The natural killer cell-associated rs9916629-C allele is a novel genetic risk factor for fatal COVID-19.

The severity of COVID-19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA-E- (HLA-E*0101/0103), FcγRIIIa- (FcγRIIIa-158-F/V), and NKG2C- (KLRC2wt/del ) receptor, were associated with severe COVID-19. Recently, the rs9916629-C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro-inflammatory CD56bright NK cells. We investigated whether the rs9916629-C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID-19. We included 1042 hospitalized surviving and 159 nonsurviving COVID-19 patients as well as 1000 healthy controls. rs9916629-C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA-E*0101/0103, FcγRIIIa-158-F/V, and KLRC2wt/del variants were also determined. The presence of the rs9916629-C allele was a risk factor for severe and fatal COVID-19 (p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID-19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa-158-V/V (p < 0.006) and in older patients expressing the KLRC2del variant (p < 0.003). Thus, patients with the rs9916629-C allele have a significantly increased risk for fatal COVID-19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID-19 patients.

The effect of early remdesivir administration in COVID-19 disease progression in hospitalised patients.

BACKGROUND: Antiviral drugs have become crucial in managing COVID-19, reducing complications and mortality. Remdesivir has emerged as an effective therapeutic drug for hospitalized patients at risk of disease progression, especially when alternative treatments are infeasible. While the recommended treatment duration of remdesivir extends up to 7 days post-symptom onset, this study examines how early remdesivir administration impacts clinical outcomes. METHODS: We conducted a retrospective analysis using clinical data from consecutively PCR confirmed SARS-CoV­2 adult patients (≥ 18 years) who received remdesivir during their hospitalization at the department of infectious diseases, Klinik Favoriten in Vienna. The data covered the period from July 1, 2021, to April 31, 2022. Patients were divided into two groups based on the timing of remdesivir administration: an early group (0-3 days since symptom onset) and a late group (≥ 4 days since symptom onset). The primary outcome was in-hospital disease progression, assessed using the WHO COVID-19 Clinical Progression Scale (≥ 1 point increase). Multivariable logistic regression, adjusted for age, sex, SARS-CoV­2 variant, and COVID-19 vaccination status, was used to assess clinical outcomes. RESULTS: In total 219 patients were included of whom 148 (67.6%) were in the early group and 71 (32.4%) were in the late group. The average age was 66.5 (SD: 18.0) years, 68.9% of the patients were vaccinated, and 72.6% had the Omicron virus variant. Late remdesivir administration was associated with a significantly higher probability of needing high-flow oxygen therapy (OR 2.52, 95% CI 1.40-4.52, p = 0.002) and ICU admission (OR 4.34, 95% CI 1.38-13.67, p = 0.012) after adjusting for confounders. In the late group there was a trend towards a higher risk of clinical worsening (OR 2.13, 95% CI 0.98-4.64, p = 0.056) and need for any oxygen therapy (OR 1.85, 95% CI 0.94-3.64, p = 0.074). CONCLUSION: Compared to patients who received remdesivir within the first 3 days after symptom onset, administering remdesivir after day 3 in hospitalized COVID-19 patients is associated with higher risk for complications, such as the need for high-flow oxygen therapy and ICU admission.

A retrospective analysis of clinical features of patients hospitalized with SARS-CoV-2 Omicron variants BA.1 and BA.2.

The causative agent of the ongoing Corona virus disease 2019 (COVID-19) pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has acquired a considerable amount of mutations, leading to changes in clinical manifestations and increased transmission. Recent studies based on animal disease models and data from the general population were reporting a higher pathogenicity of the BA.2 sublineage compared to BA.1. The aim of this study was to provide real world data on patients with the SARS-CoV-2 Omicron BA.1 and BA.2 subvariants treated at our center, highlighting similarities and differences in the clinical disease course. We retrospectively collected and analyzed the data of adult patients admitted with confirmed SARS-CoV-2 infection at the Department for Infectious Diseases and Tropical Medicine, Klinik Favoriten, Vienna, Austria. Patient characteristics including age, underlying diseases, vaccination status and outcome were compared between patients with the BA.1 and BA.2 subvariants. Between January 2022 and May 2022 we included 168 patients infected with Omicron BA.1 and 100 patients with BA.2. Patients admitted with BA.2 were significantly older, more often fully immunized and required less dexamethasone than patients with BA.1. No substantial differences were identified between patients infected with BA.1 and BA.2 regarding BMI, laboratory findings, need for supplemental oxygen, mortality and other evaluated comorbidities excepting active malignancies. The significantly larger percentage of fully immunized patients admitted with BA.2 is pointing to an increased transmissibility of this subvariant, while the comparable outcome of a somewhat older and sicker patient population might be indicative of reduced virulence.

