infection control measures in place. On the other hand, the possibility of COVID-19 is often difficult to consider initially in cases from the community presenting with upper respiratory tract symptoms, such as sore throat and cough, and/or fever. The initial upper respiratory tract symptoms are similar to those of common cold. It is only much later, usually about one week after the appearance of symptoms, that COVID-19 is suspected and the test for SARS-CovV-2 is performed. Until then, the patients may have consulted their family doctor and been tested for influenza, and may have been prescribed a cold medicine or antitussive. We encountered 10 cases of COVID-19 pneumonia that developed in the community and tested positive for SARS-CoV-2 by PCR. The presenting symptoms were a fever of over 38̊C in 9 cases, nasal discharge in 1 case, sore throat in 4 cases, cough in 8 cases, sputum in 5 cases, shortness of breath in 6 cases, malaise in 7 cases, and gastrointestinal symptoms in 3 cases. Five cases also showed poor health and fever in the family. All cases needed 1-3 consultations to be finally diagnosed, and the interval from the appearance of symptoms to diagnosis was 5-12 days. Coarse crackles could be auscultated in only one case, and the SpO₂ was more than 95% in 8 cases, and 80% in 2 cases. No increase of the peripheral white blood cell count was observed in any of the cases, and the blood lymphocyte count was less than 1,000/μL in 6 cases. The serum CRP showed only a slight increase to up to 5mg/dL in 7 cases, and a slight increase in the d-dimer level was observed in 5 cases. In some cases, while it was difficult to detect abnormalities on the chest X-ray,chest computed tomography showed multiple bilateral ground-glass opacities, predominantly in the peripheral/subpleural regions, in all cases. Nine of the 10 patients also showed lesions in the lower right lobe. We describe the clinical characteristics of COVID-19 pneumonia among cases of infectious diseases encountered in the community. Based on the above, we suggest that in cases from the community presenting with fever and upper respiratory symptoms, one clue to suspecting COVID-19 is the presence of persons among family members who are also unwell.

On April 5, 2020, guidelines for COVID-19 were issued that allowed asymptomatic carriers and mildly ill persons to remain at home. However, due to the unexpected increase in the number of symptomatic patients, many patients are now hospitalized. We accepted COVID-19 patients from the cruise ship, Diamond Princess. We focused on 6 cases with mild symptoms and evaluated the results of chest computed tomography (CT) and blood tests, the clinical course, the period until two consecutive negative test results of RT-PCR, and the length of hospitalization in these patients.

St. Lukeʼs International Hospital had been accepting a large number of patients with mild to severe COVID-19, before COVID-19 became a designated infectious disease on February 1, 2020. The first patient with COVID-19 admitted to our hospital was a man in his 40s from Wuhan, the second case of COVID-19 registered in Japan, and officially, the first case in a person of Chinese origin in Japan. The third patient, a Canadian man in his 60s who contracted the infection in the cruise ship, Diamond Princess, had very severe disease. However, his clinical symptoms improved and he was discharged from the hospital. In this paper,we discuss four cases of COVID-19.

We encountered two female patients with COVID-19 ―one transferred from the cruise ship, Diamond Princess, docked in the Yokohama port, and the other with community transmission of the infection. The former patient had asymptomatic pneumonia, which subsided spontaneously. The latter patient suffered from severe rapidly worsening pneumonia which necessitated mechanical ventilation and extracorporeal membrane oxygenation, but eventually showed complete resolution of the disease. Although the lung involvement in those two cases at their first evaluation seemed to be equal, they exhibited very different clinical courses ―one showing self-limiting asymptomatic pneumonia and the other showing severe progressive pneumonia.

