現在新型コロナウイルス感染症（COVID-19）では50 歳以上で低酸素血症を認めた段階で他疾患に適応のある抗ウイルス薬の投与が推奨されている．しかし治療が必要となる重症化因子についての検討は少ない．今回COVID-19 により入院した患者で抗ウイルス薬による治療を必要とした群と経過観察のみで改善した群を後方視的に検討し，抗ウイルス薬が必要となる臨床所見について検討した．まず当院に入院した49 例のCOVID-19 感染患者について，A 群：無症候性病原体保有者，B 群：症状あり，ウイルス肺炎像なし，C 群：ウイルス肺炎像あり，呼吸不全なし，D 群：ウイルス肺炎像あり，呼吸不全あり，に分類した．C 群は無治療で軽快し，D 群では抗ウイルス薬治療が行われた．重症度と相関した背景因子と症状は年齢，合併症の有無，喫煙歴，発熱，下痢であったが，治療を必要としたD 群に特徴的な所見は喫煙歴のみであった．次に重症度と相関した臨床検査値はPaO₂，リンパ球数，D-dimer，AST，CK，LDH，CRP，PCT，ferritin であったが，多変量解析で治療必要群と有意に相関した検査値はリンパ球数，CRP，ferritin となった．両群を区別するカットオフ値をROC 曲線より求めると，リンパ球数1,200/μL 以下，CRP 2.38mg/dL 以上，ferritin 394ng/mL 以上となった．画像所見では，抗ウイルス薬治療を要しなかったC 群と要したD 群とを最もよく区別する所見は浸潤影の有無だった．以上よりこれらの重症化因子は呼吸不全への進展を考慮すべき臨床指標になると思われた．また喫煙歴，リンパ球数1,200/μL 以下，CRP 2.5mg/dL 以上，ferritin 400ng/mL 以上，CT 上の浸潤影の5 つをリスク因子として選ぶと発症からPCR 陰性化までの日数と強い相関を示した（p＜0.0001）．

2019 年12 月に中国湖北省武漢市で発生した新型コロナウイルス感染症は，急激な勢いで世界中へ拡大し，本邦でも明らかな感染経路の特定できない症例が増加している．当院は第二種感染症指定医療機関であり，45 症例のCOVID-19 感染症を経験した．平均年齢は50.6 歳で，男性33 名，女性12 名であった．発熱は39 名86.7％），咳嗽は33 名（73.3％），倦怠感は24 名（53.3％），下痢は5 名（11.1％）で認めた．また，患者増加に伴う医療崩壊を回避するために神奈川県が構築した神奈川モデルにおける重症度分類に当てはめると，軽症30 名，中等症14 名，重症1 名であった．経過中に軽症から中等症へ悪化した症例は1/30 名（3.3％）であり，中等症から重症に悪化した症例は6/14 名（42.9％）であった．軽症は自宅または宿泊施設等での療養，中等症以上は医療機関での入院となるため，患者搬送先を決める上で神奈川モデルにおける重症度分類は，その後の臨床経過を踏まえると妥当な分類であることが示唆された．

新型コロナウイルス感染症（COVID-19）の診断に，血液由来検体を用いた抗体検査法（イムノクロマト法）の実用化が期待されている．今回我々は，PCR 検査でCOVID-19 と確定診断された52 症例を対象に，新型コロナウイルス（SARS-CoV-2）抗体検査試薬キット（IgM 抗体検出キット，IgG 抗体検出キット）の陽性となる時期・割合を検討した． 最終的には，COVID-19 と確定診断された患者全例で抗体陽性が確認された．IgM 抗体が陽性化したのは，症状発現から平均11.9 日（最短5 日，中央値11 日）であった．IgG 抗体が陽性化したのは，症状発現から平均11.2 日（最短5 日，中央値11 日）であった．IgM キットとIgG キットを比較し，陽性化率・陽性化までの期間に有意差はなかったが，IgM がIgG に先行して陽性化する例はなく，IgM とIgG が同時陽性45 例（87%），IgG がIgM に先行して陽性7 例（13%）であった．SARS-CoV-2PCR 検査陰性で，その後の経過よりCOVID-19 ではないと診断した急性期発熱・肺炎患者35 例を対象とした検証では，6 例（17.1%）で抗IgG 抗体が陽性，1 例（2.8%）で抗IgM 抗体が陽性であった． 我々の検討結果は極めて限定的なものであり，この試薬の性能評価に帰結するものではない．イムノクロマト法による抗体検査試薬検査の今後が期待されるが，現時点ではあくまでPCR 検査に補完的な検査手法として慎重な対応が求められると考えられた．

