Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy

Abstract

Background Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. Objectives The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. Methods The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. Results The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. Conclusions COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.

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

“…Regarding the investigation of poor outcome risk, our data highlight a quite benign course with only the 7% needing hospitalization and 2% requiring intensive-care-unit admission in HHT patients. These results are aligned with our preliminary report, centered on the first wave of pandemic spreading [ 14 ], and seem to provide further evidence that no significant difference is found on hospitalization rates and severe outcomes in HHT patients when compared to general population, despite the potential coexistence of chronic conditions due to HHT-related multisystemic involvement. Although two previous studies in Spanish population suggested a reduced severity of COVID-19 in HHT patients, the hypotheses advocated to explain this apparent weaker COVID-19 severity still lack confirmation as they are based on the HHT-damaged endothelial function and/or HHT-altered angiogenesis, which would impair the SARS-CoV-2 infection-driven macrophage inflammatory response, thus potentially protecting HHT patients from developing the cytokine storm [ 15 , 16 ].…”

“…The main strength of our study is that we analyzed, through a nationwide multicentric approach the impact of COVID-19 in HHT patients, collecting several clinical data from 605 patients, which represents an extremely high number given that this is a RD. As noted above, and in our first preliminary survey [ 14 ], estimates on hospitalization rates and outcome risks may suffer from significant recruitment bias, whereas such bias can be minimized, although not completely ruled out, by a nationwide multicenter design.…”

“…The first section included information concerning COVID-19 vaccination, eventual SARS-Cov-2 infection and re-infection, such as sign and symptom onset throughout the entire pandemic period and type (fever, coughing, headache, dyspnea, muscular pain, sense of tiredness/fatigue, diarrhea, sore throat, nasal obstruction, rhinorrhea, conjunctivitis, and gustative/olfactory sensory impairment), diagnostic procedures, clinical course and outcomes (resolution, need for hospitalization and ventilatory support, and death). Specific questions distinguished ascertained COVID-19 cases, based on laboratory-testing-based confirmation of diagnosis (namely, positive results on at least one of the following laboratory investigations: SARS-Cov-2-specific Polymerase Chain Reaction (PCR)-based molecular assay, SARS-Cov-2 antigen test on Nasopharyngeal/Oropharyngeal Swab [ 14 , 20 ], or anti-SARS-Cov-2 Antibody serological test) [ 21 ], from suspected cases, characterized by the subjective reporting of COVID-19-suggestive symptoms lacking molecular/serological confirmation. Subjects reported COVID19-suggestive symptomatology, without laboratory-test confirmation, were excluded from data analysis due to lack of data completeness.…”

“…Very few data are currently available concerning the prevalence and impact of SARS-CoV-2 infection in the HHT population, or the influence of COVID-19 on the systemic and rhinological clinical manifestations of HHT [ 14 – 16 ]. Nationwide epidemiological investigations were limited to an inquiry carried on in the Spanish population, assessing pneumonia-associated hospitalization [ 15 ], and to a multicenter survey in the Italian population performed by our national network, characterizing infection risk, phenotypic spectrum and need for intensive care [ 14 ], with a third study in the Spanish population based on a single-center recruitment [ 16 ].…”

A case report on uneventful anticoagulation and persistence of Type 1 Respiratory Failure post severe COVID-19 infection in a patient of Osler–Weber–Rendu syndrome

“…[ 11 ] COVID-19 infected HHT patients require prioritized intensive management, including invasive ventilation, compared to the general public. [ 12 ] Contrary to this, in a study by Marcos et al ,[ 13 ] 25 of 138 patients with HHT developed COVID-19 infection with a milder course without raised inflammatory markers and better clinical outcomes.…”