今日の臨床サポート

COVID-19(新型コロナウイルス感染症)

著者: 石川和宏 聖路加国際病院 感染症科

著者: 松尾貴公 聖路加国際病院 感染症科

著者: 森信好 聖路加国際病院 感染症科

監修: 上原由紀 聖路加国際病院 臨床検査科/感染症科

著者校正/監修レビュー済:2020/11/16
参考ガイドライン:
  1. 国立感染症研究所:新型コロナウイルス感染症に対する感染管理新型コロナウイルス感染症に対する感染管理(2020年6月2日改訂版)
  1. 国立感染症研究所:新型コロナウイルス感染症、自宅療養時の健康・感染管理(2020年4月2日)
  1. 厚生労働省:新型コロナウイルス感染症について
  1. WHO:Coronavirus
  1. CDC:Coronavirus (COVID-19)
  1. IDSA:Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19

概要・推奨   

  1. COVID-19はコロナウイルスの一種であるSARS-CoV-2による感染症で、2019年12月頃に中国湖北省武漢市で発生したが、現在は世界中に広がっている。
  1. 診断は主に鼻咽頭ぬぐい液のPCRで行われる。COVID-19患者との濃厚接触、長期間続く上気道症状、嗅覚障害などがある場合は検査を考慮する。また、胸部CT検査では特徴的なパターンをとることも多く診断の手助けとなる。
  1. 確立された治療はなく、支持療法が中心だが、現在、さまざまな臨床研究が行われており効果が期待される。2020年5月7日にベクルリー点滴静注液/点滴静注用(レムデシビル)が薬剤承認された。また薬剤承認はされていないが、「厚生労働省の新型コロナウイルス 感染症(COVID-19)診療の手引き」にデキサメタゾンも掲載された。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
石川和宏 : 特に申告事項無し[2021年]
松尾貴公 : 特に申告事項無し[2021年]
森信好 : 特に申告事項無し[2021年]
監修:上原由紀 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 新型コロナウイルス感染症に対して様々な臨床試験の結果が公表され治療選択肢が増え、レムデシビルやデキサメタゾンが厚生労働省からも推奨されるようになった。

病態・疫学・診察

イントロダクション  
  1. 新型コロナウイルス(以下、SARS-CoV-2)は、2019年12月以降中華人民共和国湖北省武漢市で発生した原因不明の肺炎患者から検出された新種のコロナウイルスである。
  1. 世界保健機関(WHO)は新型コロナウイルス感染症の正式名称を「COVID-19(coronavirus disease 2019)」と定めた(以下、COVID-19)。
疫学  
  1. コロナウイルスはプラス鎖一本鎖のRNAをウイルスゲノムとして有するエンベロープウイルスである。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

著者: Stephen A Lauer, Kyra H Grantz, Qifang Bi, Forrest K Jones, Qulu Zheng, Hannah R Meredith, Andrew S Azman, Nicholas G Reich, Justin Lessler
雑誌名: Ann Intern Med. 2020 Mar 10;. doi: 10.7326/M20-0504. Epub 2020 Mar 10.
Abstract/Text Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities.
Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications.
Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020.
Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China.
Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China.
Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization.
Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine.
Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases.
Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases.
Primary Funding Source: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

PMID 32150748  Ann Intern Med. 2020 Mar 10;. doi: 10.7326/M20-0504. Ep・・・
著者: Xi He, Eric H Y Lau, Peng Wu, Xilong Deng, Jian Wang, Xinxin Hao, Yiu Chung Lau, Jessica Y Wong, Yujuan Guan, Xinghua Tan, Xiaoneng Mo, Yanqing Chen, Baolin Liao, Weilie Chen, Fengyu Hu, Qing Zhang, Mingqiu Zhong, Yanrong Wu, Lingzhai Zhao, Fuchun Zhang, Benjamin J Cowling, Fang Li, Gabriel M Leung
雑誌名: Nat Med. 2020 Apr 15;. doi: 10.1038/s41591-020-0869-5. Epub 2020 Apr 15.
Abstract/Text We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

PMID 32296168  Nat Med. 2020 Apr 15;. doi: 10.1038/s41591-020-0869-5. ・・・
著者: Roman Wölfel, Victor M Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange, Marcel A Müller, Daniela Niemeyer, Terry C Jones, Patrick Vollmar, Camilla Rothe, Michael Hoelscher, Tobias Bleicker, Sebastian Brünink, Julia Schneider, Rosina Ehmann, Katrin Zwirglmaier, Christian Drosten, Clemens Wendtner
雑誌名: Nature. 2020 May;581(7809):465-469. doi: 10.1038/s41586-020-2196-x. Epub 2020 Apr 1.
Abstract/Text Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

PMID 32235945  Nature. 2020 May;581(7809):465-469. doi: 10.1038/s41586・・・
著者: Neeltje van Doremalen, Trenton Bushmaker, Dylan H Morris, Myndi G Holbrook, Amandine Gamble, Brandi N Williamson, Azaibi Tamin, Jennifer L Harcourt, Natalie J Thornburg, Susan I Gerber, James O Lloyd-Smith, Emmie de Wit, Vincent J Munster
雑誌名: N Engl J Med. 2020 Apr 16;382(16):1564-1567. doi: 10.1056/NEJMc2004973. Epub 2020 Mar 17.
Abstract/Text
PMID 32182409  N Engl J Med. 2020 Apr 16;382(16):1564-1567. doi: 10.10・・・
著者: Jane Y Tong, Amanda Wong, Daniel Zhu, Judd H Fastenberg, Tristan Tham
雑誌名: Otolaryngol Head Neck Surg. 2020 Jul;163(1):3-11. doi: 10.1177/0194599820926473. Epub 2020 May 5.
Abstract/Text OBJECTIVE: To determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID-19).
DATA SOURCES: Literature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID-19 patients.
REVIEW METHODS: Search strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID-19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta-analysis using pooled prevalence estimates in a random-effects model were calculated.
RESULTS: Ten studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%-75.23%) prevalence among patients with COVID-19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%-68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%-57.24%) and 86.60% (95% CI, 72.95%-95.95%) prevalence, respectively.
CONCLUSIONS: Olfactory and gustatory dysfunction are common symptoms in patients with COVID-19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta-analysis to report on the prevalence of these symptoms in COVID-19 patients.

