Complementarity determining regions in SARS-CoV-2 hybrid immunity.

Pre-vaccination SARS-CoV-2 infection can boost protection elicited by COVID-19 vaccination and post-vaccination breakthrough SARS-CoV-2 infection can boost existing immunity conferred by COVID-19 vaccination. Such 'hybrid immunity' is effective against SARS-CoV-2 variants. In order to understand 'hybrid immunity' at the molecular level we studied the complementarity determining regions (CDR) of anti-RBD (receptor binding domain) antibodies isolated from individuals with 'hybrid immunity' as well as from 'naive' (not SARS-CoV-2 infected) vaccinated individuals. CDR analysis was done by liquid chromatography/mass spectrometry-mass spectrometry. Principal component analysis and partial least square differential analysis showed that COVID-19 vaccinated people share CDR profiles and that pre-vaccination SARS-CoV-2 infection or breakthrough infection further shape the CDR profile, with a CDR profile in hybrid immunity that clustered away from the CDR profile in vaccinated people without infection. Thus, our results show a CDR profile in hybrid immunity that is distinct from the vaccination-induced CDR profile.

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium.

To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough infections (BTI) in healthcare workers (n = 84) upon BNT162b2 vaccination in a real-world setting. Firstly, serology was determined through immunoassays. Secondly, antibody functionality was analyzed via in vitro binding inhibition and pseudovirus neutralization and circulating receptor-binding domain (RBD)-specific B cells were assessed. Moreover, the induction of SARS-CoV-2-specific T cells was investigated by an interferon-γ release assay combined with flowcytometric profiling of activated CD4+ and CD8+ T cells. Within individuals that did not experience BTI (n = 62), vaccine-induced humoral and cellular immune responses were not correlated. Interestingly, waning over time was more pronounced within humoral compared to cellular immunity. In particular, 45 of these 62 subjects no longer displayed functional neutralization against the delta variant of concern (VoC) at long-term follow-up. Noteworthily, we reported a high incidence of symptomatic BTI cases (17.11%) caused by alpha and delta VoCs, although vaccine-induced immunity was only slightly reduced compared to subjects without BTI at mid-term follow-up.

Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model.

Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent patient with COVID-19, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 D614G, beta, gamma, and delta infection in vitro, with three mAbs neutralizing omicron as well. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta, and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 µg/mL, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.

An abrupt rise of coagulation error messages on ACL TOP automated analysers.

INTRODUCTION: Blood coagulation tests (BCT) are very important for clinicians to diagnose bleeding or thrombotic disorders and to monitor anticoagulant therapy. CASE DESCRIPTION: On a Saturday morning, a laboratory technician noted an abrupt rise in the number of coagulation error messages on our ALC TOP analysers. Visual inspection revealed the presence of partially and/or fully clotted citrate tubes and prompted the clinical biologist to further investigate a potential preanalytical cause. CONSIDERED CAUSES: Partially or fully clotted blood in citrate tubes can have multiple causes including improper mixing of the tube, under- or overfilling or combining blood samples from different tubes into one citrate tube. WHAT HAPPENED: The affected citrate tubes originated mostly from the same clinical departments. Moreover, all the affected tubes shared the same lot number (1 of 7 in use at the time). Visual inspection of 7 unopened boxes of 100 citrate tubes of this lot number revealed one box with nine completely empty and two partially filled tubes and one box with two partially filled tubes. No under-filled tubes were found in the other 5 boxes. DISCUSSION: The blood to additive ratio is crucial for BCT. A sudden rise in clot errors should trigger a thorough investigation to identify the cause. MAIN LESSON: Laboratories should regularly monitor and evaluate the percentage of clotted samples as a quality indicator at scheduled time points. A problem with the volume of additive in citrate tubes should be considered as a possible cause.

Letermovir for prophylaxis of cytomegalovirus manifestations in adult allogeneic hematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) manifestations remain important complications after allogeneic hematopoietic stem cell transplantation (HSCT), even in the current era. Unfortunately, available anti-CMV agents, mainly viral polymerase inhibitors, have a substantial risk of myelosuppression and nephrotoxicity. Letermovir, a novel anti-CMV drug that targets the viral terminase complex, has recently been approved for the prevention of clinically significant CMV infection in adult CMV seropositive hematopoietic stem cell transplantation recipients. This molecule could become a paradigm-shifting drug in preventing CMV manifestations based on its novel mechanism of action, lack of cross-resistance with available drugs, proven efficacy in a large randomized clinical trial, and its beneficial toxicity and tolerability profile. Drug-drug interactions and the lack of any activity against other viruses are the main shortcomings of letermovir.