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      Early recognition of low-risk SARS-CoV-2 pneumonia: A model validated with initial data and IDSA/ATS minor criteria

      research-article
      Author(s): , MD, PhD 1 , 2 , 3 , 4 , ∗∗ , ∗ , , MD, PhD 1 , 2 , ∗∗∗ , ∗ , , MD 1 , 2 , 3 , , MD, PhD 5 , , MD 5 , 6 , , MD 5 , 6 , , MD, PhD 7 , , MD, PhD 7 , , PhD 4 , 8 , 9 , 10 , , MD, PhD 11 , , MD, PhD 11 , , MD, PhD 4 , 8 , 9 , 10
      Publication date (Electronic):
      Journal: Chest
      Publisher: Published by Elsevier Inc under license from the American College of Chest Physicians.
      Keywords: SARS-CoV-2, COVID-19, risk profiling, pneumonia, IDSA/ATS, AST, Aspartate Transaminase, ATS, American Thoracic Society, AUROC, Area Under the Receiver Operating Characteristic Curve, CAP, Community-acquired Pneumonia, CI, Confidence Interval, COPD, Chronic Obstructive Pulmonary Disease, COVID-19, Coronavirus Disease 2019, CRP, C-reactive Protein, FiO2, Fraction of Inspired Oxygen, ER, Emergency Room, DD, D-dimer, ICU, Intensive Care Unit, IDSA, Infectious Diseases Society of America, LDH, Lactate Dehydrogenase, NPV, Negative Predictive Value, OR, Odds Ratio, PPV, Positive Predictive Value, RT-PCR, Reverse Transcription Polymerase Chain Reaction, SARS-Cov-2, Severe Acute Respiratory Syndrome Coronavirus 2, SpO2, Peripheral Blood Oxygen Saturation, TRIPOD, Transparent Reporting of Multivariable Prediction Model for Individual Prognosis Or Diagnosis , WBC, White Blood Cells., WHO, World Health Organization

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          Abstract

          Background

          A shortage of beds in the intensive care unit (ICU) and conventional ward during the COVID-19 pandemic led to a collapse of healthcare resources.

          Research Question.

          Can admission data and minor criteria by the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) help identify patients with low-risk SARS-CoV-2 pneumonia?

          Study Design and Methods

          This multicenter cohort study included 1274 patients in a derivation cohort and 830 (first wave) and 754 (second wave) in two validation cohorts. A multinomial regression analysis was performed on the derivation cohort to compare the following patients: those admitted to the ward (assessed as low-risk); those admitted to the ICU directly; those transferred to the ICU after general ward admission; and those who died. A regression analysis identified independent factors for low-risk pneumonia. The model was subsequently validated.

          Results

          In the derivation cohort, similarities existed among those either directly admitted or transferred to the ICU and those who died. These patients could, therefore, be merged into one group. We identified five independently-associated factors as being predictors of low risk (not dying and/or requiring ICU admission) (odds ratios, with 95% confidence intervals): SpO 2/FiO 2 > 450 (0.233; CI 0.149-0.364); < 3 IDSA/ATS minor criteria (0.231; 0.146-0.365); lymphocyte count > 723 cells/mL (0.539; 0.360-0.806); urea < 40 mg/dL (0.651; 0.426-0.996); and C-reactive protein < 60 mg/L (0.454; 0.285-0.724). The areas under the curve were 0.802 (0.769-0.835) in the derivation cohort, and 0.779 (0.742-0.816) and 0.801 (0.757-0.845) for the validation cohorts (first and second waves, respectively).

          Interpretation.

          Initial biochemical findings and the application of <3 IDSA/ATS minor criteria make early identification of low-risk SARS-CoV-2 pneumonia (approximately 80% of hospitalized patients) feasible. This scenario could facilitate and streamline healthcare resource allocation for patients with COVID-19.