PMID 32369429  Otolaryngol Head Neck Surg. 2020 Jul;163(1):3-11. doi: ・・・
著者: Christopher S von Bartheld, Molly M Hagen, Rafal Butowt
雑誌名: ACS Chem Neurosci. 2020 Oct 7;11(19):2944-2961. doi: 10.1021/acschemneuro.0c00460. Epub 2020 Sep 17.
Abstract/Text A significant proportion of people who test positive for COVID-19 have chemosensory deficits. However, the reported prevalence of these deficits in smell and taste varies widely, and the reason for the differences between studies is unclear. We determined the pooled prevalence of such chemosensory deficits in a systematic review and meta-analysis. We searched the COVID-19 portfolio of the National Institutes of Health for studies that reported the prevalence of smell or taste deficits or both in patients diagnosed with COVID-19. One-hundred-four studies reporting on 38 198 patients qualified and were subjected to a systematic review and meta-analysis. Estimated random prevalence of olfactory dysfunction was 43.0%, that of taste dysfunction was 44.6%, and that of overall chemosensory dysfunction was 47.4%. We examined the effects of age, gender, disease severity, and ethnicity on chemosensory dysfunction. Prevalence of smell or taste dysfunction or both decreased with older age, male gender, and disease severity. Ethnicity was highly significant: Caucasians had a three times higher prevalence of chemosensory dysfunctions (54.8%) than Asians (17.7%). The finding of geographic differences points to two causes that are not mutually exclusive. A virus mutation (D614G) may cause differing infectivity, while at the host level genetic, ethnicity-specific variants of the virus-binding entry proteins may facilitate virus entry in the olfactory epithelium and taste buds. Both explanations have major implications for infectivity, diagnosis, and management of the COVID-19 pandemic.

PMID 32870641  ACS Chem Neurosci. 2020 Oct 7;11(19):2944-2961. doi: 10・・・
著者: Joshua M Levy
雑誌名: JAMA Otolaryngol Head Neck Surg. 2020 Jul 2;. doi: 10.1001/jamaoto.2020.1378. Epub 2020 Jul 2.
Abstract/Text
PMID 32614399  JAMA Otolaryngol Head Neck Surg. 2020 Jul 2;. doi: 10.1・・・
著者: Zunyou Wu, Jennifer M McGoogan
雑誌名: JAMA. 2020 Feb 24;. doi: 10.1001/jama.2020.2648. Epub 2020 Feb 24.
Abstract/Text
PMID 32091533  JAMA. 2020 Feb 24;. doi: 10.1001/jama.2020.2648. Epub 2・・・
著者: CDC COVID-19 Response Team
雑誌名: MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346. doi: 10.15585/mmwr.mm6912e2. Epub 2020 Mar 27.
Abstract/Text Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.

PMID 32214079  MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346. ・・・
著者: Dawei Wang, Bo Hu, Chang Hu, Fangfang Zhu, Xing Liu, Jing Zhang, Binbin Wang, Hui Xiang, Zhenshun Cheng, Yong Xiong, Yan Zhao, Yirong Li, Xinghuan Wang, Zhiyong Peng
雑誌名: JAMA. 2020 Feb 7;. doi: 10.1001/jama.2020.1585. Epub 2020 Feb 7.
Abstract/Text Importance: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
Objective: To describe the epidemiological and clinical characteristics of NCIP.
Design, Setting, and Participants: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.
Exposures: Documented NCIP.
Main Outcomes and Measures: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.
Results: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
Conclusions and Relevance: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

PMID 32031570  JAMA. 2020 Feb 7;. doi: 10.1001/jama.2020.1585. Epub 20・・・
著者: Qun Li, Xuhua Guan, Peng Wu, Xiaoye Wang, Lei Zhou, Yeqing Tong, Ruiqi Ren, Kathy S M Leung, Eric H Y Lau, Jessica Y Wong, Xuesen Xing, Nijuan Xiang, Yang Wu, Chao Li, Qi Chen, Dan Li, Tian Liu, Jing Zhao, Man Liu, Wenxiao Tu, Chuding Chen, Lianmei Jin, Rui Yang, Qi Wang, Suhua Zhou, Rui Wang, Hui Liu, Yinbo Luo, Yuan Liu, Ge Shao, Huan Li, Zhongfa Tao, Yang Yang, Zhiqiang Deng, Boxi Liu, Zhitao Ma, Yanping Zhang, Guoqing Shi, Tommy T Y Lam, Joseph T Wu, George F Gao, Benjamin J Cowling, Bo Yang, Gabriel M Leung, Zijian Feng
雑誌名: N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.
Abstract/Text BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.
METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.
RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).

Copyright © 2020 Massachusetts Medical Society.
PMID 31995857  N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.10・・・
著者: Chaolin Huang, Yeming Wang, Xingwang Li, Lili Ren, Jianping Zhao, Yi Hu, Li Zhang, Guohui Fan, Jiuyang Xu, Xiaoying Gu, Zhenshun Cheng, Ting Yu, Jiaan Xia, Yuan Wei, Wenjuan Wu, Xuelei Xie, Wen Yin, Hui Li, Min Liu, Yan Xiao, Hong Gao, Li Guo, Jungang Xie, Guangfa Wang, Rongmeng Jiang, Zhancheng Gao, Qi Jin, Jianwei Wang, Bin Cao
雑誌名: Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
Abstract/Text BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.
METHODS: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.
FINDINGS: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.
INTERPRETATION: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.
FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 31986264  Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0・・・
著者: Xiaobo Yang, Yuan Yu, Jiqian Xu, Huaqing Shu, Jia'an Xia, Hong Liu, Yongran Wu, Lu Zhang, Zhui Yu, Minghao Fang, Ting Yu, Yaxin Wang, Shangwen Pan, Xiaojing Zou, Shiying Yuan, You Shang
雑誌名: Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
Abstract/Text BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia.
METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation.
FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients.
INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced.
FUNDING: None.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32105632  Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/・・・
著者: Chaomin Wu, Xiaoyan Chen, Yanping Cai, Jia'an Xia, Xing Zhou, Sha Xu, Hanping Huang, Li Zhang, Xia Zhou, Chunling Du, Yuye Zhang, Juan Song, Sijiao Wang, Yencheng Chao, Zeyong Yang, Jie Xu, Xin Zhou, Dechang Chen, Weining Xiong, Lei Xu, Feng Zhou, Jinjun Jiang, Chunxue Bai, Junhua Zheng, Yuanlin Song
雑誌名: JAMA Intern Med. 2020 Mar 13;. doi: 10.1001/jamainternmed.2020.0994. Epub 2020 Mar 13.
Abstract/Text Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died.
Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020.
Exposures: Confirmed COVID-19 pneumonia.
Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed.
Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).
Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

