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Introduction: Only little is known about COVID-19 in patients with asthma. There is no data on COVID-19 in patients with severe asthma or patients with asthma who are treated with monoclonal antibodies. Case Study: Here, we present the case of a severe eosinophilic asthmatic in whom benralizumab treatment, an anti-IL-5R monoclonal antibody, was initiated 2 years ago. Prior to benralizumab treatment, every viral infection had resulted in a prolonged course of oral corticosteroids (OCS). Since initiation of benralizumab, the patient has had good asthma control. Mid-March 2020, the patient developed high fever. Results: A SARS-CoV-2-PCR (nasopharyngeal swab) was positive. The patient's symptoms subsided after few days. No OCS was needed. The asthma control questionnaire 6-item scale worsened moderately in the week of the infection and returned to normal levels thereafter. The asthma control test, measuring longer term asthma control, showed no decline. Conclusion:The course of COVID-19 was very mild in this particular patient with severe eosinophilic asthma. So far, there is no evidence that would suggest a more severe course of COVID-19 in patients with asthma. It is worth noting, that prior to the initiation of benralizumab this patient had multiple exacerbations per year triggered by viral infections (4/ year), which all required OCS. Whilst only anecdotal, this case study provides the first evidence to support the current recommendation of continuing monoclonal antibodies in patients with severe asthma during the COVID-19 pandemic.

Immunomodulatory effects of oenothein B (1), a macrocyclic ellagitannin from various Onagraceae species, have been described previously. However, the mechanisms underlying the anti-inflammatory activity of 1 have not been fully clarified. The effects of 1 were investigated on inducible nitric oxide synthase, TLR-dependent and TLR-independent signal transduction cascades, and cytokine expression using murine macrophages (RAW 264.7). Compound 1 (10-60 μg/mL) reduced NO production, iNOS mRNA, and iNOS protein levels in a dose-dependent manner, without inhibition of iNOS enzymatic activity. It reduced the binding of the NF-κB p50 subunit to the biotinylated-consensus sequence and decreased nuclear p65 translocation. Gallic acid as a subunit of the macrocyclic ellagitannin 1 showed a far lower inhibitory activity. Nitric oxide production was reduced by 1 after stimulation using TLR2 (Pam2CSK4) and TLR4 (Kdo2) agonists, but this compound did not inhibit inducible nitric oxide synthesis after stimulation using interferon-gamma. IL-1beta, IL-6, and TNF-alpha mRNA synthesis was clearly reduced by the addition of 1. Oenothein B (1) inhibits iNOS after stimulation with LPS, TLR2, and TLR4 agonists via inhibition of TLR/NF-κB-dependent inducible nitric oxide and cytokine synthesis independent from IFN-gamma/JAK/STAT pathways. The full molecular structure of this macrocyclic ellagitannin seems to be required for its immunomodulatory actions.

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.

Amidst the current pandemic there is only little clinical evidence regarding COVID-19 infections in asthma patients. Chinese data [1, 2] suggests that asthma patients might not be of an elevated risk of severe infections. A recent article by Carli et al. [3] hypothesises that asthma might even have a protective effect in COVID-19 infections. It is important to point out, that this is purely theoretical. Eosinophils from healthy probands have an antiviral activity against respiratory syncytial virus and influenza virus, but not eosinophils collected from asthma patients [4]. Eosinopenia, alongside lymphopenia has been seen in COVID-19 patients [2]. Both eosinopenia and lymphopenia are more common in in patients with COVID-19 pneumonitis compared to patients with non-COVID-19 viral pneumonitis [5]. Azkur et al. attribute this to an overwhelming type 1 response [6].

The coronavirus disease 2019 (COVID-19), first described in late 2019, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In COVID-19, mortality is mainly caused by acute respiratory failure, whereas morbidity has been described for all major organ systems. 1 Verified secondary bacterial infections in COVID-19 are rare, although antimicrobials are commonly used empirically. 2 A case report of a 60-year-old obese male patient with epiglottitis and subsequent positive SARS-CoV-2 RT-PCR was published by Fondaw et al 3 . This patient had initially presented with dyspnea and stridor and had to undergo emergency cricothyroidotomy for acute epiglottitis. The initial SARS-CoV-2 RT-PCR was negative, but on day two the chest X-ray showed signs consistent with COVID-19 pneumonitis and a repeat test confirmed COVID-19. The patient's condition improved, and he could be weaned off the ventilator on day seven.Here, we present a second case of likely COVID-19associated epiglottitis. | CASE REPORTA 29-year-old man without pre-existing medical conditions tested COVID-19 positive after having headache, fatigue, and mild rhinitis. Within a week, his COVID-19 symptoms improved. After an asymptomatic period of 12 days, the patient developed throat pain. He was referred to the Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) Emergency Department at Helsinki University Hospital due to respiratory distress and muffled voice three weeks after the first symptoms associated with COVID-19 infection. His general health status was good, and vital signs were stable. Nasofiberoscopy showed a hyperemic epiglottis that was swollen asymmetrically. Yellowish, pus-like fluid existed in

Dupilumab is a monoclonal antibody against the IL‐4 receptor alpha which has shown efficacy in T2 high severe asthmatics in phase 3 randomized controlled trials. The purpose of this real‐life study is to demonstrate the real‐life effectiveness of dupilumab in Austrian severe asthma patients. We retrospectively analyzed all patients receiving dupilumab at our severe asthma clinic. Thirteen patients have so far received dupilumab at our center. The primary outcome, asthma control questionnaire 6‐item scale at 2 weeks, improved by 0.57 points (p = .014), which is statistically and clinically significant. Similarly, the asthma control test at 4 weeks improved by 3.91 points (p = .024), also statistically and clinically significant. Improvements in forced expiratory volume in 1 s at 2 weeks were neither statistically, nor clinically significant. Improvements at 4 weeks (+220 ml, p = .041), and 3 months (+229 ml, p = .006), were statistically significant and clinically borderline significant. No severe adverse events or hypereosinophilia were observed. No adverse events led to treatment discontinuation. Most patients (85%) had previously received monoclonal antibody treatment for severe asthma. Previous monoclonal antibody treatment had been discontinued in these patients due to a lack of clinical response. Dupilumab is effective and safe in Austrian real‐life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti‐immunoglobulin E or anti‐IL5/IL5R monoclonal antibody treatments or do not adequately respond to these.

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