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

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          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 course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

            Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)
            Summary 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.
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              COVID-19: consider cytokine storm syndromes and immunosuppression

              Puja Mehta, Daniel McAuley, Michael Brown … (2020)
              As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Chest
                Journal ID (iso-abbrev): Chest
                Title: Chest
                Publisher: Published by Elsevier Inc under license from the American College of Chest Physicians.
                ISSN (Print): 0012-3692
                ISSN (Electronic): 1931-3543
                Publication date PMC-release: 21 May 2022
                Publication date (Electronic): 21 May 2022
                Affiliations
                [1 ]Pneumology Department. La Fe University and Polytechnic Hospital. Valencia, Spain
                [2 ]Respiratory Infections. Health Research Institute La Fe (IISLAFE). Valencia, Spain
                [3 ]University of Valencia. Valencia, Spain
                [4 ]Center for Biomedical Research Network in Respiratory Diseases (CIBERES). Madrid, Spain
                [5 ]Pneumology Department. Cruces University Hospital. Barakaldo, Spain
                [6 ]Department of Immunology, Microbiology and Parasitology. Facultad de Medicina y Enfermería, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU. Leioa, Bizkaia, Spain
                [7 ]Pneumology Department. Galdakao-Usansolo Hospital. Galdacano, Spain
                [8 ]University of Barcelona. Barcelona, Spain
                [9 ]Pneumology Department. Hospital Clinic of Barcelona. Barcelona, Spain
                [10 ]August Pi i Sunyer Biomedical Research Institute. Barcelona, Spain
                [11 ]Pneumology Department. Lucus Augusti University Hospital. Lugo, Spain
                Author notes
                [∗∗ ] Corresponding author: Rosario Menéndez, Servicio de Neumología. Hospital Universitario y Politécnico La Fe, Avda. Fernando Abril Martorell 106, 46026 Valencia. Spain,
                [∗∗∗ ] Corresponding author: Raúl Méndez, Servicio de Neumología. Hospital Universitario y Politécnico La Fe, Avda. Fernando Abril Martorell 106, 46026 Valencia. Spain,
                [∗]

                Equal contribution

                Article
                Publisher Item ID: S0012-3692(22)01007-8
                DOI: 10.1016/j.chest.2022.05.013
                PMC ID: 9124046
                PubMed ID: 35609674
                SO-VID: 3f57fec8-87b0-4c3b-b8f9-3f5a4088e8ed
                Copyright © © 2022 Published by Elsevier Inc under license from the American College of Chest Physicians.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 16 November 2021
                Date revision received : 20 April 2022
                Date accepted : 13 May 2022
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Respiratory medicine
                Keywords: sars-cov-2,covid-19,risk profiling,pneumonia,idsa/ats,ast, aspartate transaminase,ats, american thoracic society,auroc, area under the receiver operating characteristic curve,cap, community-acquired pneumonia,ci, confidence interval,copd, chronic obstructive pulmonary disease,covid-19, coronavirus disease 2019,crp, c-reactive protein,fio2, fraction of inspired oxygen,er, emergency room,dd, d-dimer,icu, intensive care unit,idsa, infectious diseases society of america,ldh, lactate dehydrogenase,npv, negative predictive value,or, odds ratio,ppv, positive predictive value,rt-pcr, reverse transcription polymerase chain reaction,sars-cov-2, severe acute respiratory syndrome coronavirus 2,spo2, peripheral blood oxygen saturation,tripod, transparent reporting of multivariable prediction model for individual prognosis or diagnosis,wbc, white blood cells.,who, world health organization
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: sars-cov-2, covid-19, risk profiling, pneumonia, idsa/ats, ast, aspartate transaminase, ats, american thoracic society, auroc, area under the receiver operating characteristic curve, cap, community-acquired pneumonia, ci, confidence interval, copd, chronic obstructive pulmonary disease, covid-19, coronavirus disease 2019, crp, c-reactive protein, fio2, fraction of inspired oxygen, er, emergency room, dd, d-dimer, icu, intensive care unit, idsa, infectious diseases society of america, ldh, lactate dehydrogenase, npv, negative predictive value, or, odds ratio, ppv, positive predictive value, rt-pcr, reverse transcription polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2, spo2, peripheral blood oxygen saturation, tripod, transparent reporting of multivariable prediction model for individual prognosis or diagnosis, wbc, white blood cells., who, world health organization

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