No abstract

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.

Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.

are reported in Supplementary Table 2. Of all participants in the immunogenicity subcohort, 50.4% were ≥60 years old, 51.7% were considered at-risk for severe COVID-19 (defined as having one or more comorbidities associated with elevated risk of severe COVID-19 1 ) and 44.8% had been assigned female sex at birth. At US sites, 49.3% had minority status (defined as other than White Non-Hispanic). The immunogenicity subcohort was 26.0% from Latin America, 23.9% from South Africa and 50.0% from the United States. Supplementary Tables 3-5 provide demographics and clinical characteristics of the immunogenicity subcohort by geographic region.

Summary Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID‐19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin ( p = 0.52), platelet count ( p = 0.67), absolute lymphocyte ( p = 0.42) and neutrophil ( p = 0.98) counts prior to and after completion of vaccination series. Relapse after vaccination, defined as a progressive decline in counts requiring treatment, occurred in three patients (6%). Humoural response was detectable in 90% (28/31) of cases by reduction in an in‐vitro Angiotensin II Converting Enzyme (ACE2) binding and neutralization assay, even in patients receiving ciclosporin (10/11, 90.1%). Comparison of spike‐specific T‐cell responses in 27 SAA patients and 10 control subjects revealed qualitatively similar CD4 + Th1‐dominant responses to vaccination. There was no difference in CD4 + ( p = 0.77) or CD8 + ( p = 0.74) T‐cell responses between patients on or off ciclosporin therapy at the time of vaccination. Our data highlight appropriate humoural and cellular responses in SAA previously treated with IST and true relapse after vaccination is rare.

gender, age, and even facial expressions that is entirely separate from their original, unique persona. In some instances, an aura has been reported to supersede an alter being pulled from the unconscious to the subconscious. 7 The memories that many of the alters elicit are often entirely different from what the original persona has experienced, so much so that it cannot yet be explained by dementia or any other medical condition. 8 DID and other psychiatric disorders such as schizophrenia have some diagnostic features in common that can often make it challenging to differentiate these comparable conditions. Schizophrenia and DID may both exhibit auditory hallucinations, negative symptoms, some degree of cortical atrophy, and are both often associated with comorbid substance abuse. In current literature, however, clinicians have found some differentiating ideas and evidence that suggest a number of key differences between these disorders. Of note is the finding that the auditory hallucination manifested in up to 80% of patients with DID often manifest at an early age, are experienced as internal in origin, and rarely responds to antipsychotic medication. 8 Conversely, patients with schizophrenia experience hallucinations as environmental, third person, external, or internal in origin and this is usually associated with negative symptoms such as flat affect, catatonia, associability, and anhedonia. Schizophrenia has also shown better response profiles to antipsychotic medication compared to DID. 9 Some patients diagnosed with schizophrenia have also reported higher delusion scores than DID. It is important to note that one of the major diagnostic differences between these disorders is the presence of amnesia or significant disparities in time. Some theories have suggested that DID patients engage in an autohypnotic phenomenon, as a defense mechanism, and have endured significant childhood trauma that is hypothesized to potentiate the onset of the disorder. 8 In contrast, childhood trauma does not seem to be directly related to the onset of schizophrenia and other psychiatric conditions. There is evidence that up to 90% of patients with DID also meet the diagnostic criteria for PTSD. This comorbidity is important to note when examining brain imaging. In addition, other conditions such as borderline personality disorder, bipolar disorder, anxiety disorders, dysfunctional early childhood attachment styles, and childhood neglect have all been implicated or associated with DID in literature. 10 Risk factors for DID include but are not limited to chronic childhood trauma, young age (onset from 28-34 years old), suicidal ideation with previous attempts, monozygotic twins, promiscuity, gender dysphoria, substance abuse, comorbid psychiatric conditions, and depersonalization. 8,10 Many psychiatric disorders are associated with significant changes in brain morphology at gross and molecular levels. The aim of our study is to explore the possibility of using volumetric analysis of specific brain regions to support the diagno...