Atrial fibrillation (AF) is the most common sustained arrhythmia and is a significant public health burden.1,2 Many mutations in ion-channel and non ion-channel structural genes are linked to AF especially in patients with family history and no risk factors.3 The pulmonary vein muscle sleeves are the main trigger for AF. 4 Many studies showed that pulmonary vein isolation (PVI) via catheter ablation is superior to medical therapy in decreasing all-cause mortality, hospitalizations and recurrence 5-7. Though it is still controversial, vagal denervation and targeting the major atrial ganglionated plexi (GP) have been reported by Pappone et al. to improve the outcome after PVI.8 GP ablation has been associated with QT prolongation and ventricular arrhythmias9. PVI affects the atrial GP, modifies the intrinsic cardiac autonomic nervous system and could lead to QT prolongation and lethal ventricular arrhythmias such as torsade de pointe and ventricular tachycardia.10In their study published in this issue of the Journal of Cardiovascular Electrophysiology, Chikata et. al investigated the effect of PVI on the QT interval in patients with paroxysmal AF, and identified associated predisposing factors . 11 This was a retrospective observational study of 117 patients (out of 280 patients who were screened) with paroxysmal AF who underwent PVI via cryoballoon, hotballoon and radiofrequency at Toyama Prefectural Center in Japan between January 2016 and June 2019. The authors assessed 12 lead electrocardiograms (ECGs) at baseline and after four hours, one day, one month and three months. At each evalulaion point, they included only patients with sinus rhythm and excluded those taking antiarrhythmic drugs, drugs known to prolong QT intervals, patients undergoing renal transplant or having electrolyte imbalances in order to eliminate possible confounding factors. They measured the QRS, heart rate, QT interval and calculated QTc using the Bazett, Fridericia, Framingham and Hodges formulas at each evaluation point. All patients underwent PVI under conscious sedation with the same anesthesia regimen. They performed Cavotricuspid isthmus line ablation only if the Cavotricuspid isthmus dependent atrial flutter was noted, and they did not perform any intentional GP ablation. The study showed that QTc interval calculated by Bazett formula and the Fridericia formula was significantly prolonged at each time point ,whereas that of the Framingham formula and the Hodges formula was significantly prolonged only in the acute phase. The authors attributed this discrepancy to how each formula correlates with heart rate (HR). Since PVI could lead to autonomic denervation, a reflex increase in heart rate can be expected especially during the acute phase following the procedure. Furthermore, the study showed that in the acute phase post PVI, women had significantly prolonged QTc interval as compared to their baseline and to men (P < 0.05).The authors explained that QTc calculated by the Bazzet formula is more prone to error especially at elevated heart rates seen post PVI. In the setting of tachycardia, the QTc can be expected to prolong since the R-R interval shortens to a greater extent than the QT. Hence, the Bazzet’s QTc formula will overcorrect and overestimate the prevalence of the QT interval at heart rate greater than 100 bpm, and linear regression methods to correct the QT interval (such as Hodges) are better for clinical use. Women are known to have a longer baseline QT interval and are more prone to develop torsade de pointe than men12. That could be explained by the hormonal effect on the expression of ion channels and by the difference in autonomic regulation between genders.13,14 Chikata at al show a possible association between gender and QT prolongation post PVI that might be explained by a difference in inflammatory response or a distinguished genetic predisposition found more frequently in women. Further investigation is warranted via prospective studies with larger sample size in the future to corroborate the findings especially with the relatively small sample size and the fact that it was a single center study.References:1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke . Aug 1991;22(8):983-8. doi:10.1161/01.str.22.8.9832. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.3. Feghaly J, Zakka P, London B, MacRae CA, Refaat MM. Genetics of Atrial Fibrillation. Journal of the American Heart Association . Oct 16 2018;7(20):e009884. doi:10.1161/jaha.118.0098844. