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.

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.

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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.