The disease outbreak caused by the novel coronavirus, SARS-CoV-2, in December 2020 in Wuhan,China, has spread worldwide, threatening global health. While SARS-CoV-2 is now established as the cause of coronavirus disease 2019 (now named COVID-19), a respiratory illness, it has also become clear that some people with SARS-CoV-2 infection may exhibit no symptoms at all. We report the clinical characteristics and course of three asymptomatic patients who contracted SARS-CoV-2 infection on the cruise ship, Diamond Princess. The three patients did not have any symptoms at admission, however, all showed bilateral groundglass opacities, predominantly distributed in the lung periphery, with occasional consolidation, on the plain chest radiograph. All three showed a smooth clinical course, and remained asymptomatic throughout the course of the infection. These cases serve to emphasize that patients without any symptoms could have COVID-19 pneumonia, and should be noted the possibility that mild cases and early onset of severe cases are included even in asymptomatic patients. According to one published paper, chest CT may be useful for early detection of COVID-19 pneumonia. In addition, other reports have documented the changes on chest CT associated with COVID-19 pneumonia from onset until recovery. From our experience of these cases and the published reports mentioned above, we consider that CT may be useful for the diagnosis of COVID-19 and determining the timing of onset of the disease.

The patient, an 83-year-old woman, lived with her daughter, at whose workplace, a person had been diagnosed as having COVID-19. The daughter was admitted to the hospital for pneumonia, however, the results of the PCR test for SARS-CoV-2 performed twice were negative. The patient developed fever a few days later, and visited an outpatient clinic for patients with fever and a history of travel abroad. The result of a nasal swab PCR test was negative, and antibiotics were prescribed. While the fever gradually subsided,the patient began to experience dyspnea. Therefore, she visited the outpatient clinic again for a repeat nasal swab test. Meanwhile, the dyspnea became severe and she was transported to our hospital. Immediately after admission, she was intubated and initiated on mechanical ventilation. A nasal swab and a specimen of lower respiratory tract secretions were submitted for COVID-19 testing by PCR, and while the nasal swab test result was negative again, the lower respiratory tract specimen yielded a positive result.
The possibility of false-negative results of PCR testing for SARS-CoV-2 should be borne in mind in close contacts or strongly suspected cases of COVID-19. PCR testing of specimens of lower respiratory tract secretions might be necessary for suspected cases of COVID-19 pneumonia.

The patient was a 56-year-old man who presented with a 14-day history of fever, and had been diagnosed by a physician as having pneumonia on the basis of the findings of chest CT. He had not travelled abroad and gave no history of close contact with any patients with suspected or confirmed COVID-19. His chest CT showed bilateral multiple ground-glass opacities, distributed predominantly in the peripheral lung regions. We suspected COVID-19 pneumonia based on the chest CT findings. A nasopharyngeal swab PCR test (PCR) for SARS-CoV-2 on day 1 returned a negative result. The following day, a nasopharyngeal swab and a sputum specimen were submitted for repeat PCR testing, and both yielded positive results, confirming the diagnosis of COVID-19 pneumonia in the patient.

This is a case report of a male patient in his 50s who developed pneumonia while he was admitted at another hospital. The patient received antibacterial drugs, but showed no improvement. He was referred to our hospital for further investigation and treatment of pneumonia. We made the diagnosis of COVID-19 promptly, based on the clinical history, laboratory results, and chest CT findings.
This case highlights the importance of carefully observing the patientʼs clinical course and performing appropriate examinations to make a prompt diagnosis of COVID-19.

Our hospital was introduced in the media as the hospital at which the first patient who died of COVID-19 infection in Japan was hospitalized. Patients with pneumonia associated with COVID-19 sometimes show rapid deterioration of the respiratory status, with a poor prognosis. The cases encountered by us that we report here also needed intensive long-term respiratory management. ARDS is an important pathological condition complicating COVID-19 pneumonia. From the perspective of the continuing pathology of ARDS, we treated the patients with a steroid and sivelestat. However, it became clear that the respiratory pathology in the patients could not be adequately addressed by the uniform treatment protocol for ARDS. In conclusion, inpatient treatment in a local community-based small hospital without an ICU can be extremely difficult.

