Is Microthrombosis the Main Pathology in Coronavirus Disease 2019 Severity?—A Systematic Review of the Postmortem Pathologic Findings

Abstract

Objectives: This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019–associated thrombotic pathologies reported in the recent literature. Data Sources: PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020. Study Selection: Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019. Data Extraction: Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death. Data Synthesis: From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d -dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in nonsurvivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lung vasculature were the most common pathologic findings in the lungs and microthrombi in most of the assessed organ-tissue. Conclusions: Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Widespread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequent pulmonary and extrapulmonary microthrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specific hypercoagulability. Further discovery efforts in assessing the link between coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients is needed.

Mortality of Patients Infected by COVID-19 with and without Deep-Vein Thrombosis

“…One of the characteristics of COVID-19 is the involvement of multiple sites of microand macro-thrombosis in the lungs. Venous thrombotic events of the lower limbs are also seen [16][17][18]. However, these details are not part of the present study.…”

“…One hypothesis for the increase in mortality is the greater occurrence of extrapulmonary thrombosis. Micro-and macro-thrombotic events can affect the entire organism, thereby increasing the sequelae of this physiopathological process [17]. The D-dimer level practically doubles in comparison to patients without DVT, suggesting a greater volume of lysis due to the thrombotic process.…”

Double Trouble—COVID-19 and the Widespread Use of Corticosteroids: Are We Staring at an Osteonecrosis Epidemic?

“…Although it primarily affects the lungs, extra-pulmonary manifestations are frequently seen in COVID-19 [ 41 ]. This could be due to the presence of ACE2 receptors in several extra-pulmonary tissues which may cause direct viral tissue damage, endothelial damage, and dysregulation of local immune responses [ 5 , 41 , 42 ]. The ACE2 receptor is locally expressed in skeletal muscles and bone marrow-derived stem/progenitor cells (BMSPCs) [ 43 – 45 ], and their targeting by SARS-CoV-2, may lead to sarcopenia, reduced muscle strength, altered skeletal repair, and anaphasic bone loss [ 43 , 45 – 47 ].…”

Multiple Approaches at Admission Based on Lung Ultrasound and Biomarkers Improves Risk Identification in COVID-19 Patients

“…COVID-19 pathophysiology has several well-differentiated phases [ 2 ]. During the first week, a viral picture occurs that later gives way to a pro-inflammatory state [ 3 ], influenced by cytokine storm and thrombotic phenomena [ 6 ]. This situation can last for months in some cases, which is called post-COVID-19 syndrome [ 7 , 8 ].…”

“…Risk-stratification tools for COVID-19 were initially based on the analysis of baseline clinical characteristics through retrospective cohort studies during the first pandemic wave [ 1 , 9 ]. As we gathered greater knowledge about the disease and clinical experience accumulated [ 5 , 6 , 8 ], research and practice moved from clinical data to more complex analysis based on biomarkers [ 10 , 11 , 12 , 13 ], imaging [ 14 , 15 ], or functional study of the main affected organs [ 16 ].…”