Background: Epidemiologic studies have reported that the geographical distribution of the prevalence of allelic variants of serine protein inhibitor-A1 (SERPINA1) and severe cases of COVID-19 were similar. Methods: A multicenter, cross-sectional, observational study to evaluate the frequency of alpha-1 antitrypsin deficiency (AATD) in patients with COVID-19 and whether it was associated with having suffered severe COVID-19. Results: 2022 patients who had laboratory-confirmed SARS-CoV-2 infection. Mutations associated with AATD were more frequent in severe COVID versus non-severe (23% vs. 18.8%, p = 0.022). The frequency of Pi*Z was 37.8/1000 in severe COVID versus 17.5/1000 in non-severe, p = 0.001. Having an A1AT level below 116 was more frequent in severe COVID versus non-severe (29.5% vs. 23.1, p = 0.003). Factors associated with a higher likelihood of severe COVID-19 were being male, older, smoking, age-associated comorbidities, and having an A1AT level below 116 mg/dL [OR 1.398, p = 0.003], and a variant of the SERPINA1 gene that could affect A1AT protein [OR 1.294, p = 0.022]. Conclusions: These observations suggest that patients with AATD should be considered at a higher risk of developing severe COVID-19. Further studies are needed on the role of A1AT in the prognosis of SARS-CoV-2 infection and its possible therapeutic role.

Medical research is progressing to clarify the full spectrum of sub-acute and long-term effects of the post-COVID-19 syndrome. However, most manuscripts published to date only analyze the effects of post-COVID-19 in patients discharged from hospital, which may induce significant bias. Here, we propose a pioneering study to analyze the single and multiple associations between post-COVID-19 characteristics with up to 6-months of follow-up in hospitalized and non-hospitalized COVID-19 patients. The cohort study was conducted from May to October 2020 at the University Hospital Virgen de la Nieves, the leading hospital assigned for patients with COVID-19 in Granada, Spain. A total of 372 and 217 patients—with 217 and 207 included in the first and second follow-up visits—were referred 2 and 6 months after diagnosing COVID-19, respectively. We find out that post-COVID-19 clinical and mental health impairment symptoms are correlated with patient gender. Logistic adjustments showed strong statistically robust single and multiple associations of demographic, clinical, mental health, X-ray, laboratory indices, and pulmonary function variables. The functional lung tests are good predictors of chest CT imaging abnormalities in elderly patients. Bilateral lung involvement, subpleural reticulum, ground-glass opacity, peripheral lung lesions, and bronchiectasis were the most common findings of the high-resolution computed tomography images. Non-hospitalized patients suffer more severe thromboembolic events and fatigue than those hospitalized.

SARS-CoV-2 virus infects organs other than the lung, such as mediastinal lymph nodes, spleen, and liver, but, to date, metabolic imaging studies obtained in short-term follow-ups of patients hospitalized with severe COVID-19 infection are rare. Our objective was to evaluate the usefulness of [¹⁸F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of the findings with clinical prognostic markers. The prospective study included 20 patients with COVID-19 pneumonia (November 2020–March 2021). Clinical and laboratory test findings were gathered at admission, 48–72 h post-admission, and 2–3 months post-discharge, when [¹⁸F]FDG-PET/CT and respiratory function tests were performed. Lung volumes, spirometry, lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. Volumetric [¹⁸F]FDG-PET/CT results were correlated with laboratory and respiratory parameters. Eleven [¹⁸F]FDG-PET/CT (55%) were positive, with hypermetabolic mediastinal lymphadenopathy in 90.9%. Mediastinal lesion’s SUVpeak was correlated with white cells’ count. Eleven (55%) patients had impaired respiratory function, including reduced DLCO (35%). SUVpeak was correlated with %predicted-DLCO. TLG was negatively correlated with %predicted-DLCO and TLC. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [¹⁸F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.

Respiratory function deficits are common sequelae for COVID-19. In this study, we aimed to identify the medical conditions that may influence lung function impairment at 12 months after SARS-CoV2 infection and to analyze the role of alpha-1 antytripsin (AAT) deficiciency (AATD). A cohort study was conducted on hospitalized COVID-19 pneumonia patients in Granada (Spain) during the first infection wave who were referred to a post-COVID-19 hospital clinic. The patients were monitored with three follow-up visits from May 2020 to May 2021. Previous medical history, hospital admission data, baseline parameters and physical examination data were collected at the first visit. Pulmonary function tests were performed at 6 and 12 months together with the determination of AAT level and AATD genotype. After 12 months, 49 out of 157 patients (31.2%) continued to have lung function impairment. A multivariate analysis showed a statistically significant association of lung function impairment with: higher Charlson index; pneumonia with a central and/or mixed distribution; anemia on admission; time in intensive care; need for corticosteroid boluses; abnormal respiratory sounds at 6 months; elevated lactate dehydrogenase at 12 months; abnormal AAT; and MZ genotype. Our results suggest that these medical conditions predispose COVID-19 patients to develop long-term lung function sequelae.

Evaluation of the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of findings with clinical prognostic markers. Prospective study included 20 patients admitted to hospital with COVID-19 pneumonia between November 2020 and March 2021. Clinical and laboratory test findings were gathered at admission, 48-72h post-admission, and 2-3 months post-discharge. [18F]FDG-PET/CT and respiratory function tests were performed at 2-3 months post-discharge. Lung volumes (TLC), spirometry (FVC, FEV1), lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. PET/CT images were qualitatively and semi-quantitatively interpreted. Volumetric [18F]FDG-PET/CT results were correlated with laboratory test and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive. The main finding was hypermetabolic lymphade-nopathy in the mediastinum (90.9%). SUVpeak of the target mediastinum lesion was correlated with neutrophil and lymphocyte counts. Eleven (55%) patients had impaired respiratory function, most frequently a reduced DLCO (35%). SUVpeak was positively correlated with %predict-ed-DLCO values. Pulmonary TLG was negatively correlated with %predicted-DLCO and TLC values. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.