Impact of COVID-19 on patients with AATD
According to the IMCA1 study of the EARCO Clinical Research Collaboration
Clinical Research Collaborator of the European Respiratory Society (ERS).
EARCO
It is an international scientific network committed to the promotion, research and education in alpha-1 antitrypsin deficiency.
Its main objective is to create an international database that includes demographic and clinical data of AATD patients.
In this way, it can provide real-world longitudinal data on individuals with this disease.
Alpha 1 deficiency makes patients more vulnerable to external agents
Patients with severe alpha-1 antitrypsin deficiency (AATD) are at increased risk of developing chronic and progressive lung disease, particularly panlobular emphysema.
The pathogenesis is considered to be an imbalance between the destructive proteolytic load resulting from inhaled proinflammatory factors and the alteration of defenses that occurs in AATD.
How does COVID-19 impact AATD patients?
Alpha-1 antitrypsin (AAT) primarily inhibits neutrophil elastase, but it also acts on chymotrypsin, cathepsin G, and proteinase 3.
AAT is a potent anti-inflammatory and immunomodulator, modulating actions that inhibit interleukin-6, which is strongly implicated in the pathogenicity of SARS-CoV-2.
It is possible that a protease-antiprotease imbalance may play a central role in the pathogenicity and virulence of SARS-CoV-2 and, consequently, individuals with AATD may have a worse prognosis.
The increased risk of COVID-19 may be a consequence of worsening lung function and impaired lung defenses due to the inflammatory cytokine storm associated with COVID-19.
How was this study carried out?
The EARCO Clinical Research Collaboration sought, early in the pandemic, to estimate the risk posed by COVID-19 for patients with severe AATD.
Anonymous data on all known cases of COVID-19 in patients with severe AATD in participating countries were collected in a database to identify and rank risk factors with an adverse outcome.
This study included patients older than 18 years with severe AATD PiZZ, PiSZ genotype or rare variants with an equivalent serum AAT level <60 mg/dl (<11 μmol/L).
Results
- The diagnosis of COVID-19 was based on a compatible clinical presentation (± a positive confirmatory polymerase chain reaction test).
- Subjects were identified by EARCO reference centers.
- Details of baseline patient characteristics and outcome, including hospitalization, treatment, mortality, and spirometry (from historical records and post-COVID-19 measurements) were collected.
- Patients who were not admitted to the hospital were evaluated by telephone contact and their data was obtained from hospital records.
General criteria
- 105 patients (65 men, 61%) were identified.
- In 21 centers in 10 countries.
- With a mean (SD) concentration of AAT of 32.8 (19.6) mg/dl.
- Mean age (SD) of 51.3 (12.2) years.
- A baseline FEV1% predicted 63.4% (31.0) (available in 93 patients).
- PiZZ:PiSZ genotype distribution (or equivalent severity of deficiency), 81:24.
- Pulmonary emphysema evidenced by CT was present in 66 (63%) patients and bronchiectasis in 5 (4.7%).
- 14 patients (14%) were receiving intravenous AAT replacement therapy.
- Nonrespiratory comorbidities were present in 36 (34%) patients (19 [18%] hypertension, 4 [3%] diabetes, 12 [11%] liver disease, 2 [2%] renal disease, and 3 [3%] cardiovascular disease).
Hospitalization of patients with AATD
The impact of COVID-19 on patients with AATD
Hospitalization occurred in 32 (31%) patients and 5 (4.8%) required admission to intensive care.
Poor evolution was more frequent in the PiZZ group (29 patients, 35.8%) than in the PiSZ group (4 patients, 16.6%), although not significant (p=0.076). Four (3.8%) deaths occurred, all of them in PiZZ patients.
In most of our patients, COVID-19 was not associated with mortality.
Patients generally recovered, even with pre-existing severe lung disease or after hospitalization.
As in the general population and in subjects with usual COPD without AATD, nonrespiratory comorbidities were more strongly associated with poor outcome than genotype, baseline FEV1, or oxygen saturation.
Mortality occurred only in PiZZ patients who also demonstrated a reduction in predicted FEV1%, suggesting accelerated disease progression in these patients.
Consequently, patients with severe AATD are recommended to continue using effective protective measures against COVID-19.
Conclusions
Covid 19 is a risk factor for patients with Alpha 1 Antitrypsin Deficiency
The results of this study provide information on the natural course of COVID-19 in AATD patients, prior to the availability of the SARS-CoV-2 vaccine, against which future comparisons can be made, and which provides a clinical context for the evidence. indirect evidence of AATD as a risk factor in COVID19.
Source Puv Med Eur Respir J