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. The New England journal of medicine. Sep 3 1998;339(10):659-66. doi:10.1056/nejm1998090333910035. Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S. Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Circulation Arrhythmia and electrophysiology . Sep 2019;12(9):e007414. doi:10.1161/circep.119.0074146. Refaat MM, Ballout J, Mansour M. Ablation of Atrial Fibrillation in Congenital Heart Disease. Arrhythm Electrophysiol Rev. Dec 2017; 6 (4): 191-4.7. Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation . Mar 5 2002;105(9):1077-81. doi:10.1161/hc0902.1047128. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation . Jan 27 2004;109(3):327-34. doi:10.1161/01.cir.0000112641.16340.c79. He B, Lu Z, He W, et al. Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia. International journal of cardiology . Sep 20 2013;168(1):86-93. doi:10.1016/j.ijcard.2012.09.06710. Münkler P, Wutzler A, Attanasio P, et al. Ventricular Tachycardia (VT) Storm After Cryoballoon-Based Pulmonary Vein Isolation. The American journal of case reports . Sep 11 2018;19:1078-1082. doi:10.12659/ajcr.90899911. Chikata A. Prolongation of QT interval after pulmonary vein isolation for paroxysmal atrial fibrillation Journal of Cardiovascular Electrophysiology . 2020;12. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation . Sep 15 1996;94(6):1471-4. doi:10.1161/01.cir.94.6.147113. Chen YJ, Lee SH, Hsieh MH, et al. Effects of 17beta-estradiol on tachycardia-induced changes of atrial refractoriness and cisapride-induced ventricular arrhythmia. J Cardiovasc Electrophysiol . Apr 1999;10(4):587-98. doi:10.1111/j.1540-8167.1999.tb00716.x14. Huikuri HV, Pikkujämsä SM, Airaksinen KE, et al. Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. Circulation . Jul 15 1996;94(2):122-5. doi:10.1161/01.cir.94.2.122
To the editor,Following the online podcast recorded the 31 March 2020 by the International Committee of the American Thoracic Society Pediatrics Assembly and recently published in Pediatric Pulmonology1, we have interesting discussion with my international colleagues about the likelihood of acute bronchiolitis caused by SARS-CoV-2 infection in absence of RSV co-infection. Here, we report 2 cases of COVID-19 in infants < 3 months old admitted to our paediatric unit. The infants presented fever and neurological symptoms and after a short period, acute bronchiolitis.Case 1 : A term-born boy with unremarkable history was admitted to the emergency department with poorly tolerated high fever (38.8°C) and rhinitis. The parents, who had no history of asthma or allergy, showed clinical signs suggesting SARS-CoV-2 infection. RT-PCR for SARS-CoV-2 on a nasopharyngeal swab was positive for the father and the grandfather, who was hospitalized in the intensive care unit. Neurologic examination of the infant revealed lethargy and hypotonia with a bulging anterior fontanelle. The respiratory condition and clinical examination findings including hemodynamics were normal.The first blood test showed isolated lymphopenia (lymphocyte count 1.56 x109/L; normally 4-6x109/L) without modification of biological inflammatory parameters, as assessed by normal levels of C-reactive protein (CRP) and procalcitonin (PCT). Spinal fluid analysis, cytobacteriological urine analysis and blood culture were negative. RT-PCR of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for respiratory syncytial virus (RSV) and influenza virus (IV). The patient received fluid volume expansion(20 ml/Kg of 0.9% sodium chloride solution) together with antibiotic treatment (cefotaxime, amoxicillin and gentamicin at meningeal doses) for 24 hr, that was stopped with a positive RT-PCR test for SARS-CoV-2 and negative blood culture. Favourable clinical outcome was obtained shortly thereafter, allowing the infant to return home 2 days later.Ten days later, the child returned with acute bronchiolitis. Respiratory symptoms included polypnea, shortness of breath, wheezing and hypoxia (SpO2< 92 %). Lung ultrasonography revealed signs of interstitial syndrome with thickened and irregular pleural line associated with confluent B lines and small multifocal subpleural consolidations. RT-PCR for RSV and IV remained negative. Treatment associated supplemental oxygen and enteral nutrition for 6 days. A second episode of acute bronchiolitis occurred 1 month later, but a RT-PCR test for SARS-CoV-2 was negative. The chest X-ray was normal. The child remained hospitalized for 5 days with enteral nutrition support but did not require oxygen