SARS-CoV-2 Neutralization Capacity in Hemodialysis Patients with and without a Fifth Vaccination with the Updated Comirnaty Original/Omicron BA.4-5 Vaccine

Background: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. Methods: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. Results: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. Conclusion: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection

Improved SARS-CoV-2 Neutralization of Delta and Omicron BA.1 Variants of Concern after Fourth Vaccination in Hemodialysis Patients

Hemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date, it is unclear if hemodialysis patients benefit from four vaccinations. A total of 142 hemodialysis patients received four COVID-19 vaccinations until March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Delta (B.1.617.2), or Omicron (B.1.1.529, sub-lineage BA.1) to determine serum infection neutralization capacity. Four weeks after the fourth vaccination, serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3–1560.8) to 2560.0 (1174.0–2560.0) for the Delta VoC, and from 37.5 (20.0–198.8) to 668.5 (182.2–2560.0) for the Omicron VoC (each p p p = 0.051). Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron-variants. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

International audienceBackground: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)