Formal and informal venous thromboembolism risk assessment and impact on prescribing of thromboprophylaxis: a retrospective cohort study.

BACKGROUND: Hospital-acquired thrombosis (HAT) is a leading cause of preventable death and disability worldwide. HAT includes any venous thromboembolic (VTE) event occurring in-hospital or within 90-days of hospitalisation. Despite availability of evidence-based guidelines for HAT risk assessment and prophylaxis, guidelines are still underutilised. AIM: To determine the proportion of patients who developed HAT that could have been potentially prevented with appropriate VTE risk assessment and prophylaxis at a large public hospital in New Zealand. Additionally, the predictors of VTE risk assessment and thromboprophylaxis were examined. METHOD: VTE patients admitted under general medicine, reablement, general surgery, or orthopaedic surgery service were identified using ICD-10-AM codes. Data were collected on patient characteristics, VTE risk factors, and the thromboprophylaxis regimen prescribed. The hospital VTE guidelines were used to determine rates of VTE risk assessment and the appropriateness of thromboprophylaxis. RESULTS: Of 1302 VTE patients, 213 HATs were identified. Of these, 116 (54%) received VTE risk assessment, and 98 (46%) received thromboprophylaxis. Patients who received VTE risk assessment were 15 times more likely to receive thromboprophylaxis (odds ratio [OR] = 15.4; 95% CI 7.65-30.98) and 2.8 times more likely to receive appropriate thromboprophylaxis (OR = 2.79; 95% CI 1.59-4.89). CONCLUSION: A large proportion of high-risk patients who were admitted to medical, general surgery and reablement services and who developed HAT did not receive VTE risk assessment and thromboprophylaxis during their index admission, demonstrating a significant gap between guideline recommendations and clinical practice. Implementing mandatory VTE risk assessment and adherence to guidelines to improve thromboprophylaxis prescription in hospitalised patients may help reduce the burden of HAT.

Anamnestic humoral correlates of immunity across SARS-CoV-2 variants of concern.

While immune correlates against SARS-CoV-2 are typically defined at peak immunogenicity following vaccination, immunologic responses that expand selectively during the anamnestic response following infection can provide mechanistic and detailed insights into the immune mechanisms of protection. Moreover, whether anamnestic correlates are conserved across variants of concern (VOC), including the Delta and more distant Omicron VOC, remains unclear. To define the anamnestic correlates of immunity, across VOCs, we deeply profiled the humoral immune response in individuals infected with sequence-confirmed Delta or Omicron VOC after completing the vaccination series. While limited acute N-terminal domain and receptor-binding domain (RBD)-specific immune expansion was observed following breakthrough infection, a significant immunodominant expansion of opsonophagocytic Spike-specific antibody responses focused largely on the conserved S2-domain of SARS-CoV-2 was observed. This S2-specific functional humoral response continued to evolve over 2-3 weeks following Delta or Omicron breakthrough, targeting multiple VOCs and common coronaviruses. Strong responses were observed on the fusion peptide (FP) region and the heptad repeat 1 (HR1) region adjacent to the RBD. Notably, the FP is highly conserved across SARS-related coronaviruses and even non-SARS-related betacoronavirus. Taken together, our results point to a critical role of highly conserved, functional S2-specific responses in the anamnestic antibody response to SARS-CoV-2 infection across VOCs. These humoral responses linked to virus clearance can guide next-generation vaccine-boosting approaches to confer broad protection against future SARS-related coronaviruses. IMPORTANCE The Spike protein of SARS-CoV-2 is the primary target of antibody-based recognition. Selective pressures, be it the adaption to human-to-human transmission or evasion of previously acquired immunity, have spurred the emergence of variants of the virus such as the Delta and Omicron lineages. Therefore, understanding how antibody responses are expanded in breakthrough cases of previously vaccinated individuals can provide insights into key correlates of protection against current and future variants. Here, we show that vaccinated individuals who had documented COVID-19 breakthrough showed anamnestic antibody expansions targeting the conserved S2 subdomain of Spike, particularly within the fusion peptide region. These S2-directed antibodies were highly leveraged for non-neutralizing, phagocytic functions and were similarly expanded independent of the variant. We propose that through deep profiling of anamnestic antibody responses in breakthrough cases, we can identify antigen targets susceptible to novel monoclonal antibody therapy or vaccination-boosting strategies.