Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.

Interactions between Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Major Respiratory Viruses in Human nasal Epithelium.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with extensive non-pharmacological interventions, have profoundly altered the epidemiology of major respiratory viruses. Some studies have described virus-virus interactions, particularly manifested by viral interference mechanisms at different scales. Still, our knowledge of the mutual interactions between SARS-CoV-2 and other respiratory viruses remains incomplete. Here, we studied the interactions between SARS-CoV-2 and several respiratory viruses (influenza, RSV, hMPV, and hRV) in a reconstituted human epithelial airway model, exploring different scenarios affecting the sequence and timing of co-infections. We show that the virus type and the sequence of infections are key parameters of virus-virus interactions, having the impact of primary infections on the regulation of the immune response a determinant role in the outcome of secondary infections.

Treatments for COVID-19: Lessons from 2020 and new therapeutic options.

To face the COVID-19 pandemic, prophylactic vaccines have been developed in record time, but vaccine coverage is still limited, accessibility is not equitable worldwide, and the vaccines are not fully effective against emerging variants. Therefore, therapeutic treatments are urgently needed to control the pandemic and treat vulnerable populations, but despite all efforts made, options remain scarce. However, the knowledge gained during 2020 constitutes an invaluable platform from which to build future therapies. In this review, we highlight the main drug repurposing strategies and achievements made over the first 18 months of the pandemic, but also discuss the antivirals, immunomodulators and drug combinations that could be used in the near future to cure COVID-19.