Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Management of epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients using pulsed dye laser and the effect of withholding treatment during the COVID pandemic.

Using a patient survey, pulsed dye laser (PDL) treatment of epistaxis for hereditary haemorrhagic telangiectasia (HHT) patients was evaluated after initial referral. Subsequently, due to the COVID pandemic, a natural experimental set-up allowed assessment of an enforced withdrawal of treatment. A total of 34 subjects were identified as undergoing PDL for HHT-related epistaxis. They were surveyed to look at the effectiveness of PDL treatment after initial referral and at the effect of delay to treatment during COVID on epistaxis and the associated quality of life. The survey also examined the comparison to other available treatments. Retrospective pre-COVID Epistaxis Severity Scores (ESS) were compared to post-COVID data to assess the effect of treatment withdrawal. The patients were then followed up after resumption of their treatment to assess the ensuing change in ESS. After initial referral, frequency and severity of epistaxis decreased. Fifty-six percent of patients experienced several bleeds per day before treatment, compared to 12% after. 88% of patients had episodes of epistaxis longer than 5 min, which was halved to 44% after treatment. Average ESS pre-COVID was 4.42 compared to 5.43 post-COVID delay, with a significant statistical difference (p = 0.02). On resumption of treatment, average ESS reduced to below pre-COVID levels at 4.39 after only 2 sessions. Seventy-six percent of patients found that withdrawal of PDL during COVID diminished their quality of life. PDL treatment of nasal mucosal telangiectasia reduces the frequency and duration of epistaxis. The ESS is reduced following treatment with PDL and quality of life subjectively improved.

Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations.

Hereditary haemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome is an autosomal dominant disorder affecting 1 in 8000 individuals. The eponym recognises the 19th-century physicians William Osler, Henri Jules Louis Marie Rendu and Frederick Parkes Weber who each independently described the disease. It is characterised by epistaxis, telangiectasia and visceral arteriovenous malformations. Individuals with HHT have been found to have abnormal plasma concentrations of transforming growth factor beta and vascular endothelial growth factor secondary to mutations in ENG, ACVRL1 and MADH4. Pulmonary artery malformations (PAVMs) are abnormal communications between pulmonary arteries and veins and are found in up to 50% of individuals with HHT. The clinical features suggestive of PAVMs are stigmata of right to left shunting such as dyspnoea, hypoxaemia, cyanosis, cerebral embolism and unexplained haemoptysis or haemothorax. The authors present the case of a 33-year-old woman presenting with progressive dyspnoea during the COVID-19 pandemic. She had a typical presentation of HHT with recurrent epistaxis, telangiectasia and pulmonary arteriovenous malformations. Although rare, PAVM should be considered in individuals presenting to the emergency department with dyspnoea and hypoxaemia. Delayed diagnosis can result in fatal embolic and haemorrhagic complications.

Diagnostic testing for SARS-CoV-2 infection in HHT patients: nasopharyngeal versus oropharyngeal swab.

On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic that still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction-based molecular assays for detecting SARS-CoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Based on current knowledge regarding the sensitivity of the molecular test, the highest positive detection rate is from lower respiratory tract specimens; alternatively it is possible to perform a nasopharyngeal or oropharyngeal swab. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing since it seems to have a greater sensitivity; however the procedure is not always free of complications and an epistaxis can occur. Among patients with greatest risk of massive nosebleed there are HHT patients. Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that leads to multiregional mucocutanous telangiectases and visceral arteriovenous malformations. Clinically, the presence of telangiectases in nasal mucosa is the cause of recurrent epistaxis. In HHT patients the execution of the nasopharyngeal swab can determine from little or no consequences to a massive epistaxis leading to the necessity of nasal packing generally followed by hospital admission. In HHT patients undergoing a diagnostic test to evaluate the SARS-CoV-2 infection status, especially in those patients with frequent epistaxis with a history of anemia and repeated hospitalizations, it is therefore advisable to perform an oropharyngeal swab. This, compared to the nasopharyngeal swab, exposes to a lower risk of severe nosebleeds related treatments, such as blood transfusions or invasive procedures. According to the risk-benefit assessment and based on our experience, we consider that, despite a lower diagnostic sensitivity, oropharyngeal swab is preferable to nasopharyngeal swab for the diagnosis of SARS CoV-2 infection in patients with HHT.

Angiogenesis, hereditary hemorrhagic telangiectasia and COVID-19.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant disease characterized by pathologic angiogenesis that provokes vascular overgrowth. The evidence about the influence of Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in patients with rare diseases is scarce. We aimed to know the prevalence of coronavirus disease 2019 (COVID-19) in HHT patients. The HHT pathogenic angiogenesis and endothelial injury in COVID-19 are discussed using data from RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry. RiHHTa is an open, multicenter, prospective, observational registry including adult patients with HHT. A 27-item survey that captured clinical data of admitted HHT patients for COVID-19 was distributed to all RiHHTa investigators from June 8th to June 24th 2020. Only one out of 1177 HHT patients was admitted for COVID-19 pneumonia. She is a 74 years-old woman with a pathogenic variant in ACVRL1 gene. Her clinical course did not involve mechanical ventilation or worsening epistaxis, and she was successfully discharged after two weeks. The endothelial damage and the consequent angiogenic process in COVID-19 patients deserve further investigation.