PMID 32167524  JAMA Intern Med. 2020 Mar 13;. doi: 10.1001/jamainternm・・・
著者: Saskia Middeldorp, Michiel Coppens, Thijs F van Haaps, Merijn Foppen, Alexander P Vlaar, Marcella C A Müller, Catherine C S Bouman, Ludo F M Beenen, Ruud S Kootte, Jarom Heijmans, Loek P Smits, Peter I Bonta, Nick van Es
雑誌名: J Thromb Haemost. 2020 Aug;18(8):1995-2002. doi: 10.1111/jth.14888. Epub 2020 Jul 27.
Abstract/Text BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications.
OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19.
METHODS: Single-center cohort study of 198 hospitalized patients with COVID-19.
RESULTS: Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days).
CONCLUSIONS: The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
PMID 32369666  J Thromb Haemost. 2020 Aug;18(8):1995-2002. doi: 10.111・・・
著者: F A Klok, M J H A Kruip, N J M van der Meer, M S Arbous, D Gommers, K M Kant, F H J Kaptein, J van Paassen, M A M Stals, M V Huisman, H Endeman
雑誌名: Thromb Res. 2020 Jul;191:148-150. doi: 10.1016/j.thromres.2020.04.041. Epub 2020 Apr 30.
Abstract/Text INTRODUCTION: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses.
METHODS: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.
RESULTS: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).
CONCLUSION: In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Copyright © 2020. Published by Elsevier Ltd.
PMID 32381264  Thromb Res. 2020 Jul;191:148-150. doi: 10.1016/j.thromr・・・
著者: David Kim, James Quinn, Benjamin Pinsky, Nigam H Shah, Ian Brown
雑誌名: JAMA. 2020 Apr 15;. doi: 10.1001/jama.2020.6266. Epub 2020 Apr 15.
Abstract/Text
PMID 32293646  JAMA. 2020 Apr 15;. doi: 10.1001/jama.2020.6266. Epub 2・・・
著者: Daniel A Solomon, Amy C Sherman, Sanjat Kanjilal
雑誌名: JAMA. 2020 Oct 6;324(13):1342-1343. doi: 10.1001/jama.2020.14661.
Abstract/Text
PMID 32797145  JAMA. 2020 Oct 6;324(13):1342-1343. doi: 10.1001/jama.2・・・
著者: Lirong Zou, Feng Ruan, Mingxing Huang, Lijun Liang, Huitao Huang, Zhongsi Hong, Jianxiang Yu, Min Kang, Yingchao Song, Jinyu Xia, Qianfang Guo, Tie Song, Jianfeng He, Hui-Ling Yen, Malik Peiris, Jie Wu
雑誌名: N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19.
Abstract/Text
PMID 32074444  N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.10・・・
著者: Wenling Wang, Yanli Xu, Ruqin Gao, Roujian Lu, Kai Han, Guizhen Wu, Wenjie Tan
雑誌名: JAMA. 2020 Mar 11;. doi: 10.1001/jama.2020.3786. Epub 2020 Mar 11.
Abstract/Text
PMID 32159775  JAMA. 2020 Mar 11;. doi: 10.1001/jama.2020.3786. Epub 2・・・
著者: Yang Pan, Daitao Zhang, Peng Yang, Leo L M Poon, Quanyi Wang
雑誌名: Lancet Infect Dis. 2020 Apr;20(4):411-412. doi: 10.1016/S1473-3099(20)30113-4. Epub 2020 Feb 24.
Abstract/Text
PMID 32105638  Lancet Infect Dis. 2020 Apr;20(4):411-412. doi: 10.1016・・・
著者: E Pasomsub, S P Watcharananan, K Boonyawat, P Janchompoo, G Wongtabtim, W Suksuwan, S Sungkanuparph, A Phuphuakrat
雑誌名: Clin Microbiol Infect. 2020 May 15;. doi: 10.1016/j.cmi.2020.05.001. Epub 2020 May 15.
Abstract/Text OBJECTIVES: Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19.
METHODS: From 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared.
RESULTS: Two-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%-96.6%), and 98.9% (95% CI 96.1%-99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (κ coefficient 0.851, 95% CI 0.723-0.979; p < 0.001).
CONCLUSIONS: Saliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.

Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 32422408  Clin Microbiol Infect. 2020 May 15;. doi: 10.1016/j.cmi・・・
著者: Eloise Williams, Katherine Bond, Bowen Zhang, Mark Putland, Deborah A Williamson
雑誌名: J Clin Microbiol. 2020 Jul 23;58(8). doi: 10.1128/JCM.00776-20. Epub 2020 Jul 23.
Abstract/Text
PMID 32317257  J Clin Microbiol. 2020 Jul 23;58(8). doi: 10.1128/JCM.0・・・
厚生労働省:唾液を用いたPCR検査に係る厚生労働科学研究の結果について「新型コロナウイルス感染症の診断における鼻かみ鼻汁及び唾液の有用性の検討」.
厚生労働省:第47回厚生科学審議会感染症部会 資料(令和2年9月25日)「新型コロナウイルス感染症の鼻腔拭い液を用いた検査について」 (厚生労働科学研究 研究者代表:りんくう総合医療センター感染症センター長 倭 正也).
著者: Nanshan Chen, Min Zhou, Xuan Dong, Jieming Qu, Fengyun Gong, Yang Han, Yang Qiu, Jingli Wang, Ying Liu, Yuan Wei, Jia'an Xia, Ting Yu, Xinxin Zhang, Li Zhang
雑誌名: Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
Abstract/Text BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.
METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.
FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.
INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.
FUNDING: National Key R&D Program of China.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32007143  Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0・・・
著者: Heshui Shi, Xiaoyu Han, Nanchuan Jiang, Yukun Cao, Osamah Alwalid, Jin Gu, Yanqing Fan, Chuansheng Zheng
雑誌名: Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.
Abstract/Text BACKGROUND: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course.
METHODS: Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups.
FINDINGS: 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4).
INTERPRETATION: COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1-3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia.
FUNDING: None.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32105637  Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016・・・
著者: Xingzhi Xie, Zheng Zhong, Wei Zhao, Chao Zheng, Fei Wang, Jun Liu
雑誌名: Radiology. 2020 Feb 12;:200343. doi: 10.1148/radiol.2020200343. Epub 2020 Feb 12.
Abstract/Text Some patients with positive chest CT findings may present with negative results of real time reverse-transcription-polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening.

