Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients.

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT05650905.

Efficacy of Sotrovimab (SOT), Molnupiravir (MOL), and Nirmatrelvir/Ritponavir (N/R) and Tolerability of Molnupiravir in Outpatients at High Risk for Severe COVID-19.

OBJECTIVE: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. 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 regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. RESULT: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0-1.5). CONCLUSION: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R.

Comparison of clinical characteristics among patients infected with alpha vs. delta SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone different molecular changes, sprouting genetic variants of the original wildtype. Clinical comparisons between patients infected with alpha versus delta are scarce. METHODS: In this retrospective observational study, adult patients hospitalized with coronavirus disease 2019 (COVID-19) due to confirmed SARS-CoV­2 alpha or delta infection were included. Patient characteristics, virologic and laboratory parameters, as well as the clinical course were compared in patients infected with alpha vs. delta variants. RESULTS: A total of 106 patients infected with alpha and 215 patients infected with delta were included. Patients infected with the delta variant were admitted to hospital earlier after symptom onset (6 vs. 7 days, p < 0.001). Blood levels of C­reactive protein (43.3 vs. 62.9 mg/l, p = 0.02) and neutrophil count (3.81 vs. 4.53 G/l, p = 0.06) were lower in delta patients. Furthermore, at hospital admission cycle threshold (CT) values were significantly lower in patients infected with the delta variant (22.3 vs. 24.9, p < 0.001). Patients infected with the delta variant needed supplemental oxygen less often during disease course (50% vs. 64%, p = 0.02). Furthermore, there was a statistically non-significant trend towards a lower ICU admission rate among delta patients (16% vs. 24%, p = 0.08) CONCLUSION: Patients diagnosed with the delta variant were admitted to the hospital earlier, had a less severe course of disease and a higher viral replication on admission. This may provide a window of opportunity for antivirals in the hospital setting.