新型コロナウイルス感染症（COVID-19）の拡大によって，入院病床の確保が逼迫する問題となっている. 指定感染症であるCOVID-19 は，一定の基準に則って入退院の決定がなされており，入院期間は長期にわたる．大型クルーズ船によるCOVID-19 集団感染事例において，当院では軽症者を含む11 例のCOVID-19 感染症症例を経験したため，臨床経過から重症化因子と入院期間の延長に関わる因子を考察した.重症度は中国CDC の分類を用いて決定した．11 例の年齢中央値は62 歳，男性4 例・女性7 例で，軽症（mild）が 7 例，中等症（severe）が4 例，重症（critical）が0 例であった.発症から軽快の基準を満たすまでの日数の中央値は，中等症例13 日・軽症例7 日であった.発症からPCR の陰性化が確認できるまでの日数の中央値は，中等症例16 日・軽症例14 日であった.発症から退院までの日数は，中等症例22.5 日・軽症例16 日であった．COVID-19 症例は軽快した後も一部の症例でPCR 検査の陽性が継続し，入院期間の長期化の一因と考えられた.また，中等症例と軽症例を比較すると，中等症例は軽症例に比して入院時の血清フェリチンや血清アミロイドA 蛋白が高い傾向があった．COVID-19 症例の増加による病床数の確保が必要な状況においては，軽症例や入院後に軽快した症例の自宅・宿泊療養が検討される.また経過中に重症化する症例を適切に判別する方法を確立し，治療や二次感染防止のための入院・退院基準に反映することが必要であると考える.

感染経路が不明なcoronavirus disease 2019（COVID-19：SARS-CoV-2 感染症）の症例が日本の各地で報告されつつある．市中で，咽頭痛や咳などの上気道症状，発熱などを呈する症例に遭遇した場合に，COVID-19 の可能性をどの程度考慮するかは難しい．市中で発症しSARS-CoV-2 のPCR 検査を施行し陽性が確認されたCOVID-19 肺炎10 症例について，経過，症状，検査所見，画像所見を検討した．38℃以上の発熱90%，鼻汁10%，咽頭痛40%，咳80%，痰50%，息切れ60%，倦怠感70%，消化器症状を30% に認めた．家族に体調不良，発熱を認めたのは50% であった．症状出現から診断まで5～12 日，受診回数1～3 回であった．聴診所見は1 症例のみcoarse crackles を認め，SpO₂ は8 割で95% 以上，2 割で80% であった．いずれの症例も白血球数増多はなく，リンパ球数減少（1,000/μL 未満）を60% に認めた．CRP は70% で5mg/dL 以下の軽度上昇にとどまり，50% でD-dimer の軽微な上昇を認めた．CT では全ての症例で，両側，多発性のスリガラス様陰影を認めた．末梢の胸膜直下に優位な分布，右下葉にも病変が存在する割合は90% であった．①同居者に体調不良者がいる，②38℃以上の発熱，③リンパ球数の減少，④特徴的なCT 所見，⑤CT で肺炎を認めるが白血球数や好中球数の増多を認めない，の数項目があてはまる場合，市中で遭遇する感染症においてCOVID-19 肺炎の可能性が高いと考えられた．

新型コロナウイルス陽性患者は，2020 年4 月5 日現在，無症状や軽症者では自宅待機も可能な指針が出されているものの，多くの患者が入院管理対象となっている．我々は，ダイヤモンド・プリンセス号からの新型コロナウイルス陽性患者を受け入れた．軽症の6 例に注目し，入院時のCT 結果，臨床経過，血液検査，rRT-PCR 検査の陰性化までの期間，入院期間について評価を行ったため報告する．

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.