We report the case of an 85-year-old woman who was transported to our hospital by ambulance with progressively worsening dyspnea and hypoxia. She had no history of contact with any patient with coronavirus disease 2019 (COVID-19). The peripheral arterial oxygen saturation level on a 10L/min nonrebreather-type mask was as low as 80%. Chest auscultation revealed coarse crackles. After emergency intubation, it was surmised that the probability of heart failure was low because of the lack of pink, frothy sputum. Bacterial pneumonia was also considered to be unlikely, as the sputum was not purulent. Moreover,laboratory data revealed a normal white blood cell count (6,100/μL) and no elevation of the serum procalcitonin level (0.63ng/mL), which were also consistent with the condition not likely to be a bacterial infection. Pulmonary thromboembolism was ruled out by the presence of coarse crackles on chest auscultation and normal blood pressure. Thereafter, the possibility of COVID-19 was considered and the patient was immediately isolated. Two days later, the polymerase chain reaction test for COVID-19 returned positive. There was no evidence of transmission of the virus to the healthcare personnel who had treated this patient, including the 6 with medium-risk exposure, during the 3-week period after the exposure. In the COVID-19 pandemic era, rapid differential diagnosis of hypoxia is essential to prevent further transmission of SARS-CoV-2 infection. Our case highlights the importance of the sputum appearance/characteristics and laboratory data for rapidly ruling out diseases other than COVID-19.

As no specific therapeutic agents have been established yet for coronavirus disease 2019 (COVID-19),the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic therapy is the mainstay of treatment. Although the “Concept of antiviral treatment for COVID-19, First edition” published by the Japanese Association for Infectious Diseases recommends the use of antiviral medication for infected individuals over the age of 50 years, we have documented the case of a 73-year-old woman with COVID-19 pneumonia who improved without antiviral medication. The patient became infected with SARS-CoV-2 on the cruise ship, Diamond Princess, and first tested positive for SARS-CoV-2, by the RT-PCR test, on February 15, 2020. She was admitted to another hospital with fever and pneumonia on February 16, and on February, the pneumonia worsened in severity, she was transferred to our hospital. However, her condition improved spontaneously within a few days, without any antiviral medication. This report is very valuable for documenting the natural history of COVID-19 pneumonia and can be considered as a reference case for formulating strategies for antiviral drug administration for COVID-19 patients in the future.

We describe three patients with coronavirus disease 2019 (COVID-19) pneumonia, including an elderly woman and two of her family members, who contracted the infection from a healthcare worker. Case 1, an 89-year old woman；this patient contracted the infection from a healthcare worker. Case 2, a 67-year old man, and Case 3, a 67-year old woman, were family members who contracted the infection from Case 1. The serial interval of the disease between Case 1 and Case 2/Case 3 was 4 days. All three patients had high fever, lymphocytopenia, and multiple bilateral pulmonary ground-glass opacities. Health care facilities are thought to be at a high risk of becoming clusters of infection. Family members of elderly are thought to be at a high risk of contracting infection from the elderly while serving as their caregivers in the house.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel virus, SARS-CoV-2. The clinical spectrum of COVID-19 varies from asymptomatic infection to severe pneumonia. The COVID-19 epidemic started at the end of 2019 in Wuhan, China, and the disease has now spread to the entire world. The rapid spread of the infection worldwide led the WHO to declare the outbreak a pandemic on March 11,2020. Herein, we report three patients with COVID-19 admitted to Atsugi City Hospital, who contracted the infection on the cruise ship, Diamond Princess, which was one of the early sites of outbreak of COVID-19. The three patients had different backgrounds, including age, sex and underlying disease profile, and each had a different clinical course. However, all three tested persistently positive by the PCR test for more than 4 weeks, which is longer than the average reported period of positivity. In this report, we discuss the interpretation of persistently positive results of PCR for SARS-CoV-19, the appropriate instructions for these patients, and the optimal timing of discharge home of these patients, considering the available medical resources.

