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      Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

      research-article
      1 , 2 , 3 , 4 , 5 , 1 , 2 , 6 , 7 , 1 , 2 , 8 , 9 , 10 , 11 , 12 , 13 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 1 , 22 , 16 , 17 , 23 , 24 , 10 , 25 , 8 , 26 , 2 , 27 , 28 , 29 , 30 , 31 , 1 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ,
      Intensive Care Medicine
      Springer Berlin Heidelberg
      Coronavirus, COVID-19, SARS CoV-2, Clinical practice guidelines, Critical illness

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          Abstract

          Background

          The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

          Methods

          We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.

          Results

          The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.

          Conclusion

          The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

          Electronic supplementary material

          The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.

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          Most cited references141

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

          Summary 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.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                https://guidecanada.org/
                andrewrhodes@nhs.net
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                28 March 2020
                : 1-34
                Affiliations
                [1 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Department of Medicine, , McMaster University, ; Hamilton, Canada
                [2 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Department of Health Research Methods, Evidence, and Impact, , McMaster University, ; Hamilton, Canada
                [3 ]GRID grid.475435.4, Department of Intensive Care, , Copenhagen University Hospital Rigshospitalet, ; 4131 Copenhagen, Denmark
                [4 ]Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI), Copenhagen, Denmark
                [5 ]GRID grid.452607.2, ISNI 0000 0004 0580 0891, Intensive Care Department, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, , King Abdullah International Medical Research Center, ; Riyadh, Kingdom of Saudi Arabia
                [6 ]GRID grid.251993.5, ISNI 0000000121791997, Division of Critical Care Medicine, Division of Pulmonary Medicine, Department of Medicine, , Montefiore Healthcare System/Albert Einstein College of Medicine, ; Bronx, NY USA
                [7 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Interdepartmental Division of Critical Care Medicine, Institute of Health Policy, Management and Evaluation, , University of Toronto, ; Toronto, Canada
                [8 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Warren Alpert School of Medicine, , Brown University, ; Providence, RI USA
                [9 ]GRID grid.240588.3, ISNI 0000 0001 0557 9478, Rhode Island Hospital, ; Providence, RI USA
                [10 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Intensive Care Medicine, University Medical Center Utrecht, , Utrecht University, ; Utrecht, The Netherlands
                [11 ]GRID grid.7692.a, ISNI 0000000090126352, Julius Center for Health Sciences and Primary Care, ; Utrecht, The Netherlands
                [12 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Pharmacy, NewYork-Presbyterian Hospital, , Columbia University Irving Medical Center, ; New York, NY USA
                [13 ]GRID grid.413106.1, ISNI 0000 0000 9889 6335, Medical ICU, , Peking Union Medical College Hospital, ; 1 Shuai Fu Yuan, Beijing, 100730 China
                [14 ]GRID grid.413104.3, ISNI 0000 0000 9743 1587, Department of Critical Care Medicine, , Sunnybrook Health Sciences Centre, ; Toronto, ON Canada
                [15 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Anesthesia and Interdepartmental Division of Critical Care Medicine, , University of Toronto, ; Toronto, ON Canada
                [16 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Department of Anesthesia and Intensive Care, , Humanitas Clinical and Research Center, ; Rozzano, Milan, Italy
                [17 ]GRID grid.452490.e, Department of Biomedical Science, , Humanitas University, ; Pieve Emanuele, Milan, Italy
                [18 ]GRID grid.267370.7, ISNI 0000 0004 0533 4667, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, , University of Ulsan College of Medicine, ; Seoul, Korea
                [19 ]GRID grid.419681.3, ISNI 0000 0001 2164 9667, Critical Care Medicine Department, National Institutes of Health Clinical Center and Laboratory of Immunoregulation, , National Institute of Allergy and Infectious Diseases, ; Baltimore, USA
                [20 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Faculty of Medicine, , Imperial College, ; London, UK
                [21 ]GRID grid.43519.3a, ISNI 0000 0001 2193 6666, Department of Internal Medicine, College of Medicine and Health Sciences, , United Arab Emirates University, ; PO Box 17666, Al Ain, United Arab Emirates
                [22 ]GRID grid.415102.3, ISNI 0000 0004 0545 1978, Population Health Research Institute, ; Hamilton, Canada
                [23 ]GRID grid.451349.e, Microbiology and Infection Control, , St George’s University Hospitals NHS Foundation Trust & St George’s University of London, ; London, UK
                [24 ]GRID grid.412162.2, ISNI 0000 0004 0441 5844, Emory University Hospital, ; Atlanta, USA
                [25 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Division of Infectious Diseases, , University of Toronto, ; Toronto, Canada
                [26 ]GRID grid.273335.3, ISNI 0000 0004 1936 9887, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, , State University of New York at Buffalo, ; Buffalo, USA
                [27 ]GUIDE Research Methods Group, Hamilton, Canada
                [28 ]GRID grid.39382.33, ISNI 0000 0001 2160 926X, Houston Children’s Hospital, , Baylor College of Medicine, ; Houston, USA
                [29 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Department of Anesthesia, , McMaster University, ; Hamilton, Canada
                [30 ]GRID grid.7563.7, ISNI 0000 0001 2174 1754, Department of Medicine and Surgery, , Milano-Bicocca University, ; Milan, Italy
                [31 ]GRID grid.415025.7, ISNI 0000 0004 1756 8604, ASST-Monza, Desio and San Gerardo Hospital, ; Monza, Italy
                [32 ]GRID grid.415254.3, ISNI 0000 0004 1790 7311, Department of Emergency Medicine, , King Abdulaziz Medical City, ; Riyadh, Saudi Arabia
                [33 ]GRID grid.415696.9, Director, Research and Innovation Centre, King Saud Medical City, , Ministry of Health, ; Riyadh, Kingdom of Saudi Arabia
                [34 ]GRID grid.415508.d, ISNI 0000 0001 1964 6010, Critical Care Division, , The George Institute for Global Health and UNSW, ; Sydney, Australia
                [35 ]GRID grid.412703.3, ISNI 0000 0004 0587 9093, Malcolm Fisher Department of Intensive Care, , Royal North Shore Hospital, ; Sydney, Australia
                [36 ]GRID grid.27755.32, ISNI 0000 0000 9136 933X, Division of Infectious Diseases and International Health, Department of Medicine, , University, of Virginia, School of Medicine, ; Charlottesville, VA USA
                [37 ]GRID grid.34477.33, ISNI 0000000122986657, Division of Pulmonary, Critical Care, and Sleep Medicine, , University of Washington, ; Seattle, USA
                [38 ]GRID grid.451349.e, Adult Critical Care, , St George’s University Hospitals NHS Foundation Trust & St George’s University of London, ; London, UK
                Author information
                https://orcid.org/0000-0003-0343-3234
                Article
                6022
                10.1007/s00134-020-06022-5
                7101866
                32222812
                e514bec2-f290-4e3e-882a-caec92f7cabb
                © European Society of Intensive Care Medicine and the Society of Critical Care Medicine 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 15 March 2020
                : 20 March 2020
                Categories
                Guidelines

                Emergency medicine & Trauma
                coronavirus,covid-19,sars cov-2,clinical practice guidelines,critical illness

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