supplementation. Long-term treatment with inhaled daily corticosteroids (fluticasone) was introduced.Case 2 : A term-born eutrophic male with otherwise unremarkable neonatal history was referred for poorly tolerated high fever at age 2 months. Both parents had clinical signs of COVID-19 but were not tested (a member of the family had a positive test). The neurologic examination revealed lethargia and hypotonia in the child; the respiratory condition and clinical examination findings including hemodynamics were normal. The first blood test showed lymphopenia (lymphocyte count: 1.86 x109/L; normally 4-6x109/L)without modification of biological inflammatory parameters. Cytobacteriological examination of urine and blood culture were negative and spinal fluid analysis was not performed. RT-PCR testing of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for RSV and IV. The patient did not receive any antibiotics. On day 3 after admission, the respiratory condition progressively worsened, with retraction, wheezing, increased respiratory rate at 80/min and hypoxia (SpO2 < 92%) requiring supplemental oxygen together with enteral nutrition for 3 days. The chest X-ray was normal, and no lung ultrasonography was performed. The infant was returned to the emergency department 2 weeks later with a non-severe wheezing episode and was discharged at home.These 2 cases of COVID-19 in infants hospitalized for poorly tolerated high fever and neurological symptoms in whom acute bronchiolitis developed at a delay of 2 to 8 days suggest that SARS-CoV-2 infection may cause acute bronchiolitis in absence of viral co-infection such as RSV. Pneumonia is the most common diagnosis among symptomatic children with COVID-191. High-resolution CT scan usually shows ground-glass opacities or bilateral lung consolidations, especially in the periphery, and lung ultrasonography, as in our case 1, reveals signs of lung involvement. In contrast, to the best of our knowledge, acute bronchiolitis due to SARS-CoV-2 infection has never been reported. The wheezing episodes described in our patients were likely due to SARS-CoV-2 infection for the following reasons: first, RT-PCR tests for RSV and IV were always negative in both children, and second, the epidemic season for both viruses was over and the lockdown in France was still active at the time of the cases. Finally, previous study of virus repartition in positive respiratory samples from infants with acute bronchiolitis detected close to a 5% frequency of coronaviruses OC43 and 229E2. Moreover, a recent experimental model of COVID-19 in ferrets showed lung lesions compatible with bronchiolitis3. Our patients showed bronchiolitis symptoms several days after those of COVID-19, which may explain the lack of wheezing episodes reported in the literature. Case 2 was diagnosed with recurrent wheezing presumably due to SARS-CoV-2 infection. RSV as well as rhinovirus bronchiolitis is a risk factor for recurrent wheezing and asthma4,5,but little is known about the long-term impact of SARS-CoV-2 infection in lung function trajectory, which emphasizes the need to follow these children. Whether the infection in symptomatic or asymptomatic infants may predispose to recurrent wheezing or asthma remains to be determined.
Intense effort is underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely-researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.
Every host is colonized by a variety of microbes, some of which can protect their hosts from pathogen infection. However, pathogen presence naturally varies over time in nature, such as in the case of seasonal epidemics. We experimentally coevolved populations of Caenorhabditis elegans worm hosts with bacteria possessing protective traits (Enterococcus faecalis), in treatments varying the infection frequency with pathogenic Staphylococcus aureus every host generation, alternating host generations, every fifth host generation or never. We additionally investigated the effect of initial pathogen presence at the formation of the defensive symbiosis. Our results show that enhanced microbe-mediated protection evolved during host-protective microbe coevolution when faced with rare infections by a pathogen. Initial pathogen presence had no effect on the evolutionary outcome of microbe-mediated protection. We also found that protection was only effective at preventing mortality during the time of pathogen infection. Overall, our results suggest that resident microbes can be a form of transgenerational immunity against rare pathogen infection.