We report the case of a patient with pneumonia caused by the new coronavirus (COVID-19 pneumonia),who contracted the novel coronavirus (SARS-CoV-2) infection on a large cruise ship, and was hospitalized due to fever and cough. The fever resolved immediately after admission, however, a mild cough persisted. Chest CT showed multiple ground-glass opacities in the upper and lower lobes of both lungs. However, we judged that the patient was at a low risk of exacerbation of the disease as he was young, and did not administer any antiviral drugs. Since the subjective symptoms improved, we repeated the SARS-CoV-2 PCR test on day 9 after the onset of the illness, but the result was still positive. As the patient was observed to have sinus stenosis in the left nasal cavity at the time of collection of the nasopharyngeal swab for testing, sinus CT was performed. The findings were suggestive of inflammation of the left nasal mucosa, ethmoid sinusitis,and maxillary sinusitis. It took a long 41 days before we could finally confirm two consecutive negative results of the nasopharyngeal swab PCR test for the novel virus. It has not yet been clarified whether the SARS-CoV2-19 virus can cause rhinitis and/or sinusitis, but from our experience of this case, we believe that SARS-CoV2-19 can colonize already infected nasal mucosa and sinuses for a prolonged period of time. It is necessary to pay attention to this aspect, as it may prolong the disease duration and/or increase the risk of relapse.

Coronavirus infection 2019 (COVID-19) is a respiratory infection caused by a novel coronavirus (SARS-CoV-2) that was first reported in Wuhan, China, in December 2019. In Japan, since mid-February 2020, there have been a series of reports of COVID-19 outbreaks among people without apparent contact with COVID-19 patients or visitors to Japan from endemic areas, or a recent history of visiting an endemic area. We encountered a patient with COVID-19 arising from local community transmission of infection, who presented with the chief complaints of fatigue and anorexia. In this patient, a quantitative polymerase chain reaction (PCR) assay showed a higher viral load and a more extended period of viral excretion in nasopharyngeal swab specimens than in pharyngeal swab specimens. When using a PCR assay as a diagnostic test or as an indicator of improvement, we should be aware of the characteristics and limitations of the test.

Real-time polymerase chain reaction (RT-PCR) assay is used for the diagnosis of novel coronavirus disease 2019 (COVID-19), and for identifying those patients with COVID-19 who have recovered but may require ongoing isolation. We report two cases of COVID-19 in whom the RT-PCR test remained persistently positive until 16 and 19 days after resolution of the symptoms (33 and 28 days after the onset of symptoms), respectively. While the viral load in the respiratory specimens had decreased after resolution of the symptoms, the RT-PCR test result continued to be positive. Mucoid sputum samples obtained by handing containers to the patient returned positive results for even longer periods than nasal swab samples. Our findings have led us to question the usefulness of the RT-PCR assay for determining the appropriate time to release patients from isolation after they show symptomatic recovery. RT-PCR performed using mucoid sputum samples was also sensitive and safe, because of the low exposure of the healthcare workers to the virus while collecting the test samples.
Both authors contributed equally to this study.

We report the case of a hemodialysis patient diagnosed as having COVID-19. He was emergently transferred to our hospital, which is a designated infectious diseases hospital with facilities for hemodialysis. The pneumonia had progressed steadily until he was transferred to our hospital. However, with the start of hydroxychloroquine sulfate (trade name：Plakenil) administration at our hospital, his condition began to show significant improvement. He was discharged from our hospital on day 19 of admission. Chloroquine has been used for many years as a drug for the treatment and prevention for malaria. In recent years, hydroxychloroquine has been used for the treatment of collagen vascular diseases, such as cutaneous and systemic lupus erythematosus. Chloroquine phosphate was used to treat severe acute respiratory syndrome (SARS) during the 2002-2003 epidemic of the disease. China reported clinical efficacy of chloroquine phosphate for the treatment of COVID-19. Chloroquine has been demonstrated to exert antiviral activity against SARS-CoV-2 in vitro, and is considered to control excessive inflammation in vivo due to its immunomodulatory activity. In our patient reported here, we used the drug at the same dosage as that used for the treatment of cutaneous and systemic lupus erythematosus. Although there remains the possibility that the patientʼs condition improved spontaneously in the natural course of the disease, we consider that hydroxychloroquine may have been effective. There is no established treatment for COVID-19, and numerous empiric treatments have been attempted. There have been few reports from Japan of the use of hydroxychloroquine for the treatment of COVID-19, and further accumulation of cases is necessary.

