Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

Cremer, Sebastian; Jakob, Carolin E. M.; Berkowitsch, Alexander; Borgmann, Stefan; Pilgram, Lisa; Tometten, Lukas; Claßen, Annika Y.; Wille, Kai; Weidlich, Simon; Gruener, Beate; Dimmeler, Stefanie; Maßberg, Steffen; Rieg, Siegbert; Zeiher, Andreas M.

doi:10.1007/s00392-020-01769-9

Cited by 25 publications

(26 citation statements)

References 25 publications

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“…Our colleagues could show elevated markers of thrombo-inflammatory activation in patients with cardiovascular diseases and their prediction for a worse outcome in the population of the LEOSS registry [ 34 ], reinforcing the benefit of early or even pre-existing anticoagulation in these patients in line with our findings in the same population.…”

Section: Discussionsupporting

confidence: 83%

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

et al. 2021

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Aims Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. Methods and results We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). Conclusions Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease. Graphic abstract

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Section: Discussionsupporting

confidence: 83%

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

et al. 2021

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“…With respect to the COVID-19 situation, this is of course an absolutely obvious situation. Thrombo-inflammatory factors which even may become predictive markers for COVID-19 complications have been described by Cremer et al [ 46 ]. Other immune biomarkers, as taken together by Fouladseresht et al [ 47 ] have also been reported.…”

Section: Discussionmentioning

confidence: 99%

Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Wallukat

Hohberger

Wenzel

et al. 2021

Journal of Translational Autoimmunity

255

190

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Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ( f AABs) targeting G-protein coupled receptors (GPCR- f AABs) has been discussed to be involved. We, therefore investigated, whether GPCR- f AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR- f AABs that acted as receptor agonists. Some of those GPCR- f AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR- f AAB detection). Other GPCR- f AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR- f AABs identified in the blood of Long-COVID patients targeted the β 2 -adrenoceptor (β 2 - f AAB), the α 1 -adrenoceptor (α 1 - f AAB), the angiotensin II AT1-receptor (AT1- f AAB), and the nociceptin—like opioid receptor (NOC- f AAB). The negative chronotropic GPCR- f AABs identified targeted the muscarinic M 2 -receptor (M 2 - f AAB), the MAS-receptor (MAS- f AAB), and the ETA-receptor (ETA- f AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

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“…A retrospective cohort study including 288 confirmed COVID-19 patients also demonstrated that CVD with older and higher levels of troponin I (TnI), CRP, and creatinine were more prone to develop into severe or critically severe cases ( 22 ). Moreover, 2147 patients with COVID-19 were enrolled in European, patients with cardiovascular comorbidities displayed markedly higher levels of troponin and CRP, which were markers of myocardial injury and thrombo-inflammatory activation in the uncomplicated phase of COVID-19 ( 23 ). When infected by COVID-19, patients with underlying CVD were more likely to exhibit elevation of troponin T (TnT) levels, which was a high and markedly positive linear correlation with plasma high sensitivity CRP (hs-CRP) level ( 24 ).…”

Section: Crp and Covid-19mentioning

confidence: 99%

Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections

2021

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Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.

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Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

Cited by 25 publications

References 25 publications

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections

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