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      Critical care crisis and some recommendations during the COVID-19 epidemic in China

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          Abstract

          Since December 2019, a severe acute respiratory infection (SARI) caused by 2019 novel coronavirus (SARS-CoV-2), began to spread from Wuhan to all of China [1, 2], and indeed the world. As of Feb 10, 2020, there are more than 40,000 confirmed cases and > 1000 deaths in China. Lack of critical care resource in face of COVID-19 epidemics Based on data reported by the National Health Commission of China, there have been about 2000 new confirmed cases and > 4000 suspected cases daily over the past week in Wuhan [3]. About 15% of the patients have developed severe pneumonia, and about 6% need noninvasive or invasive ventilatory support. Currently, there are about 1000 patients who need ventilatory support and another 120 new patients daily who require noninvasive or invasive ventilation support in Wuhan city; however, there are only about 600 ICU beds [4]. To address this shortfall, 70 ICU beds were created from general beds and the government quickly transformed three general hospitals to critical care hospitals with a total of about 2500 beds that specialize in patients with severe SARS-CoV-2 pneumonia (equipped with monitors and high-flow nasal cannula, noninvasive ventilator or invasive ventilators). An equally great (or potentially greater) problem is the shortage of trained personnel to treat these critically ill patients. Until the crisis, there were about 300 ICU physicians and 1000 ICU nurses in Wuhan city. By the end of January, more than 600 additional ICU doctors and 1500 ICU nurses were transferred to Wuhan from the rest of China. As well, an additional 3000 staff including infectious disease, respiratory, internal medicine physicians and nurses were transferred to Wuhan by the government. There are logistical issues which make care of the patients difficult. These include donning of personal protective equipment (e.g., gloves, gowns, respiratory and eye protection), lack of instruments and disposables, and shortages of supplemental oxygen. Many severe hypoxemic patients only receive high-flow nasal oxygen (HFNO) or noninvasive mechanical ventilation rather than invasive mechanical ventilation because of intubation delay or lack of mechanical ventilators (especially at early phase). Our preliminary data show that only about 25% of patients who died were intubated and received mechanical ventilation. Recommendations It’s not possible at this stage to create new equipment or personnel. However, it would be very helpful to have mathematical models developed which predict the expected number of patients, and the necessary resources (equipment and personnel) required to treat these patients. This would aid in determining what resources might be moved to Wuhan to help local health care personnel. Challenge of early recognition and treatment of critical SARI patients Several previous reports have described the characteristics of SARS-CoV-2 infected patients [2, 5, 6]. Most patients are > 50 years of age; the mean age is much older than patients infected with H1N1 or with Middle East respiratory syndrome (MERS) [7–9]. About 30 to 50% of COVID-19 patients have chronic comorbidities. The duration from the initial symptom to respiratory failure in most patients is > 7 days, which is longer than H1N1 [7, 8]. Additionally, many patients that go on to develop respiratory failure had hypoxemia but without signs of respiratory distress, especially in the elderly patients (“silent hypoxemia”). Moreover, only a very small proportion of patients have other organ dysfunction (e.g., shock, acute kidney injury) prior to developing respiratory failure. These characteristics suggest that traditional methods such as quick sequential organ failure assessment (qSOFA) score and the new early warning score (NEWS) may not help predict those patients who will go on to develop respiratory failure. Therefore, it is urgent to establish a prediction or early recognition model of patients likely to fail. Although the novel coronavirus was quickly isolated and sequenced [10], there are no proven, effective drugs to treat COVID-19. Based on in vitro screening studies, several drugs were found to inhibit the virus [11]. One case report demonstrated a surprising effect of remdesivir for SARS-CoV-2 infection [12]; however, the clinical impact remains unclear. Encouragingly, several clinical trials are undergoing (ChiCTR2000029308, NCT04252664 and NCT04257656) to determine the effect of lopinavir/ritonavir or remdesivir. We have also tried Traditional Chinese Medicine such as Xuebijing, and several clinical trials are ongoing in this regard. Recommendations Identifying a biomarker(s) that predicts severity and outcome in COVID-19 patients early in the presentation would be extremely helpful. Our data (unpublished) demonstrate that severe lymphopenia and high levels of C-reactive protein correlated with the severity of hypoxemia and predicted hospital mortality. In addition, the change of lymphocyte counts during the first 4 days after hospital admission was highly associated with mortality. Crisis in management of SARI in the ICU The mortality rate of SARI is highest (4%) in Wuhan city, followed by other cities in Hubei province (1.4%) and other provinces (0.25%) [3]. The higher morality in Wuhan may due to the limited resources, but we are uncertain whether patients are sicker in Wuhan than in other cities. Understanding the characteristics of the dead patients would help in triaging patients and allocating resources. We analyzed data of 135 patients who died before Jan 30, 2019, in Wuhan city. Older age and male were common in non-surviving patients. More than 70% patients had one or more comorbidities. Hypertension (48.2%) was the most common comorbidity in non-surviving patients, followed by diabetes (26.7%) and ischemic heart disease (17.0%), similar to data reported by others [5, 6]. Importantly, as stated above, of the patients who died only ~ 25% received invasive mechanical ventilation or ECMO. The median duration of HFNO and/or NIV was 6(4–8) days before intubation or death. The mortality of patients who received ECMO is high: of 28 patients who received ECMO up to the present, 14 died, 5 weaned successfully, and 9 are still on ECMO. Lack of ventilators, fear of becoming infected during the intubation procedure, and unclear need for intubation were the main reasons for delaying invasive ventilation. Compliance with lung protective ventilation strategy is also low in some centers, with some patients receiving tidal volumes > 8 ml/kg PBW and with high driving pressures. Sedation and paralysis strategies are also not standardized. Lack of intensivists may be a potential cause. Fortunately, we found a significant benefit of prone position in most severe ARDS patients. Recommendations There should be a focus on high-risk patients, e.g., male, > 60 years old, and patients with comorbidities. Additionally, a standard protocol for SARS-CoV-2 infection recommended by World Health Organization should be widely implemented [13]. It is crucial that our staff is trained to employ standard protocols for management, which may help implement evidence-based ventilatory and general ICU care in the face of an overwhelming workload. More importantly, in the context of a multidisciplinary team, intensivists should act as leaders, ensuring that severe patients receive standardized treatment (Fig. 1). Fig. 1 Some recommendations to face the critical care crisis due to the COVID-19 epidemic In summary, the COVID-19 epidemic has placed a huge burden on the Chinese health care system. This crisis has dramatically affected the delivery of critical care due to a lack of resources, lack of prediction models and of course the lack of effective pharmacotherapies. Front line critical care clinicians desperately require these tools.