Sir, We would like to thank Sharma and colleagues for their interest in our recent study evaluating the effectiveness and safety of surgical interventions for Bartholin’s cyst or abscess.1Their response highlights the unique opportunity offered by randomised trials, and their syntheses into meta‐analyses, to assess patient reported outcomes. We would strongly encourage researchers to select, collect and report patient reported outcomes in future research evaluating interventions for Bartholin’s cyst or abscess.2The primary outcome should be the outcome of greatest therapeutic importance to the study’s prospective hypothesis. There is currently no consensus regarding the selection of outcomes and methods of definition or measurement for randomized trials evaluating interventions for Bartholin’s cyst or abscess.3 In the absence of a standardized approach, researchers have made arbitrary decisions when choosing among several important outcomes.4 It would be useful for healthcare professionals, researchers, and women with lived experience of Bartholin’s cyst or abscess to engage in a formal consensus development process to agree appropriate primary and secondary outcomes.3We agree the use of adjuvant antibiotics is an important consideration. They were not reported by any of the included trials.5We have no experience of marsupialization performed under local anaesthetic. In our opinion, this approach would need to be evaluated within a research setting. The recent COVID-19 pandemic would provide additional impetus to undertake this much needed research.James M. N. Duffy 1,2, Emma Kirk 3, BJG Illingworth 4, K Stocking 5,Marian Showell 61 Institute for Women’s Health, University College London, London, United Kingdom.2 King’s Fertility, Fetal Medicine Research Foundation, London, United Kingdom.3 Department of Obstetrics and Gynaecology, Royal Free London NHS Trust, London, United Kingdom.4 North West Anglia NHS Foundation Trust, Peterborough City Hospital, Peterborough, UK5 Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK6 Cochrane Gynaecology and Fertility Group, University of Auckland, Auckland, New Zealand.
Aim: We hypothesize that the efficacy of COVID-19 therapeutic candidates will be better predicted by understanding their effects at various points on a viral cell cycle, in particular, the specific rate constants, and that drugs acting independently of these specific discrete sites may not yield expected efficacy. We hypothesize that drugs, or combinations of drugs that act at specific multiple sites on the viral life cycle have the highest probability of success in the treatment of early infection phase in COVID-19 patients. Methods: Using a target cell limited model structure that had been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to show that combinations of therapeutics targeting specific rate constants have greater probability of efficacy and supportive rationale for clinical trial evaluation. Results: Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. We suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of viral shedding exceeds the effect on sparing epithelial cells from infection or impact on viral load AUC. Furthermore, the impact on reduction on duration of shedding may extend further in patients who exhibit a prolonged shedder phenotype. Conclusions: Our work highlights the use of model-informed tools to better rationalize effective treatments for COVID-19.
To the Editor,We read carefully the research letter “Is asthma protective of COVID-19?” by Carli et al recently published.1Important topic for asthma patients in the coronavirus disease 2019 (COVID-19) pandemic were considered, including that until recently weak evidence that patients with chronic respiratory disorders are at a lower risk of being infected or becoming severely ill with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Reflecting only about previous reports from China and Italy where asthma was underrepresented in COVID-19 patients, the authors accept the heterogeneous condition that it is asthma, speculating that T2-immunity, interferon-mediated immune responses and increased number of eosinophils in the airways could have a protective effect against COVID-19 severity.1The epidemiology of COVID-19 is changing rapidly with new data. More recent reports from the United States of America and from several European countries, in particular the United Kingdom (UK), states a higher asthma prevalence in patients with COVID-19, suggesting that asthma is more common in COVID-19 patients than it was previously reported in Asia and in the first European surveys.2Data from the UK Biobank, a large prospective case-control study, found an asthma prevalence of 17,9% in 605 COVID-19 hospitalized patients, mostly of them adults, surpassing the prevalence of asthma in the general population.3Besides that, in the OpenSAFELY Collaborative Study (UK), it was found a significant increased risk of severe CoViD-19 in patients with asthma, including death, in particular related with the recent use of oral corticosteroid (OCS).4 These findings can indicate an increased asthma severity and/or poor control and, in accordance with data from previous coronavirus outbreaks, that systemic corticosteroids were associated with a higher viral load.5We agree with Carli et al1 that further studies focused on asthma and its different phenotypes are needed to provide a better understanding of the impact of SARS-CoV-2 infection in patients with asthma.6 Nevertheless, for the moment, it seems crucial that patients with asthma do not stop their controller medication, that may lead to a higher risk of asthma exacerbations, increased OCS use and higher probability to emergency room access and hospitalization that represent themselves significant risk factors for coronavirus exposure and spread.In conclusion, according with the available data, patients with asthma must still be included in the high-risk groups for COVID-19 and more data are needed to understand the relationship between asthma and COVID-19.
