Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study.

BACKGROUND: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear. OBJECTIVE: To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID. DESIGN: Prospective observational cohort study. SETTING: Two U.S. CID referral centers. PARTICIPANTS: Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination. MEASUREMENTS: Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination. RESULTS: Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies. LIMITATIONS: Small sample that lacked demographic diversity, and residual confounding. CONCLUSION: Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study. PRIMARY FUNDING SOURCE: The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Gaps in cognitive care among older patients undergoing spine surgery.

INTRODUCTION: Among older adults undergoing surgery, postoperative delirium is the most common complication. Cognitive impairment and dementia are major risk factors for postoperative delirium, yet they are frequently under-recognized. It is well established that applying delirium preventive interventions to at-risk individuals can reduce the likelihood of delirium by up to 40%. The aim of this study was to evaluate how often delirium preventive interventions are missing in patients at risk for delirium due to baseline cognitive impairment. METHODS: We conducted a retrospective study using data from the observational study Perioperative Anesthesia Neurocognitive Disorder Assessment-Geriatric (PANDA-G) and clinical data from the University of California San Francisco delirium prevention bundle. Patients age 65+ received preoperative multidomain cognitive assessment as part of a research protocol prior to undergoing inpatient spine surgery at a single major academic institution. Results of the cognitive testing were not available to clinical teams. Using electronic medical records, we evaluated if patients who were cognitively impaired at baseline received delirium prevention orders, sleep orders, and avoidance of AGS Beers Criteria® potentially inappropriate medications. RESULTS: Of the 245 patients included in the study, 42% were women. The mean [SD] age was 72 [5.2] years. Preoperative cognitive impairment was identified in 40% of participants (N = 98), and of these, 34% had postoperative delirium. Of patients with preoperative cognitive impairment, 45% did not receive delirium preventive orders, 43% received PIMs, and 49% were missing sleep orders. At least one of the three delirium preventive interventions was missing in 70% of the patients. DISCUSSION: Undiagnosed preoperative cognitive impairment among older adults undergoing spine surgery is common. When cognitive test results were not available to clinicians, patients with baseline cognitive impairment frequently did not receive evidence-based delirium preventive interventions. These findings highlight an opportunity to improve perioperative brain health care via preoperative cognitive assessment and clinical communication.

Sleep Disturbance and SARS-CoV-2 Vaccinations in Patients With Chronic Inflammatory Disease.

OBJECTIVE: Immunocompromised patients with chronic inflammatory disease (CID) may have experienced additional psychosocial burden during the COVID-19 pandemic due to their immunocompromised status. This study was undertaken to determine if vaccination would result in improved patient-reported outcomes longitudinally among individuals with CID undergoing SARS-CoV-2 vaccination regardless of baseline anxiety. METHODS: Data are from a cohort of individuals with CID from 2 sites who underwent SARS-CoV-2 vaccination. Participants completed 3 study visits before and after 2 messenger RNA vaccine doses in the initial vaccination series when clinical data were collected. Patient-reported outcomes were measured using the Patient-Reported Outcomes Measurement Information System 29-item Health Profile and expressed as T scores, with 2 groups stratified by high and low baseline anxiety. Mixed-effects models were used to examine longitudinal changes, adjusting for age, sex, and study site. RESULTS: A total of 72% of the cohort was female with a mean ± SD age of 48.1 ± 15.5 years. Overall, sleep disturbance improved following both doses of SARS-CoV-2 vaccinations, and anxiety decreased after the second dose. Physical function scores worsened but did not meet the minimally important difference threshold. When stratifying by baseline anxiety, improvement in anxiety, fatigue, and social participation were greater in the high anxiety group. Physical function worsened slightly in both groups, and sleep disturbance improved significantly in the high anxiety group. CONCLUSION: Sleep disturbance decreased in a significant and meaningful way in patients with CID upon vaccination. In patients with higher baseline anxiety, social participation increased, and anxiety, fatigue, and sleep disturbance decreased. Overall, results suggest that SARS-CoV-2 vaccination may improve mental health and well-being, particularly among those with greater anxiety.

Reactogenicity of the Messenger RNA SARS-CoV-2 Vaccines Associated With Immunogenicity in Patients With Autoimmune and Inflammatory Disease.

OBJECTIVE: Little is known regarding the reactogenicity and related SARS-CoV-2 vaccine response in patients with chronic inflammatory disease (CID). Our objective was to characterize the adverse event profile of CID patients following SARS-CoV-2 vaccination and understand the relationship between reactogenicity and immunogenicity of SARS-CoV-2 vaccines. METHODS: CID patients and healthy controls eligible to receive messenger RNA (mRNA) SARS-CoV-2 vaccines participated in 3 study visits (pre-vaccine, after dose 1, and after dose 2) in which blood and clinical data were collected. Assessment of adverse events were solicited within 7 days of receiving each dose. Serum anti-SARS-CoV-2 spike IgG ± antibody titers were quantified following vaccination. Statistical analysis was performed utilizing mixed models and tobit regressions, with adjustment for covariates. RESULTS: The present study included 441 participants (322 CID patients and 119 control subjects). Compared to controls, CID patients reported greater symptom severity after dose 1 (P = 0.0001), including more myalgia and fatigue (P < 0.05). For immunogenicity, a higher symptom severity after dose 1 and a higher number of symptoms after dose 2 was associated with higher antibody titers (P ≤ 0.05). Each increase of 1 symptom was associated with a 15.1% increase in antibody titer. Symptom association was strongest with site pain after dose 1 (105%; P = 0.03) and fatigue after dose 2 (113%; P = 0.004). CONCLUSION: Patients with CID have a distinct reactogenicity profile following SARS-CoV-2 vaccination compared to controls. Furthermore, there is an association between increased reactogenicity and increased vaccine response. This finding may speak to the more variable immunogenicity in CID patients and may be an important indicator of vaccine response to the novel SARS-CoV-2 vaccines.

Burst Suppression During General Anesthesia and Postoperative Outcomes: Mini Review.

In the last decade, burst suppression has been increasingly studied by many to examine whether it is a mechanism leading to postoperative cognitive impairment. Despite a lack of consensus across trials, the current state of research suggests that electroencephalogram (EEG) burst suppression, duration and EEG emergence trajectory may predict postoperative delirium (POD). A mini literature review regarding evidence about burst suppression impact and susceptibilities was conducted, resulting in conflicting studies. Primarily, studies have used different algorithm values to replace visual burst suppression examination, although many studies have since emerged showing that algorithms underestimate burst suppression duration. As these methods may not be interchangeable with visual analysis of raw data, it is a potential factor for the current heterogeneity between data. Even though additional research trials incorporating the use of raw EEG data are necessary, the data currently show that monitoring with commercial intraoperative EEG machines that use EEG indices to estimate burst suppression may help physicians identify burst suppression and guide anesthetic titration during surgery. These modifications in anesthetics could lead to preventing unfavorable outcomes. Furthermore, some studies suggest that brain age, baseline impairment, and certain medications are risk factors for burst suppression and postoperative delirium. These patient characteristics, in conjunction with intraoperative EEG monitoring, could be used for individualized patient care. Future studies on the feasibility of raw EEG monitoring, new technologies for anesthetic monitoring and titration, and patient-associated risk factors are crucial to our continued understanding of burst suppression and postoperative delirium.