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          Most cited references10

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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 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            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.
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Summary 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.
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                Author and article information

                Contributors
                dubin98@gmail.com
                haiboq2000@163.com
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                2 March 2020
                : 1-4
                Affiliations
                [1 ]GRID grid.263826.b, ISNI 0000 0004 1761 0489, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, , Southeast University, ; Nanjing, 210009 Jiangsu China
                [2 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, , Capital Medical University, ; Beijing, 100020 China
                [3 ]GRID grid.412615.5, Department of Critical Care Medicine, , The First Affiliated Hospital of Sun Yat-sen University, ; Guangzhou, 510080 Guangdong China
                [4 ]GRID grid.12527.33, ISNI 0000 0001 0662 3178, Medical ICU, Peking Union Medical College Hospital, , Peking Union Medical College and Chinese Academy of Medical Sciences, ; Beijing, 100730 China
                [5 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Keenan Research Center at the Li Ka Shing Knowledge Institute, St. Michael’s Hospital and Departments of Medicine, Surgery, and Biomedical Engineering, , University of Toronto, ; Toronto, Canada
                Author information
                http://orcid.org/0000-0001-8589-4717
                Article
                5979
                10.1007/s00134-020-05979-7
                7080165
                32123994
                aa217751-0a3a-4276-942b-41b4c00e8603
                © Springer-Verlag GmbH Germany, part of Springer Nature 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
                : 17 February 2020
                : 19 February 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100013076, Ministry of Science and Technology of the People’s Republic of China;
                Award ID: 2020YFC0841300
                Award Recipient :
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                Emergency medicine & Trauma
                Emergency medicine & Trauma

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