COVID-19 Cardio/ Cardiovascular / Pulmonary

Updated September 28, 2023

8 APR 2020: Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19 (NEJM)

9 APR 2020: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia (Journal of Thrombosis)
“The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.”

10 APR 2020: Incidence of thrombotic complications in critically ill ICU patients with COVID-19 (Thrombosis Research)
“The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.” 

10 APR 2020: Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans (medRxiv preprint)

12 MAY 2020: Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging (JACC Cardiovascular Imaging)
“Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.”

10 JUL 2020: Extrapulmonary manifestations of COVID-19 (Nature Medicine)
“Some examples of areas that require further attention include elucidation of the mechanism by which SARS-CoV-2 is disseminated to extrapulmonary tissues, understanding of the viral properties that may enhance extrapulmonary spread, the contribution of immunopathology and effect of anti-inflammatory therapies, anticipation of the long-term effects of multi-organ injury, the identification of factors that account for the variability in presentation and severity of illness, and the biological and social mechanisms that underlie disparities in outcomes.” 

5 MAY 2020: Acute limb ischaemia in two young, non-atherosclerotic patients with COVID-19 (Lancet)

14 MAY 2020: Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series (Annals of Internal Medicine)
“COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19”
article on the paper: Autopsies Indicate Blood Clots Are Lethal in COVID-19 (TheScientist) 

15 MAY 2020: COVID-19 update: Covid-19-associated coagulopathy (Journal of Thrombosis)

25 JUN 2020: Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series (Lancet)
“In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis.”

27 JUN 2020: Myocarditis in a 16-year-old boy positive for SARS-CoV-2 (Lancet)
“Paediatric patients reporting chest pain and other features suggestive of acute myocarditis—with or without respiratory symptoms—should, we believe, also be tested for SARS-CoV-2” 

3 JUL 2020: Complications from COVID-19 may depend on von Willebrand factor in the blood (EurekaAlert Press Release)
“As the researcher suggests, the replication of the virus stimulates the development of microdamage on vessel walls. In its response to this, the body releases von Willebrand factor into the blood, trying to ‘patch’ possible holes. As a result, the risk of thromboses increases. It is with this clotting that a significant part of the deaths from COVID-19 is associated.”

20 JUL 2020: Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System (JAMA Research Letter)
“Among 829 ICU patients, 29.4% had a thrombotic event (13.6% venous and 18.6% arterial). Among 2505 non-ICU patients, 11.5% had a thrombotic event (3.6% venous and 8.4% arterial).”

21 JUL 2020: Unexpected Features of Cardiac Pathology in COVID-19 Infection (Circulation Letter)
“We identify key gross and microscopic changes that challenge the notion that typical myocarditis is present in severe SARS-CoV-2 infection. We speculate on alternative mechanisms for cardiac injury that should be investigated to provide a better understanding of the cardiac manifestations of COVID-19.” 

 27 JUL 2020: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (JAMA Cardiology)

12 AUG 2020: SARS-CoV-2 and Stroke Characteristics: A Report from the Multinational COVID-19 Stroke Study Group (medRxiv preprint)
“We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients.”

25 AUG 2020: SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients (bioRxiv preprint)
“…these results suggest that a majority of patients could suffer long-term consequences of COVID-19 on cardiac function, and that even the mildest cases could cause permanent heart damage.”
Press Release (Gladstone Institutes)

11 SEP 2020: Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection (JAMA Cardiology)
“Of 26 competitive athletes, 4 (15%) had CMR findings suggestive of myocarditis and 8 additional athletes (30.8%) exhibited LGE without T2 elevation suggestive of prior myocardial injury. COVID-19–related myocardial injury in competitive athletes and sports participation remains unclear. Cardiac magnetic resonance imaging has the potential to identify a high-risk cohort for adverse outcomes”

18 NOV 2020: Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19 (Science)
“These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.”

20 AUG. 2021: SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19 (Bioscience Reports)
“Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.”