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.

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.

SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients-A Single-Center Experience.

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on the use of tixagevimab/cilgavimab and sotrovimab as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PrEP in immunocompromised patients, comparing the evolution of antibody levels and reporting the incidence of breakthrough infections. A retrospective, single-center analysis was conducted including 132 immunocompromised patients with inadequate vaccine response, who received COVID-PrEP at our clinic between January and June 2022. Initially, 95 patients received sotrovimab while 37 patients received tixagevimab/cilgavimab. Antibody levels after first PrEP with sotrovimab remain high for several months after infusion (median 10,058 and 7235 BAU/mL after 1 and 3 months, respectively), with higher titers than after tixagevimab/cilgavimab injection even 3 months later (7235 vs. 1647 BAU/mL, p = 0.0007). Overall, breakthrough infections were rare (13/132, 10%) when compared to overall infection rates during this period (over 30% of the Austrian population), with mild disease course and rapid viral clearance (median 10 days). Sotrovimab may be an additional option for SARS-CoV-2 PrEP.

Early administration of remdesivir may reduce mortality in hospitalized COVID-19 patients : A propensity score matched analysis.

BACKGROUND: Remdesivir is the only antiviral agent approved for the treatment of hospitalized coronavirus disease 2019 (COVID-19) patients requiring supplemental oxygen. Studies show conflicting results regarding its effect on mortality. METHODS: In this single center observational study, we included adult hospitalized COVID-19 patients. Patients who were treated with remdesivir were compared to controls. Remdesivir was administered for 5 days. To adjust for any imbalances in our cohort, a propensity score matched analysis was performed. The aim of our study was to analyze the effect of remdesivir on in-hospital mortality and length of stay (LOS). RESULTS: After propensity score matching, 350 patients (175 remdesivir, 175 controls) were included in our analysis. Overall, in-hospital mortality was not significantly different between groups remdesivir 5.7% [10/175] vs. control 8.6% [15/175], hazard ratio 0.50, 95% confidence interval (CI) 0.22-1.12, p = 0.091. Subgroup analysis showed a significant reduction of in-hospital mortality in patients who were treated with remdesivir ≤ 7 days of symptom onset remdesivir 4.2% [5/121] vs. control 10.4% [13/125], hazard ratio 0.26, 95% CI 0.09 to 0.75, p = 0.012 and in female patients remdesivir 2.9% [2/69] vs. control 12.2% [9/74], hazard ratio 0.18 95%CI 0.04 to 0.85, p = 0.03. Patients in the remdesivir group had a significantly longer LOS (11 days vs. 9 days, p = 0.046). CONCLUSION: Remdesivir did not reduce in-hospital mortality in our whole propensity score matched cohort, but subgroup analysis showed a significant mortality reduction in female patients and in patients treated within ≤ 7 days of symptom onset. Remdesivir may reduce mortality in patients who are treated in the early stages of illness.

Whipple's disease diagnosed in a patient with suspected sarcoidosis.

This paper presents a case of a 51-year-old patient with chronic diarrhea, weight loss, polyarthralgia, and diffuse lymphadenopathy. Laboratory work-up showed anemia, leukocytosis and thrombocytosis, and increased C-reactive protein (CRP). Due to an inconspicuous differential leukocyte count and lymph node biopsy findings showing granulomatous lymphadenopathy, sarcoidosis was initially suspected. Colonoscopy found no abnormalities and duodenal biopsies showed negative Periodic acid-Schiff stains. However, PCR testing on these biopsies revealed Tropheryma whipplei DNA. Further PCR testing of urine and cerebrospinal fluid also revealed T. whipplei DNA. The patient was treated with ceftriaxone for 2 weeks followed by trimethoprim for a year. A rapid improvement of his symptoms was seen.