PMID 32049601  Radiology. 2020 Feb 12;:200343. doi: 10.1148/radiol.202・・・
著者: Tao Ai, Zhenlu Yang, Hongyan Hou, Chenao Zhan, Chong Chen, Wenzhi Lv, Qian Tao, Ziyong Sun, Liming Xia
雑誌名: Radiology. 2020 Feb 26;:200642. doi: 10.1148/radiol.2020200642. Epub 2020 Feb 26.
Abstract/Text Background Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas.

PMID 32101510  Radiology. 2020 Feb 26;:200642. doi: 10.1148/radiol.202・・・
著者: Harrison X Bai, Ben Hsieh, Zeng Xiong, Kasey Halsey, Ji Whae Choi, Thi My Linh Tran, Ian Pan, Lin-Bo Shi, Dong-Cui Wang, Ji Mei, Xiao-Long Jiang, Qiu-Hua Zeng, Thomas K Egglin, Ping-Feng Hu, Saurabh Agarwal, Fangfang Xie, Sha Li, Terrance Healey, Michael K Atalay, Wei-Hua Liao
雑誌名: Radiology. 2020 Mar 10;:200823. doi: 10.1148/radiol.2020200823. Epub 2020 Mar 10.
Abstract/Text Background Despite its high sensitivity in diagnosing COVID-19 in a screening population, chest CT appearances of COVID 19 pneumonia are thought to be non-specific. Purpose To assess the performance of United States (U.S.) and Chinese radiologists in differentiating COVID-19 from viral pneumonia on chest CT. Methods A total of 219 patients with both positive COVID-19 by RT-PCR and abnormal chest CT findings were retrospectively identified from 7 Chinese hospitals in Hunan Providence, China from January 6 to February 20, 2020. A total of 205 patients with positive Respiratory Pathogen Panel for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia by original radiology interpretation within 7 days of each other were identified from Rhode Island Hospital in Providence, RI. Three Chinese radiologists blindly reviewed all chest CTs (n=424) to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched cases was randomly selected and evaluated by 4 U.S. radiologists in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CTs, three Chinese radiologists correctly differentiated COVID-19 from non-COVID-19 pneumonia 83% (350/424), 80% (338/424), and 60% (255/424) of the time, respectively. The seven radiologists had sensitivities of 80%, 67%, 97%, 93%, 83%, 73% and 70% and specificities of 100%, 93%, 7%, 100%, 93%, 93%, 100%. Compared to non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs. 57%, p<0.001), ground-glass opacity (91% vs. 68%, p<0.001), fine reticular opacity (56% vs. 22%, p<0.001), and vascular thickening (59% vs. 22%, p<0.001), but less likely to have a central+peripheral distribution (14.% vs. 35%, p<0.001), pleural effusion (4.1 vs. 39%, p<0.001) and lymphadenopathy (2.7% vs. 10.2%, p<0.001). Conclusion Radiologists in China and the United States distinguished COVID-19 from viral pneumonia on chest CT with high specificity but moderate sensitivity. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.

PMID 32155105  Radiology. 2020 Mar 10;:200823. doi: 10.1148/radiol.202・・・
著者: James M Sanders, Marguerite L Monogue, Tomasz Z Jodlowski, James B Cutrell
雑誌名: JAMA. 2020 Apr 13;. doi: 10.1001/jama.2020.6019. Epub 2020 Apr 13.
Abstract/Text Importance: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.
Observations: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
Conclusions and Relevance: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

PMID 32282022  JAMA. 2020 Apr 13;. doi: 10.1001/jama.2020.6019. Epub 2・・・
著者: Manli Wang, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong, Gengfu Xiao
雑誌名: Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4.
Abstract/Text
PMID 32020029  Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-0・・・
著者: Jonathan Grein, Norio Ohmagari, Daniel Shin, George Diaz, Erika Asperges, Antonella Castagna, Torsten Feldt, Gary Green, Margaret L Green, François-Xavier Lescure, Emanuele Nicastri, Rentaro Oda, Kikuo Yo, Eugenia Quiros-Roldan, Alex Studemeister, John Redinski, Seema Ahmed, Jorge Bernett, Daniel Chelliah, Danny Chen, Shingo Chihara, Stuart H Cohen, Jennifer Cunningham, Antonella D'Arminio Monforte, Saad Ismail, Hideaki Kato, Giuseppe Lapadula, Erwan L'Her, Toshitaka Maeno, Sumit Majumder, Marco Massari, Marta Mora-Rillo, Yoshikazu Mutoh, Duc Nguyen, Ewa Verweij, Alexander Zoufaly, Anu O Osinusi, Adam DeZure, Yang Zhao, Lijie Zhong, Anand Chokkalingam, Emon Elboudwarej, Laura Telep, Leighann Timbs, Ilana Henne, Scott Sellers, Huyen Cao, Susanna K Tan, Lucinda Winterbourne, Polly Desai, Robertino Mera, Anuj Gaggar, Robert P Myers, Diana M Brainard, Richard Childs, Timothy Flanigan
雑誌名: N Engl J Med. 2020 Apr 10;. doi: 10.1056/NEJMoa2007016. Epub 2020 Apr 10.
Abstract/Text BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.
METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.
RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.
CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Copyright © 2020 Massachusetts Medical Society.
PMID 32275812  N Engl J Med. 2020 Apr 10;. doi: 10.1056/NEJMoa2007016.・・・
著者: John H Beigel, Kay M Tomashek, Lori E Dodd, Aneesh K Mehta, Barry S Zingman, Andre C Kalil, Elizabeth Hohmann, Helen Y Chu, Annie Luetkemeyer, Susan Kline, Diego Lopez de Castilla, Robert W Finberg, Kerry Dierberg, Victor Tapson, Lanny Hsieh, Thomas F Patterson, Roger Paredes, Daniel A Sweeney, William R Short, Giota Touloumi, David Chien Lye, Norio Ohmagari, Myoung-Don Oh, Guillermo M Ruiz-Palacios, Thomas Benfield, Gerd Fätkenheuer, Mark G Kortepeter, Robert L Atmar, C Buddy Creech, Jens Lundgren, Abdel G Babiker, Sarah Pett, James D Neaton, Timothy H Burgess, Tyler Bonnett, Michelle Green, Mat Makowski, Anu Osinusi, Seema Nayak, H Clifford Lane, ACTT-1 Study Group Members
雑誌名: N Engl J Med. 2020 Oct 8;. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.
Abstract/Text BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.
METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).
CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Copyright © 2020 Massachusetts Medical Society.
PMID 32445440  N Engl J Med. 2020 Oct 8;. doi: 10.1056/NEJMoa2007764. ・・・
著者: Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult
雑誌名: Int J Antimicrob Agents. 2020 Mar 20;:105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
Abstract/Text BACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads.
PATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
RESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
CONCLUSION: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Copyright © 2020. Published by Elsevier B.V.
PMID 32205204  Int J Antimicrob Agents. 2020 Mar 20;:105949. doi: 10.1・・・
著者: Andre C Kalil
雑誌名: JAMA. 2020 Mar 24;. doi: 10.1001/jama.2020.4742. Epub 2020 Mar 24.
Abstract/Text
PMID 32208486  JAMA. 2020 Mar 24;. doi: 10.1001/jama.2020.4742. Epub 2・・・
Chloroquine [database online. Hudson, OH: Lexicomp Inc; 2016. Accessed March 17, 2020.].
著者: Nelson Lee, K C Allen Chan, David S Hui, Enders K O Ng, Alan Wu, Rossa W K Chiu, Vincent W S Wong, Paul K S Chan, K T Wong, Eric Wong, C S Cockram, John S Tam, Joseph J Y Sung, Y M Dennis Lo
雑誌名: J Clin Virol. 2004 Dec;31(4):304-9. doi: 10.1016/j.jcv.2004.07.006.
Abstract/Text BACKGROUND: The effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown.
OBJECTIVE: To compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo.
STUDY DESIGN: Serial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene.
RESULTS: Among 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days), respectively.
CONCLUSION: Our findings suggested "early" corticosteroid treatment was associated with a higher subsequent plasma viral load.

