Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Variables
2.3. Statistical Analysis
3. Results
3.1. Descriptive Statistics
3.2. Predictors of Thrombotic Complications
3.3. Regression Analysis
4. Discussion
4.1. Arterial Thrombosis In Situ in COVID-19 and Other Lung Diseases
4.2. Pathogenesis of Arterial and Venous Thrombosis
4.3. Role of Neutrophils in Thrombosis Pathogenesis
4.4. The Role of Bacterial Infection in the Pathogenesis of Thrombosis
4.5. Pathogenesis of Thrombosis According to Stage of Lung Injury in COVID-19
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Patients (n = 156) |
---|---|
Clinical and demographic characteristics | |
Sex, male | 68 (44%) 70.4 (SD 13.8) |
Age, years | |
Length of stay, days | 9 (IQR 5–13) |
Respiratory support >24 h | 100 (64%) |
Invasive mechanical ventilation >24 h | 24 (15%) |
PCR-confirmed COVID-19 (ante-mortem) | 156 (100%) |
PCR-confirmed COVID-19 (in the lungs tissue post-mortem) | 66 (42%) |
Competing/concomitant cause of death | 33 (21%) |
Complications of COVID-19 | |
Pulmonary edema | 151 (97%) |
Bilateral/unilateral lung injury | 153/3 |
Total/subtotal/lobar lung lesion | 90/58/8 |
Hemorrhagic component | 153 (98%) |
Bacterial pneumonia signs (autopsy) | 15 (9.6%) |
Pulmonary infarction | 7 (4.5%) |
Thrombotic complications | 68 (44%) |
Myocardial infarction | 6 (3.8%) |
Stroke | 3 (1.9%) |
Spleen infarction | 2 (1.3%) |
Renal infarction | 4 (2.6%) |
Immediate cause of death | |
Respiratory failure | 125 (80%) |
Cardiorespiratory failure | 15 (9.6%) |
Massive pulmonary embolism | 11 (7.1%) |
Cerebral edema with herniation | 4 (2.6%) |
Acute heart failure | 1 (0.6%) |
Comorbidity | |
Hypertension | 144 (92%) |
Atherosclerosis | 146 (94%) |
Coronary heart disease | 26 (17%) |
Obesity | 54 (35%) |
Diabetes mellitus | 45 (29%) |
Chronic respiratory disease | 113 (72%) |
Chronic kidney and urinary tract disease | 29 (19%) |
Chronic gastrointestinal diseases | 113 (72%) |
Chronic liver disease | 91 (58%) |
Neurodegenerative diseases | 23 (15%) |
Cerebrovascular disease | 20 (13%) |
Malignant neoplastic disease | 17 (11%) |
Thrombotic Complications | Patients (n = 156) |
---|---|
Pulmonary artery embolism (source of thromboembolism identified) | 16 (10%) |
Deep vein thrombosis of the lower extremities | 18 (12%) |
Pulmonary vein thrombosis | 9 (5.8%) |
Pulmonary artery thrombosis | 42 (27%) |
Aortic thrombosis | 3 (1.9%) |
Right atrium thrombi | 4 (2.6%) |
Coronary artery thrombosis | 3 (1.9%) |
Renal artery thrombosis | 1 (0.6%) |
Cerebral artery thrombosis | 3 (1.9%) |
Lung Histology | Patients (n = 156) |
---|---|
Fibrosis | 119 (76%) |
Interstitial/alveolar edema | 42 (27%) |
Hyaline membranes | 134 (86%) |
Neutrophil infiltration in the alveolar spaces | 54 (35%) |
Neutrophil infiltration in the bronchi | 31 (20%) |
Lung lymphocytic infiltration | 142 (91%) |
Lymphocytic infiltration of the bronchi | 29 (19%) |
Vascular congestion | 129 (83%) |
Alveolar hemorrhage | 65 (42%) |
Squamous metaplasia | 22 (14%) |
Pneumocytes with nuclear atypia | 25 (16%) |
Thrombosis of arteries/arterioles | 32 (21%) |
Thrombosis of veins/venules | 5 (3.2%) |
Desquamation of pneumocytes | 125 (80%) |
Desquamation of bronchial epithelial cells | 118 (76%) |