21 APR 2021: SARS-CoV-2 and Stroke Characteristics (Stroke)
“We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.” … “Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144 (37.8%) were asymptomatic at the time of admission for SARS-CoV-2 infection.”

29 JUN 2021: Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military (JAMA Cardiology)

6 AUG 2021: Cerebral venous sinus thrombosis after vaccination: the UK experience (Lancet)

23 AUG 2021: Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin (Cardiovascular Diabetology)
“Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.”

27 AUG 2021: Research finds Covid-19 spike protein binds to cells in the heart and could help to explain some effects of severe infection (press release University of Bristol)

25 SEP 2021: Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study (Lancet)
“A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19.” 

30 SEP 2021: Myocarditis after Covid-19 mRNA Vaccination (NEJM)

6 OCT 2021: One-year Risks and Burdens of Incident Cardiovascular Disease in COVID-19: Cardiovascular Manifestations of Long COVID (Nature preprint)
“our results provide evidence that risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial”

6 OCT 2021: Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel (NEJM) 
“highest in male recipients between the ages of 16 and 19 years, with a ratio of 1 in 6637.”

18 OCT 2021: Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings (J Korean Med Sci)
“We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later.” 

22 NOV 2021: Subclinical thrombotic thrombocytopenic purpura after vaccination with ChAdOx1 nCoV-19 (Blood Research)

23 NOV 2021: Acquired Aplastic Anemia in Immunocompetent Pediatric Patients with Asymptomatic COVID-19 Infection: A Case Series (blood)
“Severe aplastic anemia (SAA) has high morbidity and mortality, and timely diagnosis is needed for appropriate treatment. Multiple different viral infections have been known to cause acquired aplastic anemia. Data on all the sequelae of COVID-19 infection is still emerging, but it is plausible that COVID-19 infection may cause SAA.”

29 NOV 2021: Patients With Unexplained Dyspnea Post–Coronavirus Disease (JACC Heart Failure)
“Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.”

5 DEC 2021: Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval (medRxiv preprint)

6 DEC 2021: Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults (Circulation)

9 DEC 2021: Breathlessness in patients with long COVID may signal heart problems (ESC Press Release)
“A small study has suggested that COVID-19 patients who continue to be short of breath during physical activity one year after recovering from the infection may have suffered heart damage.”

14 DEC 2021: Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection (Nature Medicine)

15 DEC 2021: The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease (Clinical Science)
from Press Release: “A new study has shown how SARS-CoV-2 may contribute to severe microvascular damage seen in severely-ill COVID-19 patients by transforming human heart vascular cells into inflammatory cells, without infecting them.” 

16 DEC 2021: Myocarditis after vaccination against covid-19 (BMJ Editorial)

21 DEC 2021: 3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography (eLife)
Press Release:

27 DEC 2021: Risk of Myopericarditis following COVID-19 mRNA vaccination in a Large Integrated Health System: A Comparison of Completeness and Timeliness of Two Methods (medRxiv preprint)
”We identified additional valid cases of myopericarditis following an mRNA vaccination that would be missed by the VSDs search algorithm, which depends on select hospital discharge diagnosis codes. The true incidence of myopericarditis is markedly higher than the incidence reported to US advisory committees. The VSD should validate its search algorithm to improve its sensitivity for myopericarditis.”

25 DEC 2021: Risk of myocarditis following sequential COVID-19 vaccinations by age and sex (medRxiv preprint)

30 DEC 2021: Study uncovers unique stem cell trajectory in lungs damaged by COVID-19 and pulmonary fibrosis (MedXpress press release)
“This study offers a roadmap to understand how severely injured lungs can remodel and scar and provides a potential pathway to reverse the remodeling by targeting the abnormal stem cells differentiation.”