PMID 15494274  J Clin Virol. 2004 Dec;31(4):304-9. doi: 10.1016/j.jcv.・・・
著者: Yaseen M Arabi, Yasser Mandourah, Fahad Al-Hameed, Anees A Sindi, Ghaleb A Almekhlafi, Mohamed A Hussein, Jesna Jose, Ruxandra Pinto, Awad Al-Omari, Ayman Kharaba, Abdullah Almotairi, Kasim Al Khatib, Basem Alraddadi, Sarah Shalhoub, Ahmed Abdulmomen, Ismael Qushmaq, Ahmed Mady, Othman Solaiman, Abdulsalam M Al-Aithan, Rajaa Al-Raddadi, Ahmed Ragab, Hanan H Balkhy, Abdulrahman Al Harthy, Ahmad M Deeb, Hanan Al Mutairi, Abdulaziz Al-Dawood, Laura Merson, Frederick G Hayden, Robert A Fowler, Saudi Critical Care Trial Group
雑誌名: Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767. doi: 10.1164/rccm.201706-1172OC.
Abstract/Text RATIONALE: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation.
OBJECTIVES: To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS.
METHODS: ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders.
MEASUREMENTS AND MAIN RESULTS: Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005).
CONCLUSIONS: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

PMID 29161116  Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767. ・・・
著者: RECOVERY Collaborative Group, Peter Horby, Wei Shen Lim, Jonathan R Emberson, Marion Mafham, Jennifer L Bell, Louise Linsell, Natalie Staplin, Christopher Brightling, Andrew Ustianowski, Einas Elmahi, Benjamin Prudon, Christopher Green, Timothy Felton, David Chadwick, Kanchan Rege, Christopher Fegan, Lucy C Chappell, Saul N Faust, Thomas Jaki, Katie Jeffery, Alan Montgomery, Kathryn Rowan, Edmund Juszczak, J Kenneth Baillie, Richard Haynes, Martin J Landray
雑誌名: N Engl J Med. 2020 Jul 17;. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17.
Abstract/Text BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.
METHODS: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison.
RESULTS: A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
CONCLUSIONS: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.).

Copyright © 2020 Massachusetts Medical Society.
PMID 32678530  N Engl J Med. 2020 Jul 17;. doi: 10.1056/NEJMoa2021436.・・・
著者: Xiaoling Xu, Mingfeng Han, Tiantian Li, Wei Sun, Dongsheng Wang, Binqing Fu, Yonggang Zhou, Xiaohu Zheng, Yun Yang, Xiuyong Li, Xiaohua Zhang, Aijun Pan, Haiming Wei
雑誌名: Proc Natl Acad Sci U S A. 2020 Apr 29;. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29.
Abstract/Text After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Copyright © 2020 the Author(s). Published by PNAS.
PMID 32350134  Proc Natl Acad Sci U S A. 2020 Apr 29;. doi: 10.1073/pn・・・
著者: Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Roberto Tonelli, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Luca Corradi, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Massimo Girardis, Sara Tedeschi, Maddalena Giannella, Michele Bartoletti, Renato Pascale, Giovanni Dolci, Lucio Brugioni, Antonello Pietrangelo, Andrea Cossarizza, Federico Pea, Enrico Clini, Carlo Salvarani, Marco Massari, Pier Luigi Viale, Cristina Mussini
雑誌名: Lancet Rheumatol. 2020 Aug;2(8):e474-e484. doi: 10.1016/S2665-9913(20)30173-9. Epub 2020 Jun 24.
Abstract/Text Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment.
Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score.
Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40-0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001).
Interpretation: Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.
Funding: None.