A 38-year-old man diagnosed as having COVID-19 pneumonia was transferred to our hospital from another hospital. The patient had received favipiravir at the previous hospital, and as he still had severe respiratory dysfunction, we added hydroxychloroquine and azithromycin to the treatment regimen for COVID-19 pneumonia at our hospital. The respiratory status improved gradually with the treatment and the patient began to be weaned from mechanical ventilation. However, on the 5^th hospital day, the patient developed ventricular fibrillation (Vf) and cardiac arrest, with return of spontaneous circulation (ROSC) 2 minutes after the start of cardiopulmonary resuscitation. An electrocardiogram recorded after the ROSC showed not QT interval prolongation, but first-degree atrioventricular block. Nevertheless, because both hydroxychloroquine and azithromycin could cause QT interval prolongation, both were discontinued and the Vf did not recur. The patient was transferred to another hospital after extubation and had no neurological deficit. Herein, we report a patient with COVID-19 pneumonia who developed Vf while being treated with hydroxychloroquine,azithromycin and favipiravir.

A man in his fifties visited another hospital with fever and cough. The patient was diagnosed as having coronavirus disease 2019 (COVID-19) on the basis of the results of a reverse transcription polymerase chain reaction (RT-PCR) test. Chest CT revealed multiple ground-glass opacities in both the lower lobes. Subsequently, the patient developed dyspnea and was initiated on oxygen supplementation via a nasal cannula. Chest CT showed rapid progression of the ground-glass opacities and consolidation in both lower lung lobes,and the patient was started on treatment with favipiravir. At this stage, he was transferred to our hospital for intensive care. Two days after he was transferred, the condition progressed to acute respiratory failure,necessitating mechanical ventilation. The serum D-dimer levels were significantly increased (115μg/mL). In addition to exacerbation of the primary lung disease, we diagnosed the patient as also having acute pulmonary embolism and mediastinal emphysema on the basis of the findings on a CT obtained after intravenous administration of contrast material, and he was started on therapy with an anticoagulant. He became hypotensive and required norepinephrine and vasopressin, and also developed severe acute kidney injury. His lung condition gradually improved, and on day 12 after he was intubated, he was successfully weaned from mechanical ventilation. We have presented a report of this case owing to the extremely rapid progression of the disease in this patient.

The current criteria for COVID-19 diagnosis include a history of close contact with a known patient and clinical manifestations such as fever and respiratory symptoms. However, we do not believe that all patients with COVID-19 would meet the abovementioned criteria. Herein, we describe a case of COVID-19 in which the patient did not meet the above diagnostic criteria. The patient was a man in his thirties, who presented with a history of persistent back pain and fever (38̊C). He was referred to us for suspected pyogenic spondylitis. Chest X-ray and computed tomography revealed multifocal reticular shadows in both lungs, compatible with COVID-19 pneumonia. He had no history of close contact with a COVID-19 patient or any respiratory symptoms, but a polymerase chain reaction (PCR) test yielded positive results for SARS-CoV-2. We suggest that all patients should be medically evaluated on admission to exclude COVID-19 pneumonia, to avoid the risk of misdiagnosis that could result in further transmission of infection, even in the absence of a history of close contact with COVID-19 patients or respiratory symptoms.