2 JAN 2022: Outcomes of patients with thromboembolic events following coronavirus disease 2019 AstraZeneca vaccination (Blood Coagulation & Fibrinolysis)

24 JAN 2022: Case Report: COVID-19 Vaccination Associated Fulminant Myocarditis (Front. Cardiovasc. Med.)
“Herein, we describe a novel finding of fulminant myocarditis (FM) in two subjects the day after administration of the first dose of the currently available inactivated SARS-CoV-2 vaccine (Vero cell). Cardiac magnetic resonance imaging revealed extensive myocardial edema and necrosis. A pathologic evaluation of the endocardial biopsy tissues revealed inflammatory cell (lymphocytes) infiltration and interstitial edema, myocyte necrosis, and focal areas of fibrosis.”

25 JAN 2022: Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus Vaccine (Annals of Internal Med)
“Despite a low absolute risk, there is an increased risk for carditis associated with BNT162b2 vaccination. This elevated risk should be weighed against the benefits of vaccination.”

7 FEB 2022: Long-term cardiovascular outcomes of COVID-19 (Nature Medicine)
In summary, using a national cohort of people with COVID-19, we show that risk and 12-month burden of incident cardiovascular disease are substantial and span several cardiovascular disease categories (ischemic and non-ischemic heart disease, dysrhythmias and others). The risks and burdens of cardiovascular disease were evident even among those whose acute COVID-19 did not necessitate hospitalization.” 

11 FEB 2022: Cardiac magnetic resonance findings in acute myocarditis after mRNA COVID-19 vaccination (Journal of Cardiology)
“We report the case of a 20-year-old previously healthy man who presented with fever and chest pain 2 days after the second dose of mRNA-1273 vaccine. Electrocardiogram and laboratory studies showed extensive ST-segment elevation accompanied by elevated cardiac biomarkers.”

15 FEB 2022: SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2 (bioRxiv preprint)
these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms.”

15 FEB 2022: Myocardial Injury Pattern at MRI in COVID-19 Vaccine–associated Myocarditis (Radiology)

15 FEB 2022: Surveillance of Myopericarditis following COVID-19 Booster Dose Vaccination in a Large Integrated Health System (medRxiv preprint)
We identified a rate of 9.1 cases of myopericarditis per 100,000 COVID-19 booster doses which is higher than prior estimates reported by the Vaccine Adverse Event Reporting System (VAERS). Myopericarditis occurs following COVID-19 booster vaccine and may be underreported by current surveillance methods.”

25 FEB 2022: A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications (Biochem J)
“Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.”

18 MAR 2022: Rapid resolution of severe pericardial effusion using anakinra in a patient with COVID-19 vaccine-related acute pericarditis relapse: a case report (European Heart Journal Case Reports)
“The patient was successfully treated with the recombinant interleukin-1 (IL-1) receptor antagonist anakinra, with full reabsorption of the pericardial effusion and an abrupt drop of the inflammatory markers within 72 hours.”

25 MAR 2022: Persistent Cardiac MRI Findings in a Cohort of Adolescents with post COVID-19 mRNA vaccine myopericarditis (Journal of Pediatrics)
“In a cohort of adolescents with COVID-19 mRNA vaccine-related myopericarditis, a large portion have persistent LGE abnormalities, raising concerns for potential longer-term effects.”

6 APR 2022: Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study (BMJ)
“The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.”

20 APR 2022: SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents (JAMA)
“Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar.”

9 MAY 2022: Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (preprint)
“Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC.”

11 MAY 2022: Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis (blood advances)
“These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients.”

17 MAY 2022: Amyloidogenesis of SARS-CoV-2 Spike Protein (Journal of American Chemical Society)
Med Xpress Press Release
“We have never seen such perfect, but scary, fibrils as these ones from the amyloid-producing SARS-CoV-2 spike protein and pieces thereof. The fibrils starting from the full-sized spike protein branched out like limbs on a body. Amyloids don’t usually branch out like that. We believe that it is due to the characteristics of the spike protein,” says Per Hammarström, professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University. … The researchers at LiU mixed amyloid-producing protein pieces from the spike protein together with these bodily substances in test tubes, and saw that the fibrin coagulate which was then produced could not be broken down in the usual way by plasmin. This newly discovered mechanism may lie behind the production of similar micro blood clots that have been observed in both serious and long-term COVID-19. Disturbed blood coagulation is also seen in many amyloid-related illnesses.”