© 2020 Elsevier Ltd. All rights reserved.
PMID 32835257  Lancet Rheumatol. 2020 Aug;2(8):e474-e484. doi: 10.1016・・・
著者: Vanessa Piechotta, Khai Li Chai, Sarah J Valk, Carolyn Doree, Ina Monsef, Erica M Wood, Abigail Lamikanra, Catherine Kimber, Zoe McQuilten, Cynthia So-Osman, Lise J Estcourt, Nicole Skoetz
雑誌名: Cochrane Database Syst Rev. 2020 Jul 10;7:CD013600. doi: 10.1002/14651858.CD013600.pub2. Epub 2020 Jul 10.
Abstract/Text BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.  OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19.
SEARCH METHODS: We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 4 June 2020.
SELECTION CRITERIA: We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs.  MAIN RESULTS: This is the first living update of our review. We included 20 studies (1 RCT, 3 controlled NRSIs, 16 non-controlled NRSIs) with 5443 participants, of whom 5211 received convalescent plasma, and identified a further 98 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 50 are randomised. We did not identify any completed studies evaluating hyperimmune immunoglobulin. Overall risk of bias of included studies was high, due to study design, type of participants, and other previous or concurrent treatments. Effectiveness of convalescent plasma for people with COVID-19  We included results from four controlled studies (1 RCT (stopped early) with 103 participants, of whom 52 received convalescent plasma; and 3 controlled NRSIs with 236 participants, of whom 55 received convalescent plasma) to assess effectiveness of convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. All-cause mortality at hospital discharge (1 controlled NRSI, 21 participants) We are very uncertain whether convalescent plasma has any effect on all-cause mortality at hospital discharge (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.61 to 1.31; very low-certainty evidence). Time to death (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma prolongs time to death (RCT: hazard ratio (HR) 0.74, 95% CI 0.30 to 1.82; controlled NRSI: HR 0.46, 95% CI 0.22 to 0.96; very low-certainty evidence). Improvement of clinical symptoms, assessed by need for respiratory support (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma has any effect on improvement of clinical symptoms at seven days (RCT: RR 0.98, 95% CI 0.30 to 3.19), 14 days (RCT: RR 1.85, 95% CI 0.91 to 3.77; controlled NRSI: RR 1.08, 95% CI 0.91 to 1.29), and 28 days (RCT: RR 1.20, 95% CI 0.80 to 1.81; very low-certainty evidence). Quality of life No studies reported this outcome.  Safety of convalescent plasma for people with COVID-19 We included results from 1 RCT, 3 controlled NRSIs and 10 non-controlled NRSIs assessing safety of convalescent plasma. Reporting of adverse events and serious adverse events was variable. The controlled studies reported on adverse events and serious adverse events only in participants receiving convalescent plasma. The duration of follow-up varied. Some, but not all, studies included death as a serious adverse event.  Grade 3 or 4 adverse events (13 studies, 201 participants) The studies did not report the grade of adverse events. Thirteen studies (201 participants) reported on adverse events of possible grade 3 or 4 severity. The majority of these adverse events were allergic or respiratory events. We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence).  Serious adverse events (14 studies, 5201 participants)  Fourteen studies (5201 participants) reported on serious adverse events. The majority of participants were from one non-controlled NRSI (5000 participants), which reported only on serious adverse events limited to the first four hours after convalescent plasma transfusion. This study included death as a serious adverse event; they reported 15 deaths, four of which they classified as potentially, probably or definitely related to transfusion. Other serious adverse events reported in all studies were predominantly allergic or respiratory in nature, including anaphylaxis, transfusion-associated dyspnoea, and transfusion-related acute lung injury (TRALI). We are very uncertain whether or not convalescent plasma affects the number of serious adverse events.
AUTHORS' CONCLUSIONS: We are very uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. For safety outcomes we also included non-controlled NRSIs. There was limited information regarding adverse events. Of the controlled studies, none reported on this outcome in the control group. There is only very low-certainty evidence for safety of convalescent plasma for COVID-19.  While major efforts to conduct research on COVID-19 are being made, problems with recruiting the anticipated number of participants into these studies are conceivable. The early termination of the first RCT investigating convalescent plasma, and the multitude of studies registered in the past months illustrate this. It is therefore necessary to critically assess the design of these registered studies, and well-designed studies should be prioritised. Other considerations for these studies are the need to report outcomes for all study arms in the same way, and the importance of maintaining comparability in terms of co-interventions administered in all study arms.  There are 98 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 50 are RCTs. This is the first living update of the review, and we will continue to update this review periodically. These updates may show different results to those reported here.

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PMID 32648959  Cochrane Database Syst Rev. 2020 Jul 10;7:CD013600. doi・・・
著者: Ling Li, Wei Zhang, Yu Hu, Xunliang Tong, Shangen Zheng, Juntao Yang, Yujie Kong, Lili Ren, Qing Wei, Heng Mei, Caiying Hu, Cuihua Tao, Ru Yang, Jue Wang, Yongpei Yu, Yong Guo, Xiaoxiong Wu, Zhihua Xu, Li Zeng, Nian Xiong, Lifeng Chen, Juan Wang, Ning Man, Yu Liu, Haixia Xu, E Deng, Xuejun Zhang, Chenyue Li, Conghui Wang, Shisheng Su, Linqi Zhang, Jianwei Wang, Yanyun Wu, Zhong Liu
雑誌名: JAMA. 2020 Aug 4;324(5):460-470. doi: 10.1001/jama.2020.10044.
Abstract/Text Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.
Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.
Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.
Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.
Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.
Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.
Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.
Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

PMID 32492084  JAMA. 2020 Aug 4;324(5):460-470. doi: 10.1001/jama.2020・・・
著者: F A Klok, M J H A Kruip, N J M van der Meer, M S Arbous, D A M P J Gommers, K M Kant, F H J Kaptein, J van Paassen, M A M Stals, M V Huisman, H Endeman
雑誌名: Thromb Res. 2020 Apr 10;. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10.
Abstract/Text INTRODUCTION: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available.
METHODS: We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.
RESULTS: We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.
CONCLUSION: The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Copyright © 2020. Published by Elsevier Ltd.
PMID 32291094  Thromb Res. 2020 Apr 10;. doi: 10.1016/j.thromres.2020.・・・
著者: R J Smith, R G Bryant
雑誌名: Biochem Biophys Res Commun. 1975 Oct 27;66(4):1281-6. doi: 10.1016/0006-291x(75)90498-2.
Abstract/Text
PMID 3  Biochem Biophys Res Commun. 1975 Oct 27;66(4):1281-6. d・・・
著者: Denis Y Logunov, Inna V Dolzhikova, Olga V Zubkova, Amir I Tukhvatullin, Dmitry V Shcheblyakov, Alina S Dzharullaeva, Daria M Grousova, Alina S Erokhova, Anna V Kovyrshina, Andrei G Botikov, Fatima M Izhaeva, Olga Popova, Tatiana A Ozharovskaya, Ilias B Esmagambetov, Irina A Favorskaya, Denis I Zrelkin, Daria V Voronina, Dmitry N Shcherbinin, Alexander S Semikhin, Yana V Simakova, Elizaveta A Tokarskaya, Nadezhda L Lubenets, Daria A Egorova, Maksim M Shmarov, Natalia A Nikitenko, Lola F Morozova, Elena A Smolyarchuk, Evgeny V Kryukov, Vladimir F Babira, Sergei V Borisevich, Boris S Naroditsky, Alexander L Gintsburg
雑誌名: Lancet. 2020 Sep 26;396(10255):887-897. doi: 10.1016/S0140-6736(20)31866-3. Epub 2020 Sep 4.
Abstract/Text BACKGROUND: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.
METHODS: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18-60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875.
FINDINGS: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation.
INTERPRETATION: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19.
FUNDING: Ministry of Health of the Russian Federation.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32896291  Lancet. 2020 Sep 26;396(10255):887-897. doi: 10.1016/S0・・・
著者: Angelo Carfì, Roberto Bernabei, Francesco Landi, Gemelli Against COVID-19 Post-Acute Care Study Group
雑誌名: JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
Abstract/Text
PMID 32644129  JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.202・・・
著者: J P Metlay, M J Fine, R Schulz, T J Marrie, C M Coley, W N Kapoor, D E Singer
雑誌名: J Gen Intern Med. 1997 Jul;12(7):423-30. doi: 10.1046/j.1525-1497.1997.00074.x.
Abstract/Text OBJECTIVE: To determine the rates of resolution of symptoms and return to premorbid health status and assess the association of these outcomes with health care utilization in patients with community-acquired pneumonia.
DESIGN: A prospective, multicenter cohort study.
SETTING: Inpatient and outpatient facilities at three university hospitals, one community hospital, and one staff-model health maintenance organization.
PATIENTS: Five hundred seventy-six adults (aged > or = 18 years) with clinical and radiographic evidence of pneumonia, judged by a validated pneumonia severity index to be at low risk of dying.
MEASUREMENTS AND MAIN RESULTS: The presence and severity of five symptoms (cough, fatigue, dyspnea, sputum, and chest pain) were recorded through questionnaires administered at four time points: 0, 7, 30, and 90 days from the time of radiographic diagnosis of pneumonia. A summary symptom score was tabulated as the sum of the five individual severity scores. Patients also provided responses to the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and reported the number of and reason for outpatient physician visits. Symptoms and health status 30 days before pneumonia onset (prepneumonia) were obtained at the initial interview. All symptoms, except pleuritic chest pain, were still commonly reported at 30 days, and the prevalence of each symptom at 90 days was still nearly twice prepneumonia levels. Physical health measures derived from the SF-36 Form declined significantly at presentation but continued to improve over all three follow-up time periods. Patients with elevated symptom scores at day 7 or day 30 were significantly more likely to report pneumonia-related ambulatory care visits at the subsequent day 30 or day 90 interviews, respectively.
CONCLUSIONS: Disease-specific symptom resolution and recovery of the premorbid physical health status requires more than 30 days for many patients with pneumonia. Delayed resolution of symptoms is associated with increased utilization of outpatient physician visits.

