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      Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience

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          Abstract

          Background and aims

          Several studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes.

          Methods

          This is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi0 2≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5μg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed.

          Results

          Among 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas.

          Conclusions

          Despite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas.

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

            Nanshan Chen, Min Zhou, Xuan Dong … (2022)
            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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              Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

              Ning Tang, Dengju Li, Xiong Wang … (2020)
              Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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                Author and article information

                Contributors
                Marco Loffi:
                ORCID: https://orcid.org/0000-0002-1682-1386
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Valentina Regazzoni: Role: ConceptualizationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Marco Toselli: Role: ConceptualizationRole: Data curation
                Alberto Cereda: Role: Visualization
                Anna Palmisano: Role: Data curationRole: Methodology
                Davide Vignale:
                ORCID: https://orcid.org/0000-0002-2692-7432
                Role: Data curation
                Francesco Moroni: Role: Data curation
                Gianluca Pontone:
                ORCID: https://orcid.org/0000-0002-1339-6679
                Role: SupervisionRole: ValidationRole: Visualization
                Daniele Andreini: Role: SupervisionRole: ValidationRole: Visualization
                Elisabetta Maria Mancini: Role: Data curationRole: Visualization
                Alberto Monello:
                ORCID: https://orcid.org/0000-0002-6123-7322
                Role: Data curationRole: Validation
                Gianmarco Iannopollo: Role: Data curationRole: ValidationRole: Visualization
                Gianni Casella: Role: Data curationRole: Validation
                Francesco Monetti: Role: Data curationRole: Validation
                Lorenzo Monti: Role: Data curationRole: SupervisionRole: Validation
                Giuseppe Ferrillo: Role: Data curationRole: Validation
                Gaetano Liccardo:
                ORCID: https://orcid.org/0000-0002-3883-1622
                Role: Data curationRole: Validation
                Elisabetta Tonet: Role: Data curationRole: Visualization
                Ottavio Zucchetti: Role: Data curation
                Alberto Cossu:
                ORCID: https://orcid.org/0000-0002-3462-1695
                Role: Data curation
                Marco Dugo:
                ORCID: https://orcid.org/0000-0002-7822-4587
                Role: Data curation
                Gianluigi Patelli: Role: ConceptualizationRole: Data curationRole: Validation
                Pietro Sergio: Role: Data curationRole: SoftwareRole: ValidationRole: Visualization
                Antonio Esposito: Role: ConceptualizationRole: InvestigationRole: SupervisionRole: ValidationRole: Visualization
                Antonio Colombo: Role: SupervisionRole: Validation
                Francesco Giannini: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Supervision
                Raffaele Piccolo: Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Gian Battista Danzi: Role: Project administrationRole: SupervisionRole: Writing – review & editing
                Pablo Garcia de Frutos: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 22 January 2021
                Publication date Collection: 2021
                Publication date PMC-release: 22 January 2021
                Volume: 16
                Issue: 1
                Electronic Location Identifier: e0245565
                Affiliations
                [1 ] Department of Cardiology, Ospedale di Cremona, Cremona, Italy
                [2 ] Department of Cardiology, GVM Care & Research Maria Cecilia Hospital, Cotignola (RA), Italy
                [3 ] Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milano, Italy
                [4 ] School of Medicine, Vita-Salute San Raffaele University, Milano, Italy
                [5 ] Department of Cardiology, IRCCS Ospedale San Raffaele, Milano, Italy
                [6 ] Department of Cardiology, IRCCS Centro Cardiologico Monzino, Milano, Italy
                [7 ] Department of Cardiology, Guglielmo da Saliceto Hospital, Piacenza, Italy
                [8 ] Department of Cardiology, Ospedale Maggiore, Bologna, Italy
                [9 ] Department of Cardiology, IRCCS Humanitas Clinical and Research Hospital, Rozzano (MI), Italy
                [10 ] Department of Cardiology, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
                [11 ] Department of Cardiology, Ospedale Bolognini, Seriate (BG), Italy
                [12 ] Department of Radiology, Ospedale di Cremona, Cremona, Italy
                [13 ] Department of Cardiology, University of Naples Federico II, Naples, Italy
                Institut d'Investigacions Biomediques de Barcelona, SPAIN
                Author notes

                Competing Interests: The authors also have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-1682-1386
                https://orcid.org/0000-0002-2692-7432
                https://orcid.org/0000-0002-1339-6679
                https://orcid.org/0000-0002-6123-7322
                https://orcid.org/0000-0002-3883-1622
                https://orcid.org/0000-0002-3462-1695
                https://orcid.org/0000-0002-7822-4587
                Article
                Publisher ID: PONE-D-20-33946
                DOI: 10.1371/journal.pone.0245565
                PMC ID: 7822531
                PubMed ID: 33481902
                SO-VID: 684106f8-cccd-4cde-a902-5a87bd3c025d
                Copyright © © 2021 Loffi et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 28 October 2020
                Date accepted : 4 January 2021
                Page count
                Figures: 2, Tables: 5, Pages: 12
                Funding
                I further certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript and the authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Pneumonia
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Biology and life sciences
                Subject: Microbiology
                Subject: Medical microbiology
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Medicine and health sciences
                Subject: Pathology and laboratory medicine
                Subject: Pathogens
                Subject: Microbial pathogens
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral pathogens
                Subject: Coronaviruses
                Subject: SARS coronavirus
                Subject: SARS CoV 2
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Pulmonary Embolism
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Thromboembolism
                Subject: Venous Thromboembolism
                Subject: Pulmonary Embolism
                Subject: Medicine and Health Sciences
                Subject: Pharmaceutics
                Subject: Drug Therapy
                Subject: Cardiovascular Therapy
                Subject: Anticoagulant Therapy
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Viral Diseases
                Subject: Covid 19
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Medical Risk Factors
                Subject: Physical Sciences
                Subject: Chemistry
                Subject: Chemical Elements
                Subject: Oxygen
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Neuroimaging
                Subject: Computed Axial Tomography
                Subject: Biology and Life Sciences
                Subject: Neuroscience
                Subject: Neuroimaging
                Subject: Computed Axial Tomography
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Computed Axial Tomography
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Computed Axial Tomography
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Tomography
                Subject: Computed Axial Tomography
                Custom metadata
                Data Availability We have not shared our minimal data set because our database contains multicenter data and we currently do not have permission to share data from all participating centers. Furthermore, the request of the permission to share the data from all the centers could take time. However, we will work on that during peer review for our revisions in order to obtain the permission to share the data from every center involved in the study and we will provide an update should our manuscript be accepted.
                Outbreaks COVID-19

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