Acute phase signs | 5 (3.2%) |
Organizing phase signs | 32 (21%) |
Fibrotic phase signs | 119 (76%) |
Phase | Acute, n = 5 | Fibrotic, n = 119 | Organizing, n = 32 | p Value |
---|---|---|---|---|
Pulmonary artery thrombosis | 0 (0%) | 32 (27%) | 10 (31%) | 0.4 * |
Pulmonary vein thrombosis | 1 (20%) | 7 (5.9%) | 1 (3.1%) | 0.3 * |
Pulmonary embolism | 1 (20%) | 14 (12%) | 1 (3.1%) | 0.2 * |
Parameter | Patients without Thrombotic Complications (n = 88) | Patients with Thrombotic Complications (n = 68) | p Value |
---|---|---|---|
Clinical and demographic characteristics | |||
Sex, male | 37 (42%) 70 (SD 14) | 31 (46%) | 0.7 3 |
Age, years | 70 (SD 14) | 0.9 1 | |
Length of stay, d | 8 (IQR 5–11) | 11 (IQR 7–16) | 0.002 2 |
Respiratory support >24 h | 56 (64%) | 44 (65%) | 0.9 3 |
Invasive mechanical ventilation >24 h | 14 (16%) | 10 (15%) | 0.8 3 |
PCR-confirmed COVID-19 (ante-mortem) | 88 (100%) | 68 (100%) | 0.9 4 |
PCR-confirmed COVID-19 (in the lungs tissue post-mortem) | 38 (43%) | 28 (41%) | 0.9 3 |
Competing/concomitant cause of death | 11 (13%) | 12 (18%) | 0.4 3 |
Complications of COVID-19 | |||
Pulmonary edema | 86 (98%) | 65 (96%) | 0.7 4 |
Bilateral/unilateral lung injury | 86/2 | 67/1 | 0.9 4 |
Total/subtotal/lobar lung lesion | 44/38/6 | 46/20/2 | 0.08 3 |
Hemorrhagic component | 86 (98%) | 67 (99%) | 0.9 4 |
Bacterial pneumonia signs (autopsy) | 3 (3.4%) | 12 (18%) | 0.005 4 |
Pulmonary infarction | 0 (0%) | 7 (10%) | 0.002 4 |
Myocardial infarction | 2 (2.3%) | 4 (5.9%) | 0.4 4 |
Stroke | 1 (1.1%) | 2 (2.9%) | 0.6 4 |
Spleen infarction | 0 (0%) | 2 (2.9%) | 0.2 4 |
Renal infarction | 0 (0%) | 4 (5.9%) | 0.034 4 |
Immediate cause of death | |||
Respiratory failure | 78 (89%) | 47 (69%) | |
Cardiorespiratory failure | 7 (8.0%) | 8 (12%) | |
Massive pulmonary embolism | 0 (0%) | 11 (16%) | <0.001 5 |
Cerebral edema with herniation | 2 (2.3%) | 2 (2.9%) | |
Acute heart failure | 1 (1.1%) | 0 (0%) | |
Comorbidity | |||
Hypertension | 81 (92%) | 63 (93%) | 0.9 4 |
Atherosclerosis | 82 (93%) | 64 (94%) | 0.9 4 |
Coronary heart disease | 14 (16%) | 12 (18%) | 0.8 3 |
Obesity | 34 (39%) | 20 (29%) | 0.2 3 |
Diabetes mellitus | 28 (32%) | 17 (25%) | 0.4 3 |
Chronic respiratory disease | 63 (72%) | 50 (74%) | 0.8 3 |
Chronic kidney and urinary tract disease | 11 (13%) | 18 (27%) | 0.026 3 |
Chronic gastrointestinal diseases | 61 (70%) | 52 (77%) | 0.3 3 |
Chronic liver disease | 56 (64%) | 35 (52%) | 0.13 3 |
Neurodegenerative diseases | 5 (5.7%) | 18 (27%) | <0.001 4 |
Cerebrovascular disease | 8 (9.1%) | 12 (18%) | 0.15 4 |
Malignant neoplastic disease | 10 (11%) | 7 (10%) | 0.9 4 |
Lung morphologic changes | |||
Fibrosis | 64 (73%) | 55 (81%) | 0.2 3 |
Interstitial/alveolar edema | 28 (32%) | 14 (21%) | 0.1 3 |
Hyaline membranes | 86 (98%) | 48 (71%) | <0.001 3 |
Neutrophil infiltration in the alveolar spaces | 16 (18%) | 38 (56%) | <0.001 3 |
Neutrophil infiltration of the bronchi | 13 (15%) | 18 (27%) | 0.069 3 |
Lung lymphocytic infiltration | 78 (89%) | 64 (94%) | 0.2 3 |
Lymphocytic infiltration in the bronchi | 20 (23%) | 9 (13%) | 0.13 3 |
Vascular congestion | 72 (82%) | 57 (84%) | 0.7 3 |
Alveolar hemorrhage | 32 (36%) | 33 (49%) | 0.13 3 |
Squamous metaplasia | 9 (10%) | 13 (19%) | 0.16 4 |