PMID 9229281  J Gen Intern Med. 1997 Jul;12(7):423-30. doi: 10.1046/j・・・
著者: Yuhui Wang, Chengjun Dong, Yue Hu, Chungao Li, Qianqian Ren, Xin Zhang, Heshui Shi, Min Zhou
雑誌名: Radiology. 2020 Aug;296(2):E55-E64. doi: 10.1148/radiol.2020200843. Epub 2020 Mar 19.
Abstract/Text Background CT may play a central role in the diagnosis and management of coronavirus disease 2019 (COVID-19) pneumonia. Purpose To perform a longitudinal study to analyze the serial CT findings over time in patients with COVID-19 pneumonia. Materials and Methods During January 16 to February 17, 2020, 90 patients (33 men, 57 women; mean age, 45 years) with COVID-19 pneumonia were prospectively enrolled and followed up until being discharged, death, or the end of the study. A total of 366 CT scans were acquired and reviewed by two groups of radiologists for the patterns and distribution of lung abnormalities, total CT scores, and number of zones involved. Those features were analyzed for temporal change. Results CT scores and number of zones involved progressed rapidly, peaked during illness days 6-11 (median CT score, 5; median number of zones involved, five), and were followed by persistence of high levels. The predominant pattern of abnormalities after symptom onset was ground-glass opacity (35 of 78 scans [45%] to 49 of 79 scans [62%] in different periods). The percentage of mixed pattern peaked on illness days 12-17 (30 of 78 scans [38%]) and became the second most predominant pattern thereafter. Pure ground-glass opacity was the most prevalent subtype of ground-glass opacity after symptom onset (20 of 50 scans [40%] to 20 of 28 scans [71%]). The percentage of ground-glass opacity with irregular linear opacity peaked on illness days 6-11 (14 of 50 scans [28%]) and became the second most prevalent subtype thereafter. The distribution of lesions was predominantly bilateral and subpleural. Sixty-six of the 70 patients discharged (94%) had residual disease on final CT scans (median CT score, 4; median number of zones involved, four), with ground-glass opacity (42 of 70 patients [60%]) and pure ground-glass opacity (31 of 42 patients [74%]) the most common pattern and subtype. Conclusion The extent of lung abnormalities at CT peaked during illness days 6-11. The temporal changes of the diverse CT manifestations followed a specific pattern, which might indicate the progression and recovery of the illness. © RSNA, 2020 Online supplemental material is available for this article.

PMID 32191587  Radiology. 2020 Aug;296(2):E55-E64. doi: 10.1148/radiol・・・
著者: Samir Nusair
雑誌名: Eur Respir J. 2020 Jul;56(1). doi: 10.1183/13993003.01832-2020. Epub 2020 Jul 23.
Abstract/Text
PMID 32703822  Eur Respir J. 2020 Jul;56(1). doi: 10.1183/13993003.018・・・
著者: Wenhua Liang, Weijie Guan, Ruchong Chen, Wei Wang, Jianfu Li, Ke Xu, Caichen Li, Qing Ai, Weixiang Lu, Hengrui Liang, Shiyue Li, Jianxing He
雑誌名: Lancet Oncol. 2020 Mar;21(3):335-337. doi: 10.1016/S1470-2045(20)30096-6. Epub 2020 Feb 14.
Abstract/Text
PMID 32066541  Lancet Oncol. 2020 Mar;21(3):335-337. doi: 10.1016/S147・・・
著者: Yang Xia, Rui Jin, Jing Zhao, Wen Li, Huahao Shen
雑誌名: Lancet Oncol. 2020 Apr;21(4):e180. doi: 10.1016/S1470-2045(20)30150-9. Epub 2020 Mar 3.
Abstract/Text
PMID 32142622  Lancet Oncol. 2020 Apr;21(4):e180. doi: 10.1016/S1470-2・・・
著者: Vikas Mehta, Sanjay Goel, Rafi Kabarriti, Daniel Cole, Mendel Goldfinger, Ana Acuna-Villaorduna, Kith Pradhan, Raja Thota, Stan Reissman, Joseph A Sparano, Benjamin A Gartrell, Richard V Smith, Nitin Ohri, Madhur Garg, Andrew D Racine, Shalom Kalnicki, Roman Perez-Soler, Balazs Halmos, Amit Verma
雑誌名: Cancer Discov. 2020 Jul;10(7):935-941. doi: 10.1158/2159-8290.CD-20-0516. Epub 2020 May 1.
Abstract/Text Patients with cancer are presumed to be at increased risk from COVID-19 infection-related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19-positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. SIGNIFICANCE: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.This article is highlighted in the In This Issue feature, p. 890.

