Download PDF
Thromb Haemost 2022; 122(02): 257-266
DOI: 10.1055/a-1692-9939
Stroke, Systemic or Venous Thromboembolism

Comparison of Thrombotic Events and Mortality in Patients with Community-Acquired Pneumonia and COVID-19: A Multicenter Observational Study

Roberto Cangemi
1   Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
,
Camilla Calvieri
2   Department of Clinical Internal, I Clinica Medica, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Marco Falcone
3   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Francesco Cipollone
4   Department of Medicine and Aging, “G. D'Annunzio” University of Chieti-Pescara, Chieti, Italy
,
Giancarlo Ceccarelli
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Pasquale Pignatelli
2   Department of Clinical Internal, I Clinica Medica, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
6   Mediterranea Cardiocentro, Naples, Italy
,
Damiano D'Ardes
4   Department of Medicine and Aging, “G. D'Annunzio” University of Chieti-Pescara, Chieti, Italy
,
Matteo Pirro
7   Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, Italy
,
Francesco Alessandri
8   Department of General Surgery Paride Stefanini, Sapienza University of Rome, Rome, Italy
,
Miriam Lichtner
9   Infectious Diseases Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
,
Gabriella D'Ettorre
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Alessandra Oliva
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Raissa Aronica
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Monica Rocco
10   Department of Clinical and Surgical Translational Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
,
Mario Venditti
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Giulio Francesco Romiti 
1   Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
,
Giusy Tiseo
3   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Gloria Taliani
1   Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
,
Francesco Menichetti
3   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Francesco Pugliese
8   Department of General Surgery Paride Stefanini, Sapienza University of Rome, Rome, Italy
,
Claudio Maria Mastroianni
5   Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
,
Francesco Violi
2   Department of Clinical Internal, I Clinica Medica, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
6   Mediterranea Cardiocentro, Naples, Italy
› Author Affiliations Funding This study was funded by Sapienza University of Rome (grant No. RM118164366B89BD to F.V.).
› Further Information
   Permissions and Reprints

Abstract

Background It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival.

Methods In this multicenter observational cohort study, 1,138 patients, hospitalized for CAP (n = 559) or COVID-19 (n = 579) from seven clinical centers in Italy, were included in the study. Consecutive adult patients (age ≥ 18 years) with confirmed COVID-19-related pneumonia, with or without mechanical ventilation, hospitalized from March 1, 2020 to April 30, 2020, were enrolled. COVID-19 was diagnosed based on the World Health Organization interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events.

Results During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p = 0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses.

During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p < 0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6 vs. 13.4% in thrombotic-event-free patients; p < 0.001). In CAP, 13.8% of patients experiencing thrombotic events died versus 1.8% of thrombotic event-free ones (p < 0.001). A multivariable Cox-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (hazard ratio: 2.1; 95% confidence interval: 1.4–3.3; p < 0.001).

Conclusion Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.