Dear EditorI read with interest the paper by Xindong Qin et al. “Acupuncture for Recurrent Urinary Tract Infection in Women: A Systematic Review and Meta-Analysis1 in which the possible mechanisms for acupuncture are discussed. This article refers to one of my studies,2 but one of the study’s main findings has been omitted. We found a correlation between fewer urinary tract infections and a reduction in volume of residual urine in the women treated with acupuncture. This change in residual urine did not occur in the control group who were not treated with acupuncture. Residual urine or post-voided volume was measured by a bladder scan, in a hospital setting, and by a nurse who was blinded to participants group allocation. What is an empty Bladder? A post-voided volume above 30 ml, in otherwise healthy women, has been regarded as one of many potential risk factors for recurrent urinary tract infection.3Interestingly all women in our study had at baseline more than 30 ml of residual urine.2 After 6 months control this was reduced from 35,4 ml to 18.2 ml (P ≤ 0 .01) in the acupuncture group while no change was observed in the control group (35.5 vs 38.8ml). Furthermore, residual urine has been recognized as one of several potential risk factors for recurrent urinary tract infections in children 4 and in healthy postmenopausal women.5 It is therefore important that post-voided volumes are included in future studies on acupuncture as a prophylactic treatment for recurrent urinary tract infections. Finally, a question to the authors,1 on page 6, you write: “None of the studies reported the secondary outcomes of urinary bacteria culture, WBCs of urine dipstick, kidney function, markers of kidney damage, health-related quality of life or healthcare costs.” However, our study2 used a dipstick (Uricult) and we presented the number of infections with or without bacteriuria.Sincerely,Terje AlrækSchool of Health Sciences / NAFKAM, Department of Community Medicine, Kristiania University College / Faculty of Health Science, UiT The Arctic University of Norway 0107 Oslo, Norway / 9037 Tromsø, NorwayReferencesQin X, Coyle ME, Yang L, Liang J, Wang K, Guo X, Zhang AL, Mao W, Lu C, Xue CC, Liu X. Acupuncture for recurrent urinary tract infection in women: a systematic review and meta-analysis. BJOG 2020; https://doi-org.pva.uib.no/10.1111/1471-0528.16315Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the prevention of uncomplicated recurrent lower urinary tract infections in adult women. Am J Public Health 2002;92:1609–11Haylen BT. The empty Bladder. Int Urogynecol J Pelvic Floor Dysfunct. 2007 Mar;18(3):237-9. doi: 10.1007/s00192-006-0111-0Hoebeke P, Van Laecke E, Van Camp C, Raes A, Van De Walle J. One thousand video-urodynamic studies in children with non-neurogenic bladder sphincter dysfunction. BJU International (2001), 87, 575–580Stamm WE, Raz R. Factors contributing to susceptibility of postmenopausal women to recurrent urinary tract infections. Clin Infect Dis. 1999 Apr;28(4):723-5. doi: 10.1086/515209.
