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COVID-19 and Thrombosis 2023

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 19972

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Prof. Dr. Giuseppe Camporese

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Guest Editor

Department of Internal Medicine, General Medicine Unit, Thrombotic and Haemorrhagic Disorders Unit, University Hospital of Padua, Padua, Italy
Interests: vascular medicine; cardiology; coagulation and thrombotic disorders
Special Issues, Collections and Topics in MDPI journals

Dr. Pierpaolo Di Micco

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Guest Editor

UOC Medicina, Fatebenefratelli Hospital of Naples, 80131 Naples, Italy
Interests: immunology; vascular medicine; cardiology; infectious disease; neurology; coagulation and clinical laboratory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After the great success of the first edition of this Special Issue, and the persisting need for a reappraisal of the pandemic, we are very happy to open the second edition of the Special Issue on the association between COVID-19 and thrombosis.

The SARS-CoV-2 pandemic began nearly three years ago, and our work has since changed from that time.

The scientific literature has contributed to knowledge of this virus and its related infectious diseases, with an increase in the number of related submissions and articles around the world.

Many colleagues have contributed with their own clinical and laboratory experience to enable the comprehension of COVID-19, and what has since rapidly become evident since the first reports from China is the strong association existing between COVID-19 and immunopathological and thrombotic complications, as well as other serious complications, such as COVID-19-related liver or cardiac damage.

We are pleased to invite you to contribute an account of your experience relevant to knowledge of the relationship between COVID-19 and thrombotic and cardiovascular disorders, given the long period that has passed since the pandemic first arose.

The aim of this Special Issue is to report on the most recent experiences—during Q3–Q4 2021—of different authors dealing with COVID-19 and thrombosis worldwide. Scientific contributions in the form of original articles, reviews, and case reports are welcome.

We look forward to receiving your contributions about your clinical experience in the daily clinical management of COVID-19 from laboratory, clinical, instrumental diagnostics and therapeutic points of view, we are also looking for rare case reports, in particular regarding unusual site of thrombosis in inpatients with COVID-19.

Prof. Dr. Giuseppe Camporese
Dr. Pierpaolo Di Micco
Guest Editors

Manuscript Submission Information

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Keywords

COVID-19
SARS-CoV-2
immunopathological disease
venous thromboembolism
disseminated intravascular coagulation
acquired immunodeficiency
D-Dimer
microvesicles

Published Papers (11 papers)

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Editorial

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2 pages, 179 KiB

Open AccessEditorial

Editorial Comment on the Special Issue Discussing COVID-19 and Thrombosis, Second Edition

by Pierpaolo Di Micco, Alessandro Perrella and Giuseppe Camporese

Viruses 2023, 15(9), 1922; https://0-doi-org.brum.beds.ac.uk/10.3390/v15091922 - 14 Sep 2023

Viewed by 563

Abstract

The recent SARS-CoV-2 pandemic is ending after over three years, and the efforts of physicians in the daily clinical management of infection in inpatients and outpatients and vaccination campaigns allowed to medical experts to understand all possible scientific aspects of COVID-19 [...] Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

4 pages, 634 KiB

Open AccessEditorial

Editorial COVID-19 and Thrombosis 2023: New Waves of SARS-CoV-2 Infection, Triage Organization in Emergency Department and the Association of VOCs/VOI with Pulmonary Embolism

by Ciro di Gennaro, Mariano Galdiero, Giovanna Scherillo, Stefano Parlamento, Maria Rita Poggiano, Claudia Arturo, Antonio Vasta, Beniamino Giordano, Viviana Pisano, Antonio Lobasso, Giuseppe Camporese and Pierpaolo Di Micco

Viruses 2022, 14(11), 2453; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112453 - 05 Nov 2022

Cited by 7 | Viewed by 1266

Abstract

Nearly two years ago, the SARS-CoV-2 outbreak began, and our lives have changed significantly since then [...] Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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Research

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15 pages, 288 KiB

Open AccessArticle

Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ

by Anastasiya S. Babkina, Mikhail Y. Yadgarov, Alexey V. Volkov, Artem N. Kuzovlev, Andrey V. Grechko and Arkady M. Golubev

Viruses 2023, 15(8), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/v15081681 - 02 Aug 2023

Cited by 3 | Viewed by 969

Abstract

COVID-19-related thrombosis affects the venous and arterial systems. Data from 156 autopsies of COVID-19 patients were retrospectively analyzed to investigate the pattern of thrombotic complications and factors associated with pulmonary artery thrombosis and thromboembolism. Thrombotic complications were observed in a significant proportion (n = 68, 44%), with pulmonary artery thrombosis the most frequently identified thrombotic event (42, 27%). Multivariate analysis revealed that the length of hospital stay (OR 1.1, p = 0.004), neutrophil infiltration in the alveolar spaces (OR 3.6, p = 0.002), and the absence of hyaline membranes (OR 0.1, p = 0.01) were associated with thrombotic complications. Neutrophil infiltration in the alveolar spaces (OR 8, p < 0.001) and the absence of hyaline membranes (OR 0.1, p = 0.003) were also independent predictors of pulmonary artery thrombosis. The association of pulmonary artery thrombosis with an absence of hyaline membranes suggests it occurs later in the course of COVID-19 infection. As neutrophil infiltration in the alveolar spaces may indicate bacterial infection, our studies suggest the consideration of bacterial infections in these critically ill patients. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

