Immunogenicity and clinical effectiveness of mRNA vaccine booster against SARS-CoV-2 Omicron in patients with haematological malignancies: A national prospective cohort study.

Information regarding the protective anti-SARS-CoV-2 antibody levels and the effectiveness of the mRNA vaccines against the Omicron variant in patients with haematological malignancies is limited. We prospectively followed two times BNT162b2 vaccinated oncohaematological patients (n = 1010) without prior COVID-19 for PCR-confirmed breakthrough infections during the Alpha/Delta and the Omicron phases of the pandemic. Anti-S1-IgG levels were longitudinally monitored in patients who had received the third (booster) vaccine dose. Patients with anti-S1-IgG levels <50 BAU/mL 1 month after the booster had a higher risk of Omicron infections (RR 1.91; 95% CI 1.39-2.63; p = 0.0001) and severe infections (RR 8.74; 95% CI 3.99-19.1; p < 0.0001). Conversely, the risk of severe COVID-19 was <1% with anti-S1-IgG levels >500 BAU/mL and neutralizing antibody concentrations >50 U/mL. The risks of breakthrough Omicron infections (HR 0.55; 95% CI 0.32-0.96; p = 0.034) and severe COVID-19 (HR 0.27; 95% 0.11-0.7; p = 0.0074) were lower among patients who had received the booster dose. In conclusion, low antibody levels are associated with significantly increased risk of both the breakthrough Omicron infections and severe COVID-19. The third mRNA vaccine dose improved the protection against the Omicron and reduced the risk of severe disease.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. METHODS: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. DISCUSSION: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

In-hospital mortality during the wild-type, alpha, delta, and omicron SARS-CoV-2 waves: a multinational cohort study in the EuCARE project.

Background: Investigating outcomes of hospitalised COVID-19 patients throughout the pandemic is crucial to understand the impact of different SARS-CoV-2 variants. We compared 28-day in-hospital mortality of Wild-type, Alpha, Delta, and Omicron variant infections. Whether the difference in risk by variant varied by age was also evaluated. Methods: We conducted a cohort study including patients ≥18 years, hospitalised between 2020 and 02-01 and 2022-10-15 with a SARS-CoV-2 positive test, from nine countries. Variant was classified based on sequenced viruses or from national public metadata. Mortality was compared using the cumulative incidence function and subdistribution hazard ratios (SHR) adjusted for age, sex, calendar time, and comorbidities. Results were shown age-stratified due to effect measure modification (P < 0.0001 for interaction between age and variant). Findings: We included 38,585 participants: 19,763 Wild-type, 6387 Alpha, 3640 Delta, and 8795 Omicron. The cumulative incidence of mortality decreased throughout the study period. Among participants ≥70 years, the adjusted SHR (95% confidence interval) for Delta vs. Omicron was 1.66 (1.29-2.13). This estimate was 1.66 (1.17-2.36) for Alpha vs. Omicron, and 1.34 (0.92-1.95) for Wild-type vs. Omicron. These were 1.21 (0.81-1.82), 1.21 (0.68-2.17), and 0.98 (0.53-1.82) among unvaccinated participants. When comparing Omicron sublineages, the aSHR for BA.1 was 1.92 (1.43-2.58) compared to BA.2 and 1.52 (1.11-2.08) compared to BA.5. Interpretation: The herein observed decrease in in-hospital mortality seems to reflect a combined effect of immunity from vaccinations and previous infections, although differences in virulence between SARS-CoV-2 variants may also have contributed. Funding: European Union's Horizon Europe Research and Innovation Programme.

The COVID-19 pandemic reveals the wide-ranging role of biobanks.

The pandemic of COVID-19 reached an unprecedented scale in terms of spread and deaths, its mitigation required a joint effort of governments, hospitals, private companies and other organizations. One type of organization that could undertake a major role in the process is biobank - a mediator between clinical practice and research. Naturally, biobanks are well equipped to alleviate the burden of a pandemic with their expertise in biospecimen and health information collection, sample preparation and storage, bioethics and project management. Here, we present the participation of Vilnius Santaros Klinikos Biobank (BB VSK), Lithuania in the overall management of the pandemics on the national level. We further discuss the role of biobanks in preparation and management of future pandemics.

Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study.

BACKGROUND: Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. METHODS: Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0-10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov, NCT04871165. FINDINGS: Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18-60 years and 67 healthy health-care workers in the same age group. Patients aged 18-60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292-20 672] vs 21 395 AU/mL [14 831-33 553]; p<0·0001). Compared with untreated patients with haematological malignancies (n=53; median 5761 AU/mL [629-16 141]), patients actively treated with Bruton tyrosine kinase inhibitors (BTKIs; n=44; 0 AU/mL [0-7]; p<0·0001), ruxolitinib (n=16; 10 AU/mL [0-45]; p<0·0001), venetoclax (n=10; 4 AU/mL [0-1218]; p=0·0005), or anti-CD20 antibody therapy (n=87; 17 AU/mL [1-2319]; p<0·0001) showed particularly poor anti-S1 IgG antibody responses following two BNT162b2 doses. Patients being treated with tyrosine kinase inhibitors (n=41; 10 537 AU/mL [IQR 2335-19 388]) or patients who received autologous haematopoietic stem-cell transplantation (HSCT; n=192; 6203 AU/mL [1451-16 834]) or allogeneic HSCT (n=122; 6304 AU/mL [1120-16 913]) were among the subgroups with the highest numerical responses. Nine SARS-CoV-2 infections and three COVID-19 deaths were observed among fully vaccinated patients with haematological malignancies. INTERPRETATION: Patients with haematological malignancies mount blunted and heterogeneous antibody responses to the full course of BNT162b2 mRNA vaccination. Patients who are actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and might be left unprotected from SARS-CoV-2 infection. Breakthrough severe SARS-CoV-2 infections in fully vaccinated patients with haematological malignancies emphasise the importance of ongoing strict adherence to non-pharmacological interventions and household vaccination while SARS-CoV-2 is circulating in the community. FUNDING: Vilnius University Hospital Santaros Klinikos. TRANSLATION: For the Lithuanian translation of the abstract see Supplementary Materials section.