COVID-19 associated coagulopathy: Mechanisms and host-directed treatment.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is associated with specific coagulopathy that frequently occurs during the different phases of coronavirus disease 2019 (COVID-19) and can result in thrombotic complications and/or death. This COVID-19-associated coagulopathy (CAC) exhibits some of the features associated with thrombotic microangiopathy, particularly complement-mediated hemolytic-uremic syndrome. In some cases, due to the anti-phospholipid antibodies, CAC resembles catastrophic anti-phospholipid syndrome. In other patients, it exhibits features of hemophagocytic syndrome. CAC is mainly identified by: increases in fibrinogen, D-dimers, and von Willebrand factor (released from activated endothelial cells), consumption of a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13), over activated and dysregulated complement, and elevated plasma cytokine levels. CAC manifests as both major cardiovascular and/or cerebrovascular events and dysfunctional microcirculation, which leads to multiple organ damage. It is not clear whether the mainstay of COVID-19 is complement overactivation, cytokine/chemokine activation, or a combination of these activities. Available data have suggested that non-critically ill hospitalized patients should be administered full-dose heparin. In critically ill, full dose heparin treatment is discouraged due to higher mortality rate. In addition to anti-coagulation, four different host-directed therapeutic pathways have recently emerged that influence CAC: (1) Anti-von Willebrand factor monoclonal antibodies; (2) activated complement C5a inhibitors; (3) recombinant ADAMTS13; and (4) Interleukin (IL)-1 and IL-6 antibodies. Moreover, neutralizing monoclonal antibodies against the virus surface protein have been tested. However, the role of antiplatelet treatment remains unclear for patients with COVID-19.

[Reduction of stuttering through bronchodilatation with beta2 sympathomimetic drug formoterol]. / Zmírnování koktavosti bronchodilatací beta(2) sympatomimetikem formoterolem.

BACKGROUND: About 60 millions of people on the planet suffer from stuttering. Speech fluency disorder caused by stuttering (F98.5) was known already in the ancient civilizations of Egypt, Mesopotamia and China 7000 years ago (1). Despite of this the aetiology of stuttering has remained unknown and its causal treatment has not been possible. METHODS AND RESULTS: According to ICD-CD, 10th revision (2) ICD-10, stuttering belongs to "Other behavioral disorders including emotional ones with their beginning in childhood and adolescence" (F98) and it is related to Chapter V "Mental and behavioral disorders" (F00-F99). A multi-centre clinical study FORZAK-0503 (3), confirmed (4) hypothetical assumption (5) of the influence of pneumoobstruction of the tracheobronchal tree on the fluency disorder. Poetically spoken, the door opened towards causal reduction of speech disfluency accompanied often by tormentous stuttering (6). CONCLUSIONS: Besides publishing new findings on the aetiology of stuttering, it is needed to transfer stuttering under different classification and different identification code within ICD-10 (MKN-10).