It became evident shortly after the initial outbreak of COVID-19 that not all individuals
are equally affected. Patients with preexisting cardiovascular disease and elder individuals
are at higher risk for a severe course of COVID-19.[1] Furthermore, the SARS-CoV-2 infection may not exclusively induce respiratory failure
but also compromise the cardiovascular system leading to myocardial infarction, myocarditis,
organ failure, and severe thrombosis-associated diseases such as deep vein thrombosis
and pulmonary embolism including thrombosis of the cerebral veins.[1]
[3] It has been recognized that SARS-CoV-2 utilizes the angiotensin-converting enzyme
2 receptor for cell entry consecutively altering physiologic functions of this receptor
and causing damage of the affected organs.
Coronaviruses are positive single-stranded, enveloped RNA viruses that can infect
both humans and animals. SARS-CoV-2 belongs to the beta coronavirus subfamily. It
is one of three members of this subfamily that are able to infect humans, causing
severe respiratory, gastrointestinal, or central nervous infections. SARS-CoV-2 has
close (79.6%) genetic similarity to SARS-CoV, the coronavirus that caused the SARS
pandemic in 2002/2003. The SARS-CoV-2 virus has around 50 to 200 nm in diameter. SARS-CoV-2
basically consists of four structural proteins including the S (spike), E (envelope),
M (membrane), and N (nucleocapsid) proteins. The N protein integrates the RNA, and
the other three proteins (S, E, M) built up the viral envelope. Moreover, the spike
protein shows a 96.0% genomic sequence identity with the SARS-related CoV RaTG13,
a bat coronavirus.[1] The spike protein mediates attachment to and entry into host cells. Besides that,
the spike is the component of the virus that defines host and tissue tropism and causes
antigenicity. Consequently, the spike protein is the target immunogen of most of currently
available COVID-19 vaccines.
The present issue of Haemostaseologie–Progress in Haemostasis focuses on COVID-19
and cardiovascular diseases. Early cardiovascular risk assessment of SARS-CoV-2-positive
patients is of utmost importance of patient care. The article by Zdanyte and Rath
summarizes the latest reports on aspects of systemic inflammatory reaction following
respiratory infection on elevation of pulmonary artery pressure and failure of the
right ventricle. Although the pathogenesis is unclear, impaired left and right ventricular
function in the early phase of COVID-19 is associated with poor clinical outcome.
Thus, a consequent and guideline-oriented therapy considering the underlying cardiovascular
dysfunction(s) is warranted in the treatment of COVID-19.[4]
Elevated cardiac biomarkers are common findings in patients with severe COVID-19 infection.[1] The assessment of troponin may improve risk prediction and timely therapy in COVID-19.
In our comprehensive review, Mizera et al present an overview of the incidence, potential
mechanisms, and outcome of acute cardiac injury in COVID-19. Acute cardiac injury
is associated with coagulation abnormalities in sepsis and altered immune response.
Further endothelial damage and inflammation (“endotheliitis”) has been recognized
as important feature of enhanced vascular dysfunction and thrombosis.[5] Specifically, sustained fulminant endothelial cell activation during severe COVID-19
causes markedly increased von Willebrand factor (VWF) levels,[6]
[7] and plasma VWF propeptide has been proposed as a biomarker in this setting.[8]
[9]
Patients with SARS-CoV-2 infection show an unusual wide spectrum of increased troponin
levels. Severe and prolonged troponin elevation is observed in SARS-CoV2-infected
humans in the absence of unstable coronary artery disease.[1] Thus, a direct myocardial inflammation either caused by systemic hyperinflammation
or a more directly virus-induced effect is discussed. Histopathological and imaging
(cardio-MR) abnormalities have been well documented in COVID-19 patients, although
the pathophysiology remains obscure. Greulich at al. discuss this important aspect
in their article.[10]
Myocarditis may be present even in asymptomatic people, a finding that has been recognized
by cardio-MR studies. Myocarditis is often associated with elevated troponin and affected
individuals are at enhanced risk for sudden cardiac death and rhythm disturbances.
Common cardiac arrhythmias in COVID-19 patients include sinus tachycardia, atrial
fibrillation (AF), ventricular tachycardia, ventricular fibrillation, atrioventricular
block, sinus nodal block, or QTc prolongation. AF is the most common heart rhythm
disorder. The importance of mindfulness for rhythm disturbances in care of COVID-19
is highlighted by Duckheim et al.[11]
Enhanced platelet activity has been described to contribute to thromboinflammation
in a variety of pathogen-related and “sterile” inflammatory diseases. In COVID-19
patients, platelet count differs between mild and serious infections. Patients with
mild symptoms have a slightly increased platelet count, whereas thrombocytopenia is
a hallmark of severe COVID-19 infections. Thrombocytopenia can be attributed to reduced
platelet survival and severe thrombotic events. The most recent findings of platelets
abnormalities in COVID-19 are summarized by Rohlfing et al.[12]
Hypercoagulability and vascular injury, which characterize morbidity in COVID-19,
are frequently observed in the skin. The current review article by Gawaz et al. describes
the clinical appearance of cutaneous vascular lesions and their association to COVID-19.
The authors emphasize that clinicians need to be aware that skin manifestations may
be the only and early symptom in SARS-CoV-2 infection.[13]
It is increasingly recognized that COVID-19 is associated with deep vein thrombosis,
pulmonary embolism, and thrombosis of cerebral veins. Although it is not unexpected
that severe viral infection triggers a prothrombotic disease state and development
of clinical overt thrombosis, the recognition of thrombotic events in COVID-19-affected
patients is increasing. In the present issue, two unusual case reports describe unexpected
thrombotic events which enhance the awareness of this threatening disease following
SARS-CoV-2 infection. Whether these case reports reflect just an association or a
pathophysiological important aspect of SARS-CoV-2 infection remains, however, obscure.[14]
[15]
We trust that the articles of this theme issue contribute to improve the awareness
of cardiovascular diseases in COVID-19 patients. Early assessment and consequent preventive
(e.g., antithrombotic regimens) or therapeutic strategies (e.g., intensified heart
failure treatment) and the awareness of threatening rhythm abnormalities are a critical
cornerstone in successful patient care of COVID-19. We are thankful to the authors
for their diligent contributions and also appreciate the substantial efforts of the
reviewers and of Dr. Elinor Switzer, who, working on backstage, greatly helped improving
the quality of submitted papers. Several other COVID-19 manuscripts scheduled for
this edition are still in revision or in preparation and will be published in an upcoming
issue of Hämostaseologie- Progress in Haemostasis.