Pneumocytes with nuclear atypia | 11 (13%) | 14 (21%) | 0.2 3 |
Thrombosis of arteries/arterioles | 0 (0%) | 32 (47%) | <0.001 4 |
Thrombosis of veins/venules | 0 (0%) | 5 (7.4%) | 0.014 4 |
Desquamation of pneumocytes | 76 (86%) | 49 (72%) | 0.026 3 |
Desquamation of bronchial epithelial cells | 71 (81%) | 47 (69%) | 0.095 3 |
Acute phase signs | 3 (3.4%) | 2 (2.9%) | 0.5 3 |
Organizing phase signs | 21 (23.9%) | 11 (16%) | |
Fibrotic phase signs | 64 (72.7%) | 55 (81%) |
Parameter | Univariable Analysis | Multivariable Analysis | ||||
---|---|---|---|---|---|---|
OR | 95% CI | p Value | OR | 95% CI | p Value | |
Length of stay, days | 1.11 | 1.04–1.18 | 0.001 | 1.11 | 1.03–1.19 | 0.004 |
Bacterial pneumonia signs (autopsy) | 6.07 | 1.64–22.48 | 0.007 | NS | 0.9 | |
Chronic kidney and urinary tract disease | 2.52 | 1.1–5.78 | 0.029 | NS | 0.3 | |
Neurodegenerative diseases | 5.98 | 2.09–17.1 | <0.001 | NS | 0.2 | |
Hyaline membranes | 0.06 | 0.01–0.25 | <0.001 | 0.12 | 0.03–0.60 | 0.01 |
Neutrophil infiltration in the alveolar spaces | 5.7 | 2.77–11.74 | <0.001 | 3.61 | 1.60–8.18 | 0.002 |
Desquamation of pneumocytes | 0.41 | 0.18–0.91 | 0.029 | NS | 0.8 |
Parameter | Univariable Analysis | Multivariable Analysis | ||||
---|---|---|---|---|---|---|
OR | 95% CI | p Value | OR | 95% CI | p Value | |
Length of stay, days | 1.09 | 1.02–1.15 | 0.008 | NS | 0.06 | |
Bacterial pneumonia signs (autopsy) | 9.76 | 2.91–32.78 | <0.001 | NS | 0.7 | |
Chronic kidney and urinary tract disease | 2.75 | 1.18–6.37 | 0.019 | NS | 0.2 | |
Neurodegenerative diseases | 5.83 | 2.29–14.87 | <0.001 | NS | 0.5 | |
Hyaline membranes | 0.05 | 0.02–0.16 | <0.001 | 0.14 | 0.04–0.52 | 0.003 |
Neutrophil infiltration in the alveolar spaces | 13.38 | 5.73–31.27 | <0.001 | 7.95 | 3.12–20.25 | <0.001 |
Desquamation of pneumocytes | 0.21 | 0.09–0.47 | <0.001 | NS | 0.4 |
Parameter | Univariable Analysis | ||
---|---|---|---|
OR | 95% CI | p Value | |
Length of stay, days | 1.06 | 0.97–1.15 | 0.07 |
Bacterial pneumonia signs (autopsy) | 1.40 | 0.29–6.83 | 0.7 |
Chronic kidney and urinary tract disease | 0.73 | 0.15–3.47 | 0.2 |
Neurodegenerative diseases | NA | 0.3 | |
Hyaline membranes | NA | 0.9 | |
Neutrophil infiltration in the alveolar spaces | 0.51 | 0.14–1.9 | 0.8 |
Desquamation of pneumocytes | 1.57 | 0.33–7.4 | 0.6 |
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Babkina, A.S.; Yadgarov, M.Y.; Volkov, A.V.; Kuzovlev, A.N.; Grechko, A.V.; Golubev, A.M. Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ. Viruses 2023, 15, 1681. https://doi.org/10.3390/v15081681
Babkina AS, Yadgarov MY, Volkov AV, Kuzovlev AN, Grechko AV, Golubev AM. Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ. Viruses. 2023; 15(8):1681. https://doi.org/10.3390/v15081681
Chicago/Turabian StyleBabkina, Anastasiya S., Mikhail Y. Yadgarov, Alexey V. Volkov, Artem N. Kuzovlev, Andrey V. Grechko, and Arkady M. Golubev. 2023. "Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ" Viruses 15, no. 8: 1681. https://doi.org/10.3390/v15081681
APA StyleBabkina, A. S., Yadgarov, M. Y., Volkov, A. V., Kuzovlev, A. N., Grechko, A. V., & Golubev, A. M. (2023). Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ. Viruses, 15(8), 1681. https://doi.org/10.3390/v15081681