Short-course Early Outpatient Remdesivir Prevents Severe Disease due to COVID-19 in Organ Transplant Recipients During the Omicron BA.2 Wave.

Solid organ transplant recipients (SOTr) remain at risk of severe COVID-19. Several previous early therapies are no longer effective against new circulating variants. We performed a prospective cohort study in outpatient adult SOTr during the Omicron BA.2 wave (April-May 2022), to determine the effectiveness of 3 doses of remdesivir given within 7 days of symptoms onset. Patients were followed for at least 30 days. The primary outcome was hospitalization. Of 210 SOTr that had COVID-19, we included 192. The median age was 54.5 years and 61.5% were men. The most common transplants were kidney (41.7%), lung (19.3%), liver (18.8%), and heart (6.3%). Most patients (90.1%) had previously received ≥3 COVID-19 vaccine doses. Fifteen(7.8%) were hospitalized, 5(2.6%) required supplemental oxygen, 3(1.6%) ICU admission, and 2(1%) mechanical ventilation with 2(1%) deaths. Age and multiple comorbidities were risk factors for hospitalization. Early remdesivir significantly decreased the hospitalization rate: adjusted hazard ratio 0.12 (95%CI: 0.03 to 0.057). The adjusted number needed to treat to prevent one hospitalization was 15.2 (95%CI: 13.6 to 31.4). No patient that received early remdesivir needed ICU admission or died. In a cohort of SOTr with COVID-19 infection, administration of 3-dose early remdesivir independently reduced the disease severity.

Homotypic and heterotypic immune responses to Omicron variant in immunocompromised patients in diverse clinical settings.

Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4+ and CD8+ T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection.

Impact of Vaccination and Early Monoclonal Antibody Therapy on COVID-19 Outcomes in Organ Transplant Recipients During the Omicron Wave.

BACKGROUND: Solid organ transplant (SOT) recipients are at high risk for complications from COVID-19 and vaccine breakthrough infections are common. We determined the effectiveness of ≥3 doses of mRNA vaccine and early monoclonal antibody therapy in reducing disease severity against the Omicron (B.1.1.529) variant. METHODS: Prospective cohort study of consecutive SOT recipients with SARS-CoV-2 infection referred to our transplant center who were followed for at least 30 days. The primary outcome was supplemental oxygen requirement. Effectiveness of sotrovimab and ≥3 vaccine doses was estimated using adjusted risk ratios (RR). RESULTS: Three-hundred adult organ transplant recipients were included. Seventy-one patients (24.1%) were hospitalized, 44(14.9%) required supplemental oxygen, 19(6.5%) were admitted to the ICU, 15(5.1%) required MV, and 13(4.4%) died. On multivariate analysis, age and multiple comorbidities were risk factors for oxygen requirement. Both receipt of ≥3 vaccine doses prior to SARS-CoV-2 infection and receipt of sotrovimab in the first 7 days of symptom onset was associated with a reduction in the need for supplemental oxygen [RR 0.30 (95%CI:0.17 to 0.54) and RR 0.24 (95% CI:0.1 to 0.59) respectively]. For sotrovimab, the number needed to treat (NNT) to prevent one patient requiring oxygen was 6.64 (95%CI:4.56-13.66). Both sotrovimab use and having received ≥3 vaccine doses were also associated with a shorter hospitalization length of stay. CONCLUSION: In a cohort of SOT recipients with Omicron variant COVID-19 infection, prior receipt of ≥3 mRNA vaccine doses and early monoclonal antibody therapy were independently associated with significantly reduced disease severity.