9 pages, 251 KiB

Open AccessArticle

COVID-19 and Thromboembolic Events in the Pandemic and Pre-Pandemic Era: A Pediatric Cohort

by Chiara Rubino, Camilla Bechini, Mariangela Stinco, Donatella Lasagni, Giuseppe Indolfi and Sandra Trapani

Viruses 2023, 15(7), 1554; https://0-doi-org.brum.beds.ac.uk/10.3390/v15071554 - 15 Jul 2023

Cited by 1 | Viewed by 805

Abstract

The Coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been variably associated with thromboembolic events (TEs) in children. The aim of our study was to assess the prevalence of TEs in children hospitalized during a five-year period in a tertiary pediatric hospital, particularly in patients with COVID-19 and MIS-C. Overall, 38 patients were discharged with the diagnosis of TE: 20 in the pre-pandemic and 18 in the pandemic period. The prevalence of TEs was the same (0.08%) in the pre-pandemic and pandemic periods. The occurrence of TEs was higher in patients with COVID-19 or MIS-C (6/517, 1.16%) when compared to children without these conditions in the pandemic and in the pre-pandemic periods. The prevalence of TEs in children with MIS-C was significantly higher than the prevalence in patients with COVID-19. Five out of six of the patients with COVID-19 or MIS-C developing a TE had at least one predisposing factor to thrombosis. In conclusion, our study shows an increased prevalence of TEs in children hospitalized with COVID-19 or MIS-C, if compared to children without COVID-19 or MIS-C in the pandemic period and in the pre-pandemic period. The prevalence of TEs was significantly higher in patients with MIS-C. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

12 pages, 295 KiB

Open AccessArticle

Inflammatory Response and Activation of Coagulation after COVID-19 Infection

by Anna Glória Fonseca Teodoro, Wellington Francisco Rodrigues, Thais Soares Farnesi-de-Assunção, Anna V. Bernardes e Borges, Malu Mateus Santos Obata, José Rodrigues do Carmo Neto, Djalma A. Alves da Silva, Leonardo E. Andrade-Silva, Chamberttan S. Desidério, Juliana C. Costa-Madeira, Rafaela M. Barbosa, Andrezza C. C. Hortolani Cunha, Loren Q. Pereira, Fernanda Bernadelli de Vito, Sarah Cristina Sato Vaz Tanaka, Fernanda R. Helmo, Marcela Rezende Lemes, Laís M. Barbosa, Rafael O. Trevisan, Fabiano V. Mundim, Ana Carolina M. Oliveira-Scussel, Paulo Roberto Resende Junior, Ivan B. Monteiro, Yulsef M. Ferreira, Guilherme H. Machado, Kennio Ferreira-Paim, Hélio Moraes-Souza, Carlo José Freire de Oliveira, Virmondes Rodrigues Júnior and Marcos Vinicius da Silva Show full author list Hide full author list

Viruses 2023, 15(4), 938; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040938 - 10 Apr 2023

Cited by 5 | Viewed by 1840

Abstract

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. Methodology: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. Results: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). Conclusions: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

13 pages, 1356 KiB

Open AccessCommunication

Thrombophilia and Immune-Related Genetic Markers in Long COVID

by Rosilene da Silva, Kevin Matheus Lima de Sarges, Marcos Henrique Damasceno Cantanhede, Flávia Póvoa da Costa, Erika Ferreira dos Santos, Fabíola Brasil Barbosa Rodrigues, Maria de Nazaré do Socorro de Almeida Viana, Mauro de Meira Leite, Andréa Luciana Soares da Silva, Mioni Thieli Magalhães de Brito, Maria Karoliny da Silva Torres, Maria Alice Freitas Queiroz, Izaura Maria Vieira Cayres Vallinoto, Daniele Freitas Henriques, Carla Pinheiro dos Santos, Giselle Maria Rachid Viana, Juarez Antônio Simões Quaresma, Luiz Fábio Magno Falcão, Antonio Carlos Rosário Vallinoto and Eduardo José Melo dos Santos

Viruses 2023, 15(4), 885; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040885 - 30 Mar 2023

Cited by 3 | Viewed by 2762

Abstract

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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Review

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14 pages, 1427 KiB

Open AccessReview

Cerebrovascular Disease in COVID-19

by James E. Siegler, Savanna Dasgupta, Mohamad Abdalkader, Mary Penckofer, Shadi Yaghi and Thanh N. Nguyen

Viruses 2023, 15(7), 1598; https://0-doi-org.brum.beds.ac.uk/10.3390/v15071598 - 21 Jul 2023

Cited by 2 | Viewed by 2160

Abstract

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in healthcare. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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12 pages, 1150 KiB