23 MAY 2022: A multisystem, cardio-renal investigation of post-COVID-19 illness (Nature Medicine)
The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung involvement, hemostatic pathway activation and impairments in physical and psychological function. One in seven patients died or were rehospitalized, and two in three patients had additional outpatient episodes of secondary care, considerably higher than controls. Preventive therapy for post-COVID-19 syndromes and longer-term studies of prognosis are warranted.”

26 MAY 2022: SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2 (PLOS Pathogens)
“Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms.”

25 JUL 2022: Coronavirus spike protein activated natural immune response, damaged heart muscle cells (American Heart Association Press Release)
“Our data show that the spike protein from SARS-CoV-2 causes heart muscle damage.”

2 AUG 2022: Heart disease after COVID: what the data say (Nature)

1 OCT 2022: A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against COVID-19 (Vaccines)
“only spike protein but no nucleocapsid protein could be detected within the foci of inflammation in both the brain and the heart, particularly in the endothelial cells of small blood vessels. Since no nucleocapsid protein could be detected, the presence of spike protein must be ascribed to vaccination rather than to viral infection. The findings corroborate previous reports of encephalitis and myocarditis caused by gene-based COVID-19 vaccines.”

18 MAY 2023: Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis (preprint)
“Herein we describe our perspective that Long COVID is a continuation of acute COVID-19 pathology, whereby coagulopathy is the main driver of disease and can cause or exacerbate other pathologies common in Long COVID, such as mast cell activation syndrome and dysautonomia. Considering the SARS-CoV-2 spike protein can independently induce fibrinaloid microclots, platelet activation, and endotheliitis, we predict that persistent spike protein will be a key mechanism driving the continued coagulopathy in Long COVID. We discuss several treatment targets to address the coagulopathy, and predict that (particularly early) treatment with combination anticoagulant and antiplatelet drugs will bring significant relief to many patients, supported by a case study.”

JUN 2023: Long COVID: pathophysiological factors and abnormalities of coagulation (Trends in Endocrinology and Metabolism)
“These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.”

28 AUG 2023: SARS-CoV-2 spike protein induces endothelial inflammation via ACE2 independently of viral replication (Nature)
“In conclusion, our study describes ACE2 as a pivotal signalling protein in SARS-CoV-2 spike protein-mediated activation of pro-inflammatory signalling and endothelial cell inflammation. We demonstrate that rSP1 induces endothelial inflammation via ACE2 through processes that are independent of ACE2 enzymatic activity and viral replication. Our findings define a novel role for ACE2 in SARS-CoV-2-associated endotheliitis, which may be important in cardiovascular complications associated with COVID-19.”

1 SEP 2023: Cardiovascular autonomic dysfunction in “Long COVID”: pathophysiology, heart rate variability, and inflammatory markers (Front Cardiovascular Med)
“Dysautonomia in patients with Long COVID is multifactorial, and many of the autonomic symptoms can be understood by vagal dysfunction; the parasympathetic and sympathetic interactions involved still need to be extensively studied. Understanding cardiovascular autonomic dysfunction and the importance of association with inflammatory biomarkers in patients with Long COVID can contribute to more accurate diagnoses, better knowledge of the clinical presentation of the ANS pathway when reacting to an infectious disease, and better prognoses.”

25 SEP 2023: A Perspective on How Fibrinaloid Microclots and Platelet Pathology May be Applied in Clinical Investigations (Thieme Open Access)
Twitter Thread from Author:

27 SEP 2023: Duration of SARS-CoV-2 mRNA vaccine persistence and factors associated with cardiac involvement in recently vaccinated patients (Nature NPJ Vaccines)
“Cardiac ventricles in which vaccine was detected had healing myocardial injury at the time of vaccination and had more myocardial macrophages than the cardiac ventricles in which vaccine was not detected. These results suggest that SARS-CoV-2 mRNA vaccines routinely persist up to 30 days from vaccination and can be detected in the heart.”