Efficacy and tolerability of Sotrovimab, Molnupiravir and Nirmatrelvir/Ritonavir for non-hospitalized patients at high risk for COVID-19: a retrospective, single-center analysis. (preprint)

Background The use of outpatient antiviral treatment for high-risk patients with coronavirus disease 19 (COVID-19) is crucial in preventing progression to severe COVID-19 and reducing hospitalization rates. Objective The main goal of this retrospective, single-center analysis was to assess the feasibility and potential clinical impact of an outpatient administration of various available antiviral agents including sotrovimab (SOT), nirmatrelvir/ritonavir (N/R), molnupiravir (MOL) to COVID-19 patients at high risk for disease progression. In addition, hospital admission rates between groups. side effects and subjective treatment effects were assessed. Methods We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606) or N/R (398/2606), patients were followed- up with regard to primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. Result A total of 2606 patients were treated at the outpatient clinic, of whom 420 were treated with SOT, 398 with N/R and 1788 with MOL. 10 patients (3.2%) who were treated with SOT were later hospitalized and 1 patient had to be admitted to the ICU. In comparison, 11 patients (0.8%) who received MOL were admitted to hospital (2 admissions to the intensive care unit (ICU). No hospital/ICU admission was registered for patients who received N/R. In contrast, 46 patients (14.3%) who received N/R reported strong to severe side effects, exceeding SOT with 2.6% of the patients (8 patients in total) and MOL with 5% (69 patients) reporting strong to severe side effects. A reduction in COVID symptoms after the medication administration was experienced by 43% (132 patients) in the SOT group, 43% (572 patients) in the MOL group and 67% (115 patients) in the N/R group, respectively. In over 60-year-olds and chronic kidney disease, no subjective symptom improvement is to be expected with MOL. Women have a 1.2 elevated chance of symptom improvement with treatment with MOL. Conclusion Hospitalization rates in high-risk patients who received SOT, MOL or N/R were low, particularly in patients who received N/R. All antiviral drugs were well tolerated, but side effects were more frequent in patients with N/R. However, N/R showed the greatest subjective treatment effect.

The Systemic Renin-Angiotensin System in COVID-19 (preprint)

Introduction: SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the “alternative” (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1–7.Methods Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I–II) and alt-RAS (angiotensins 1–7 and 1–5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1–7.Results Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (both p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor. ALT-S in severe COVID-19 increased with time (days 1–6: 0.12; days 11–16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (p < 0.001), but ACE concentrations were similar between groups and weakly correlated with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1–7 levels. ACE2 also predicted angiotensin 1–7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors.Conclusions Angiotensin II was elevated in severe COVID-19 but markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Prolonged COVID-19 Infection in a Patient with Multiple Sclerosis and Rituximab-Treatment (preprint)

We present a prolonged disease course in a 32-year old woman with COVID-19 and multiple sclerosis on rituximab-treatment for three years. The patient was admitted to the hospital for COVID-19 and had persistent fever, cough and radiologic bilateral lung opacities over the course of 29 days. After ineffective antibiotic treatment and the detection that she had no antibodies against SARS-CoV-2 convalescent plasma was administered with rapid recovery ensuing. While there is evidence convalescent plasma is not superior to placebo for COVID-19 in general its role in patients with B-cell depletion and COVID-19 remains to be examined further.

Successful treatment of intubation-induced severe neurogenic post-extubation dysphagia using Pharyngeal Electrical Stimulation in a COVID-19 survivor: a case report (preprint)

Background A significant portion of critically ill patients with COVID-19 are at high risk of developing ICU-acquired swallowing dysfunction (neurogenic dysphagia) as a consequence of requiring prolonged mechanical ventilation. Pharyngeal Electrical Stimulation (PES) is a simple and safe treatment for neurogenic dysphagia. Previously it has been shown that PES can restore safe swallowing in orally intubated or tracheotomised ICU-patients with neurogenic dysphagia following severe stroke. We report the case of a patient with severe neurogenic post-extubation dysphagia (PED) due to prolonged intubation and severe general muscle weakness related to COVID-19, which was successfully treated using PES.Case Presentation A 71-year-old female patient with confirmed SARS-CoV-2 infection developed neurogenic dysphagia following prolonged intubation in the ICU. To avoid aerosol generating procedures, her swallowing function was evaluated non-instrumentally as recommended by recently published international guidelines in response to the COVID-19 pandemic. Her swallowing function was markedly impaired and PES therapy was recommended. PES led to a rapid improvement of the post-extubation dysphagia (PED), as evaluated by bedside swallowing assessments using the Gugging Swallowing Screen (GUSS), Dysphagia Severity Rating Scale (DSRS) and diet screening using the Functional Oral Intake Scale (FOIS). The improved swallowing, as reflected by these measures, allowed this patient to transfer from the ICU to a non-intensive medical department five days after completing PES treatment.Conclusions PES treatment contributed to the restoration of a safe swallowing function in this critically ill patient with COVID-19 and ICU-acquired swallowing dysfunction. Early clinical bedside swallowing assessment and dysphagia intervention in COVID-19 patients is crucial to optimise their full recovery. Pharyngeal Electrical Stimulation may contribute to a safe and earlier ICU discharge of patients with ICU-acquired swallowing dysfunction. Earlier ICU discharge and reduced rates of re-intubation following PES can help alleviate some of the pressure on ICU bed capacity, which is critical in times of a health emergency such as the ongoing COVID-19 pandemic.

Scalable, rapid and highly sensitive isothermal detection of SARS-CoV-2 for laboratory and home testing (preprint)

Global efforts to combat the Covid-19 pandemic caused by the beta coronavirus SARS-CoV-2 are currently based on RT-qPCR-based diagnostic tests. However, their high cost, moderate throughput and reliance on sophisticated equipment limit widespread implementation. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative detection method that has the potential to overcome these limitations. Here we present a rapid, robust, highly sensitive and versatile RT-LAMP based SARS-CoV-2 detection assay. Our forty-minute procedure bypasses a dedicated RNA isolation step, is insensitive to carry-over contamination, and uses a hydroxynaphthol blue (HNB)-based colorimetric readout, which allows robust SARS-CoV-2 detection from various sample types. Based on this assay we have substantially increased sensitivity and scalability by a simple nucleic acid enrichment step (bead-LAMP), established a pipette-free version for home testing (HomeDip-LAMP), and developed a version with open source enzymes that could be produced in any molecular biology setting. Our advanced, universally applicable RT-LAMP assay is a major step towards population-scale SARS-CoV-2 testing.