©2020 American Association for Cancer Research.
PMID 32357994  Cancer Discov. 2020 Jul;10(7):935-941. doi: 10.1158/215・・・
著者: Masumi Ueda, Renato Martins, Paul C Hendrie, Terry McDonnell, Jennie R Crews, Tracy L Wong, Brittany McCreery, Barbara Jagels, Aaron Crane, David R Byrd, Steven A Pergam, Nancy E Davidson, Catherine Liu, F Marc Stewart
雑誌名: J Natl Compr Canc Netw. 2020 Mar 20;:1-4. doi: 10.6004/jnccn.2020.7560. Epub 2020 Mar 20.
Abstract/Text The first confirmed case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020, in Snohomish County, Washington. At the epicenter of COVID-19 in the United States, the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, and University of Washington are at the forefront of delivering care to patients with cancer during this public health crisis. This Special Feature highlights the unique circumstances and challenges of cancer treatment amidst this global pandemic, and the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.

PMID 32197238  J Natl Compr Canc Netw. 2020 Mar 20;:1-4. doi: 10.6004/・・・
著者: Anna S Berghoff, Margaretha Gansterer, Arne C Bathke, Wolfgang Trutschnig, Philipp Hungerländer, Julia M Berger, Judith Kreminger, Angelika M Starzer, Robert Strassl, Ralf Schmidt, Harald Willschke, Wolfgang Lamm, Markus Raderer, Alex D Gottlieb, Norbert J Mauser, Matthias Preusser
雑誌名: J Clin Oncol. 2020 Oct 20;38(30):3547-3554. doi: 10.1200/JCO.20.01442. Epub 2020 Aug 14.
Abstract/Text PURPOSE: To analyze the prevalence of SARS-CoV-2 infection in patients with cancer in hospital care after implementation of institutional and governmental safety measurements.
METHODS: Patients with cancer routinely tested for SARS-CoV-2 RNA by nasal swab and real-time polymerase chain reaction between March 21 and May 4, 2020, were included. The results of this cancer cohort were statistically compared with the SARS-CoV-2 prevalence in the Austrian population as determined by a representative nationwide random sample study (control cohort 1) and a cohort of patients without cancer presenting to our hospital (control cohort 2).
RESULTS: A total of 1,688 SARS-CoV-2 tests in 1,016 consecutive patients with cancer were performed. A total of 270 of 1,016 (26.6%) of the patients were undergoing active anticancer treatment in a neoadjuvant/adjuvant and 560 of 1,016 (55.1%) in a palliative setting. A total of 53 of 1,016 (5.2%) patients self-reported symptoms potentially associated with COVID-19. In 4 of 1,016 (0.4%) patients, SARS-CoV-2 was detected. At the time of testing at our department, all four SARS-CoV-2-positive patients were asymptomatic, and two of them had recovered from symptomatic COVID-19. Viral clearance was achieved in three of the four patients 14-56 days after testing positive. The estimated odds ratio of SARS-CoV-2 prevalence between the cancer cohort and control cohort 1 was 1.013 (95% CI, 0.209 to 4.272; P = 1), and between control cohort 2 and the cancer cohort it was 18.333 (95% CI, 6.056 to 74.157).
CONCLUSION: Our data indicate that continuation of active anticancer therapy and follow-up visits in a large tertiary care hospital are feasible and safe after implementation of strict population-wide and institutional safety measures during the current COVID-19 pandemic. Routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.

PMID 32795227  J Clin Oncol. 2020 Oct 20;38(30):3547-3554. doi: 10.120・・・
著者: Savannah Karmen-Tuohy, Philip M Carlucci, Fainareti N Zervou, Ioannis M Zacharioudakis, Gabriel Rebick, Elizabeth Klein, Jenna Reich, Simon Jones, Joseph Rahimian
雑誌名: J Acquir Immune Defic Syndr. 2020 Sep 1;85(1):6-10. doi: 10.1097/QAI.0000000000002423.
Abstract/Text BACKGROUND: SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection.
METHODS: Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020, and April 23, 2020, we matched 21 HIV-positive patients with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups.
RESULTS: Although there was a trend toward increased rates of intensive care unit admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups.
CONCLUSIONS: This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.

PMID 32568770  J Acquir Immune Defic Syndr. 2020 Sep 1;85(1):6-10. doi・・・
著者: Joni Gilissen, Lara Pivodic, Kathleen T Unroe, Lieve Van den Block
雑誌名: J Pain Symptom Manage. 2020 Aug;60(2):e56-e69. doi: 10.1016/j.jpainsymman.2020.04.151. Epub 2020 May 11.
Abstract/Text COVID-19 mortality disproportionally affects nursing homes, creating enormous pressures to deliver high-quality end-of-life care. Comprehensive palliative care should be an explicit part of both national and global COVID-19 response plans. Therefore, we aimed to identify, review, and compare national and international COVID-19 guidance for nursing homes concerning palliative care, issued by government bodies and professional associations. We performed a directed documentary and content analysis of newly developed or adapted COVID-19 guidance documents from across the world. Documents were collected via expert consultation and independently screened against prespecified eligibility criteria. We applied thematic analysis and narrative synthesis techniques. We identified 21 eligible documents covering both nursing homes and palliative care, from the World Health Organization (n = 3), and eight individual countries: U.S. (n = 7), The Netherlands (n = 2), Ireland (n = 1), U.K. (n = 3), Switzerland (n = 3), New Zealand (n = 1), and Belgium (n = 1). International documents focused primarily on infection prevention and control, including only a few sentences on palliative care-related topics. Palliative care themes most frequently mentioned across documents were end-of-life visits, advance care planning documentation, and clinical decision making toward the end of life (focusing on hospital transfers). There is a dearth of comprehensive international COVID-19 guidance on palliative care for nursing homes. Most have a limited focus both regarding breadth of topics and recommendations made. Key aspects of palliative care, that is, symptom management, staff education and support, referral to specialist services or hospice, and family support, need greater attention in future guidelines.

Copyright © 2020 American Academy of Hospice and Palliative Medicine. All rights reserved.
PMID 32437942  J Pain Symptom Manage. 2020 Aug;60(2):e56-e69. doi: 10.・・・

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