Keywords

community-acquired pneumonia - COVID-19 - thrombosis


Publication History

Received: 25 May 2021

Accepted: 08 November 2021

Accepted Manuscript online:
10 November 2021

Article published online:
29 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Bikdeli B, Madhavan MV, Jimenez D. et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
    CrossrefPubMedGoogle Scholar
  • 2 Violi F, Pastori D, Cangemi R, Pignatelli P, Loffredo L. Hypercoagulation and antithrombotic treatment in coronavirus 2019: a new challenge. Thromb Haemost 2020; 120 (06) 949-956
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Katneni UK, Alexaki A, Hunt RC. et al. Coagulopathy and thrombosis as a result of severe COVID-19 infection: a microvascular focus. Thromb Haemost 2020; 120 (12) 1668-1679
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Al-Samkari H, Karp Leaf RS, Dzik WH. et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 2020; 136 (04) 489-500
    CrossrefPubMedGoogle Scholar
  • 5 Jain S, Self WH, Wunderink RG. et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015; 373 (05) 415-427
    CrossrefPubMedGoogle Scholar
  • 6 Pletz MW, Blasi F, Chalmers JD. et al. International perspective on the new 2019 American Thoracic Society/Infectious Diseases Society of America Community-Acquired Pneumonia Guideline: A Critical Appraisal by a Global Expert Panel. Chest 2020; 158 (05) 1912-1918
    CrossrefPubMedGoogle Scholar
  • 7 Cangemi R, Calvieri C, Falcone M. et al; SIXTUS Study Group. Relation of cardiac complications in the early phase of community-acquired pneumonia to long-term mortality and cardiovascular events. Am J Cardiol 2015; 116 (04) 647-651
    CrossrefPubMedGoogle Scholar
  • 8 Violi F, Cangemi R, Falcone M. et al; SIXTUS (Thrombosis-Related Extrapulmonary Outcomes in Pneumonia) Study Group. Cardiovascular complications and short-term mortality risk in community-acquired pneumonia. Clin Infect Dis 2017; 64 (11) 1486-1493
    CrossrefPubMedGoogle Scholar
  • 9 Mei F, Fan J, Yuan J. et al. Comparison of venous thromboembolism risks between COVID-19 pneumonia and community-acquired pneumonia patients. Arterioscler Thromb Vasc Biol 2020; 40 (09) 2332-2337
    CrossrefPubMedGoogle Scholar
  • 10 Cangemi R, Casciaro M, Rossi E. et al; SIXTUS Study Group, SIXTUS Study Group. Platelet activation is associated with myocardial infarction in patients with pneumonia. J Am Coll Cardiol 2014; 64 (18) 1917-1925
    CrossrefPubMedGoogle Scholar
  • 11 Falcone M, Venditti M, Shindo Y, Kollef MH. Healthcare-associated pneumonia: diagnostic criteria and distinction from community-acquired pneumonia. Int J Infect Dis 2011; 15 (08) e545-e550
    CrossrefPubMedGoogle Scholar
  • 12 Ye Z, Zhang Y, Wang Y, Huang Z, Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol 2020; 30 (08) 4381-4389
    CrossrefPubMedGoogle Scholar
  • 13 Metlay JP, Waterer GW, Long AC. et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200 (07) e45-e67
    CrossrefPubMedGoogle Scholar
  • 14 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
    CrossrefPubMedGoogle Scholar
  • 15 Thygesen K, Alpert JS, Jaffe AS. et al; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018). Circulation 2018; 138 (20) e618-e651
    CrossrefPubMedGoogle Scholar
  • 16 Kernan WN, Ovbiagele B, Black HR. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45 (07) 2160-2236
    CrossrefPubMedGoogle Scholar
  • 17 Bonaca MP, Gutierrez JA, Creager MA. et al. Acute limb ischemia and outcomes with vorapaxar in patients with peripheral artery disease: results from the trial to assess the effects of vorapaxar in preventing heart attack and stroke in patients with atherosclerosis-thrombolysis in myocardial infarction 50 (TRA2°P-TIMI 50). Circulation 2016; 133 (10) 997-1005
    CrossrefPubMedGoogle Scholar
  • 18 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (:2, Suppl): e419S-e496S
    CrossrefPubMedGoogle Scholar
  • 19 Loffredo L, Arienti V, Vidili G. et al; AURELIO Study Group. Low rate of intrahospital deep venous thrombosis in acutely ill medical patients: results from the AURELIO study. Mayo Clin Proc 2019; 94 (01) 37-43
    CrossrefPubMedGoogle Scholar
  • 20 Hulshof AM, Brüggemann RAG, Mulder MMG. et al. Serial EXTEM, FIBTEM, and tPA rotational thromboelastometry observations in the Maastricht intensive care COVID cohort-persistence of hypercoagulability and hypofibrinolysis despite anticoagulation. Front Cardiovasc Med 2021; 8: 654174
    CrossrefPubMedGoogle Scholar
  • 21 Mulder MMG, Brandts L, Brüggemann RAG. et al. Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort. Thromb J 2021; 19 (01) 35
    CrossrefPubMedGoogle Scholar
  • 22 Santos-Gallego CG, Badimon JJ. The sum of two evils: pneumonia and myocardial infarction: is platelet activation the missing link?. J Am Coll Cardiol 2014; 64 (18) 1926-1928
    CrossrefPubMedGoogle Scholar
  • 23 Falcone M, Russo A, Cangemi R. et al. Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin. J Am Heart Assoc 2015; 4 (01) e001595
    CrossrefPubMedGoogle Scholar
  • 24 Ucan ES, Ozgen Alpaydin A, Ozuygur SS. et al; DEU COVID Study Group. Pneumonia severity indices predict prognosis in coronavirus disease-2019. Respir Med Res 2021; 79: 100826
    PubMedGoogle Scholar
  • 25 Lazar Neto F, Marino LO, Torres A. et al; COVID Registry Team, Medical Students, Residents, Attending physicians. Community-acquired pneumonia severity assessment tools in patients hospitalized with COVID-19: a validation and clinical applicability study. Clin Microbiol Infect 2021; 27 (07) 1037.e1-1037.e8
    CrossrefPubMedGoogle Scholar
  • 26 Violi F, Cangemi R, Romiti GF. et al. Is albumin predictor of mortality in COVID-19?. Antioxid Redox Signal 2021; 35 (02) 139-142
    CrossrefPubMedGoogle Scholar
  • 27 Ronit A, Kirkegaard-Klitbo DM, Dohlmann TL. et al. Plasma albumin and incident cardiovascular disease: results from the CGPS and an updated meta-analysis. Arterioscler Thromb Vasc Biol 2020; 40 (02) 473-482
    CrossrefPubMedGoogle Scholar
  • 28 Tian R, Wu W, Wang C. et al. Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study. Sci Rep 2020; 10 (01) 17524
    CrossrefPubMedGoogle Scholar
  • 29 Taus F, Salvagno G, Canè S. et al. Platelets promote thromboinflammation in SARS-CoV-2 pneumonia. Arterioscler Thromb Vasc Biol 2020; 40 (12) 2975-2989
    CrossrefPubMedGoogle Scholar
  • 30 Cangemi R, Falcone M, Taliani G. et al; SIXTUS Study Group. Corticosteroid use and incident myocardial infarction in adults hospitalized for community-acquired pneumonia. Ann Am Thorac Soc 2019; 16 (01) 91-98
    CrossrefPubMedGoogle Scholar
  • 31 Cangemi R, Carnevale R, Nocella C. et al; SIXTUS Study Group. Glucocorticoids impair platelet thromboxane biosynthesis in community-acquired pneumonia. Pharmacol Res 2018; 131: 66-74
    CrossrefPubMedGoogle Scholar
  • 32 Basili S, Carnevale R, Nocella C. et al; PRO-LIVER Collaborators. Serum albumin is inversely associated with portal vein thrombosis in cirrhosis. Hepatol Commun 2019; 3 (04) 504-512
    CrossrefPubMedGoogle Scholar