ABSTRACT
Background: Interruption of GM-CSF signaling leads to Pulmonary Alveolar Proteinosis (PAP), occasionally to lung infections and relates to the impaired ability of lung macrophages to catabolize phagocytized surfactant and handle microbes. COVID-19 is associated with worse prognosis in lung disorders. We hypothesized that PAP patients would be at increased risk for COVID-19 and poor outcome. Aim and objectives: This multi-center, retrospective, European study aimed to investigate prevalence and clinical consequences of COVID-19 in PAP and the impact of iGM-CSF treatment on hospitalization or death. Method(s): All patients with PAP and COVID-19 diagnosed and followed-up in 11 referral European centers from January 24th 2020 to August 31st 2021 were included. Prevalence, clinical course and outcome were investigated. Result(s): COVID-19 developed in 34/255 (13.3%) of patients, mostly adults (91.2%), all with autoimmune (a)PAP;all patients were infected before the preventive option of vaccination was available;11 (35.5%) were hospitalized, of whom almost half were in the ICU;3 (27%) of hospitalized patients either died or underwent lung-transplant;these three patients had worse DLCO% predicted (p=0.019) and had more often arterial hypertension (AH) (p=0.012), and a smoking history (p=0.002). All patients with mild disease treated at home survived. Among children, 3 developed COVID-19 with good outcome. Conclusion(s): PAP patients experienced similar rates of COVID-19 with the general population but increased rates of hospitalizations and deaths, underscoring the vulnerability of this population and the necessity of preventive measures to avoid infection. If infected, secondary prophylaxis with monoclonal antibodies and the impact of iGM-CSF must be considered.
ABSTRACT
The clinical manifestations of COVID-19 are heterogeneous: 46.4% of patients admitted into hospital reported to have at least one comorbidity. Comorbidities such as COPD, diabetes, hypertension and malignancy predispose patients with Covid-19 to adverse clinical outcomes. Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder caused by pathological mutation(s) in the SERPINA1 gene resulting in an imbalance in proteinase activity which may lead to premature emphysema and COPD. Our aim was to investigate whether people with severe AAT deficiency (AATD) have an increased risk of (severe) COVID-19 infection. We collected data on COVID-19 symptoms, laboratory-confirmed infection, hospitalization and treatment by means of a telephone survey, directly administered to Italian severe AATD subjects in May 2020. We then compared our findings with data collected by the Istituto Superiore di Sanità on the total population in Italy during the same period. We found an higher frequency of SARS-CoV-2 infection in our cohort (3.8%) compared to national data regarding infection, thus giving severe AATD a relative risk of 8. 8 (95%CI 5.1-20,0; p<0.0001) for symptomatic SARS-CoV-2 infection. Moreover, the relative risk (RR) was higher in AATD patients with pre-existing lung diseases (RR 13.9; 95%CI 8.0-33.6; p<0.001), but with a similar death rate (1 in 8, 12.5%) compared to the general population (13.9%; RR 0.9). These preliminary findings highlight the importance of close surveillance in the spread of COVID-19 in patients with severe AATD and underlines the need for further studies into the role of the antiprotease shield in preventing SARS-Cov-2 infection.