Could biological disease modifying anti rheumatic drugs (bDMARDs) and small molecules have a key role in preventing COVID-19 infection?

Background: The clinical manifestations of COVID-19 infection are very heterogeneous. Rheumatic patients should be more susceptible to develop severe forms of COVID-19 pneumonia due to an unbalanced immune response and treatment immunodepressants (disease modifying anti rheumatic drugs-DMARDs). Aims and objectives: To investigate if the chronic use of biological DMARDs and small molecules may increase the susceptibility to COVID-19 and to developing severe disease. Method(s): We studied 43 consecutive patients on bDMARDs or small molecules from March 2020 to January 2022. Data collection included: rheumatic diagnosis, comorbidities, smoking history and COVID-19 clinical course according to MEWS (modifying early warning score) in 4 stages: 0=no symptoms at all;no hospitalization;1=not complicated disease with mild or non-specific symptoms;no hospitalization;2=mild pneumonia with clinical and/or radiological diagnosis, without any signs of severity;no hospitalization;3=severe pneumonia with respiratory failure with need of hospitalization;4=hospitalization in ICU or sub-ICU. Result(s): 30 patients (69.8%) got COVID infection: 26 were not hospitalized (MEWS 0=3.3%;1=70%;2=13.3%);of the four patients that required hospitalization, none was intubated. Hospitalized patients were obese and had hypertension, and 3 had a positive smoking history. Patients taking TNF-inhibitors compared to other treatment were not at major risk of COVID-19 infection (p=0.041). Conclusion(s): Rheumatic patients taking bDMARDs or small molecules appear more susceptible to contract SARSCoV-2 infection, but the development of severe forms appears to be rare.

Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.

This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.