Open AccessReview

Pulmonary Thrombosis despite Therapeutic Anticoagulation in COVID-19 Pneumonia: A Case Report and Literature Review

by Cristian-Mihail Niculae, Maria-Evelina Gorea, Laura-Georgiana Tirlescu, Rares-Alexandru Constantin, Ruxandra Moroti and Adriana Hristea

Viruses 2023, 15(7), 1535; https://0-doi-org.brum.beds.ac.uk/10.3390/v15071535 - 12 Jul 2023

Cited by 2 | Viewed by 1353

Abstract

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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19 pages, 2525 KiB

Open AccessReview

Molecular Mimicry of the Viral Spike in the SARS-CoV-2 Vaccine Possibly Triggers Transient Dysregulation of ACE2, Leading to Vascular and Coagulation Dysfunction Similar to SARS-CoV-2 Infection

by Christian A. Devaux and Laurence Camoin-Jau

Viruses 2023, 15(5), 1045; https://0-doi-org.brum.beds.ac.uk/10.3390/v15051045 - 25 Apr 2023

Cited by 7 | Viewed by 4014

Abstract

The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of rare cases of cardiovascular complications after mass vaccination using such formulations. Cases of high blood pressure have also been reported but were rarely documented under perfectly controlled medical supervision. The press release of these warning signals triggered a huge debate over COVID-19 vaccines’ safety. Thereby, our attention was quickly focused on issues involving the risk of myocarditis, acute coronary syndrome, hypertension and thrombosis. Rare cases of undesirable post-vaccine pathophysiological phenomena should question us, especially when they occur in young subjects. They are more likely to occur with inappropriate use of mRNA vaccine (e.g., at the time when the immune response is already very active during a low-noise infection in the process of healing), leading to angiotensin II (Ang II) induced inflammation triggering tissue damage. Such harmful effects observed after the COVID-19 vaccine evoke a possible molecular mimicry of the viral spike transiently dysregulating angiotensin converting enzyme 2 (ACE2) function. Although the benefit/risk ratio of SARS-CoV-2 spike mRNA vaccine is very favorable, it seems reasonable to suggest medical surveillance to patients with a history of cardiovascular diseases who receive the COVID-19 vaccine. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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11 pages, 654 KiB

Open AccessReview

SARS-CoV-2 Possible Etiology of Cerebral Venous Thrombosis in a Teenager: Case Report and Review of Literature

by Ioana Grigore, Ingrith Miron, Cristina Gavrilovici, Vasile Valeriu Lupu, Dorin Cristian Antal, Thomas Gabriel Schreiner, Catalin Prazaru, Ancuta Lupu, Felicia Dragan and Ecaterina Grigore

Viruses 2023, 15(2), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020405 - 31 Jan 2023

Cited by 4 | Viewed by 1350

Abstract

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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6 pages, 789 KiB

Open AccessCase Report

Ischaemic Stroke Occurring in a Patient Treated with Monoclonal Antibodies for COVID-19

by Antonio Lobasso, Ciro di Gennaro, Maria Rita Poggiano, Antonio Vasta, Raffaele Angelo Nicola Ranucci, Roberto Lobianco, Anna Giacoma Tucci, Enrico Cavaglià and Pierpaolo Di Micco

Viruses 2023, 15(6), 1235; https://0-doi-org.brum.beds.ac.uk/10.3390/v15061235 - 25 May 2023

Cited by 2 | Viewed by 1800

Abstract

Since the COVID-19 outbreak began, an association between COVID-19 and thrombotic diseases has been underlined. Although this association is more frequent with venous thromboembolism, ischaemic stroke has also been reported as a thrombotic complication in several cohorts of affected patients. Furthermore, the association between ischaemic stroke and COVID-19 has been considered a risk factor for early mortality. On the other hand, after the successful vaccination campaign, the incidence and the virulence of SARS-CoV-2 decreased, though it has been observed that COVID-19 may induce a severe infection in specific cohorts of frail subjects. For this reason, different drugs have been introduced of an antiviral action in order to improve the disease outcome of frail patients. In this field, with the arrival of a neutralizing monoclonal antibody against SARS-CoV-2, in particular, sotrovimab, a further chance to treat high-risk patients with mild-to-moderate COVID-19 arrived, achieving a concrete reduction in the risk of disease progression. We here report our clinical experience of an ischaemic stroke occurring a few minutes after the administration of sotrovimab for the treatment of moderate COVID-19 in a frail patient with chronic lymphocytic leukaemia. Other causes of ischaemic stroke were ruled out, and in order to evaluate the probability of a rare side effect, the Naranjo probability scale has also been utilized. In conclusion, among several side effects that have been described during the treatment of COVID-19 with sotrovimab, ischaemic stroke was not reported. Therefore, we here report a rare case of ischaemic stroke with early clinical manifestation after the administration of sotrovimab for the treatment of moderate COVID-19 in an immunocompromised patient for the first time. Full article

(This article belongs to the Special Issue COVID-19 and Thrombosis 2023)

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