Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids.

Sublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron variant BA.1 (B.1.1.529.1) to four repurposable drugs, Methylene blue (MB), Mycophenolic acid (MPA), Posaconazole (POS), and Niclosamide (Niclo) in post-exposure treatments of primary human airway cell cultures. MB, MPA, POS, and Niclo are known to block infection of human nasal and bronchial airway epithelial explant cultures (HAEEC) with the Wuhan strain, and four variants of concern (VoC), Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28), Delta (B.1.617.2) (Weiss et al., 2021, Murer et al., 2022). Our results here not only reinforce the broad anti-coronavirus effects of MB, MPA, POS and Niclo, but also demonstrate that the Omicron variant BA.1 (B.1.1.529.1) sheds infectious virus from HAEEC over at least 15 d, and maintains both intracellular and extracellular viral genomic RNA without overt toxicity, suggesting viral persistence. The data emphasize the potential of repurposable drugs against COVID-19.

Treatment of persistent COVID-19 in two B-cell-depleted patients with the monoclonal antibody Sotrovimab.

Background: Patients having undergone B-cell-depletion with anti-CD20-antibodies have a higher risk of mortality, delayed viral clearance and prolonged infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report two cases of patients with persistent coronavirus disease 2019 (COVID-19) in association with B-cell-depletion that were treated with the monoclonal antibody Sotrovimab. Case presentation: Both patients presented with chronic symptoms of COVID-19 such as dyspnea, fatigue, and chest pain. Nasopharyngeal swabs remained positive months after the initial infection with fluctuating cycle threshold (Ct) values around 30. Both patients received a single infusion with the monoclonal SARS-CoV-2 antibody Sotrovimab, which resulted in a rapid improvement of symptoms and inflammation markers as well as negative SARS-CoV-2 swabs. A follow-up after a month showed ongoing improvement of symptoms, persistent negative SARS-CoV-2 swabs, and positive serum antibodies. Conclusion: Infusion with the monoclonal SARS-CoV-2 antibody led to rapid improvement in two patients with persistent COVID-19 after B-cell depletion.

Successful treatment of prolonged COVID-19 with Bamlanivimab in a patient with severe B-Cell aplasia due to treatment with an anti-CD20 monoclonal antibody: A case report.

A 71-year-old female patient with B-cell depletion due to treatment with an anti-CD20 monoclonal antibody was admitted for worsening COVID-19. Overall, she had persistent viral shedding, worsening respiratory failure, and progressive pneumonia that did not improve despite dexamethasone and antibiotic therapy. After administration of bamlanivimab, a monoclonal antibody with high affinity for the receptor-binding domain of the SARS-CoV-2 spike protein, inflammatory markers rapidly decreased, SARS-CoV2 RT-PCR became negative, and the patient improved clinically and radiologically. In conclusion, we demonstrated successful treatment of prolonged COVID-19 in a patient with severe B-cell aplasia with a virus-neutralizing monoclonal antibody.