Transcatheter repair systems are becoming increasingly popular as a potential solution for high-risk and inoperable patients with mitral regurgitation. The Cardioband (Edwards Lifesciences, Irvine, California) is a transcatheter direct annuloplasty device, based on the concept of an undersized ring annuloplasty. We report a case of minimally invasive surgical explantation of a failed Cardioband device 21 months after its implantation. Intraoperatively, it was found that3 anchors of the Cardioband device were detached from the posterior annulus at P2. In this report, a “cut and unscrew” technique with some tips and tricks is presented for the removal of the device.
Sturmberg and Martin in 2020 argue that Universal Health Care (UHC) is mainly about financing and Primary Health Care (PHC) is about the right care at the right time to ensure health. They maintain the World Health Organisation (WHO) has recently sent the wrong message about the “pillars” of PHC in their relationship to UHC. An understanding of political economy is required in order to come to terms with the bases of PHC and the fundamentals of UHC, that dealing with inequities is not only an economic issue but fundamentally a political issue. Neoliberal decision making can enhance inequities in society. Two chronic health conditions, diabetes and multiple sclerosis are examples of conditions that lead to costly and debilitating consequences for patients but also lead to substantial economic costs in terms of lost workforce participation and lost productivity. These cases demonstrate the socio-political issues involved in the management of care for a number of illnesses. The upsurge of COVID–19 has placed an enormous strain on health and broader social and economic resources and challenged the pretext of UHC as health for all: substantial differences in equity and political commitment have emerged. Sturmberg and Martin argue that the joining of UHC and PHC needs leadership which involves local communities and resourcing. PHC is a changing system based on power relationships involving funders and the health community. In Australia as in several countries out of pocket costs have grown rapidly and have affected access for some groups to PHC and have challenged the pretext of equity in UHC. In the context of PHC and UHC we support the position that health for all goes beyond healthcare for all, to embrace healthy lives promoting wellbeing.
We want to thank Dr. Raveenthiran and Dr. Harky for their interest in our paper and in the topic of Marfans in the setting of pregnancy. Certainly, the reduction of adverse outcomes would be improved with early knowledge of Marfans syndrome in the mother which would aid in preparation and clinical consideration during the perioperative period, and, prior to pregnancy.
We are facing a new challenge: will imaging be the resolutive tool or will new mapping catheters and mapping system together with mathematical simulation solve this rebus? Clinical imaging will always remain attractive, particularly for elective cases and may add decisive information to best plan an ablation strategy: it represents a great tool in the hands of the electrophysiologist; however, as electrophysiologists, the imaging we should pursue is electrical – the depiction of the entire reentry circuit remains the sole proof of the target to ablate.
Long isolation period for suspected child cases was proposed based in one case. New evidence suggests that children are not as dangerous as they seemed, as a vehicle for this infection. We must cautious when making recommendations for a disease that affects millions of people, based on just one case.
In the search to rapidly identify effective therapies that will mitigate the morbidity and mortality of COVID-19, attention has been directed towards the repurposing of existing drugs. Candidates for repurposing include drugs that target COVID-19 pathobiology, including agents that alter angiotensin signaling. Recent data indicate that key findings in COVID-19 patients include thrombosis and endothelitis Activation of PAR1 (protease activated receptor 1), in particular by the protease thrombin, is a critical element in platelet aggregation and coagulation. PAR1 activation also impacts on the actions of other cell types involved in COVID-19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells. Vorapaxar is an approved inhibitor of PAR1, used for treatment of patients with myocardial infarction or peripheral arterial disease. Here, we discuss evidence implying a possible beneficial role for vorapaxar in the treatment of COVID-19 patients and in addition, other as-yet non-approved antagonists of PAR1 and PAR4.
The pandemic condition Coronavirus-disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Different clinical symptoms caused by involvement of organs outside the respiratory system have been also described. Interestingly, reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2 positive patients as such features outside the respiratory sphere, are rapidly emerging. However, knowledge about prevalence and pattern of skin involvement, time of onset, predilection, and its direct or indirect relation to SARS-CoV-2 is still limited. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors and describe differential diagnostic evaluations.