Postvaccination Symptoms After a Third Dose of mRNA SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease: Results From CORALE-IBD.

BACKGROUND: The safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown. METHODS: We compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD. RESULTS: The study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse. CONCLUSION: The frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.

The postvaccination symptom profile in patients with IBD is unknown after a third mRNA COVID vaccine dose. In a cohort of 594 subjects with IBD, we demonstrated that 41% experienced any symptoms after a third dose, the vast majority of which were mild and lasted less than 2 days. Symptoms after third dose were less frequently reported than after the second dose.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds which were five times higher, our results suggest that further studies, are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.

Racial Disparities in Mortality Associated With Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis.

This study assessed the COVID-19 pandemic's impact on racial disparities in acute myocardial infarction (AMI) management and outcomes. We reviewed AMI patient management and outcomes in the pandemic's initial nine months, comparing COVID-19 and non-COVID-19 cases using 2020's National Inpatient Sample data. Our findings revealed that patients with concurrent AMI and COVID-19 had higher in-hospital mortality (aOR 3.19, 95% CI 2.63-3.88), increased mechanical ventilation (aOR 1.90, 95% CI 1.54-2.33), and higher initiation of hemodialysis (aOR 1.38, 95% CI 1.05-1.89) compared to those without COVID-19. Moreover, Black and Asian/Pacific Islander patients had higher in-hospital mortality than White patients, (aOR 2.13, 95% CI 1.35-3.59; aOR 3.41, 95% CI 1.5-8.37). Also, Black, Hispanic, and Asian/Pacific Islander patients showed higher odds of initiating hemodialysis (aOR 5.48, 95% CI 2.13-14.1; aOR 2.99, 95% CI 1.13-7.97; aOR 7.84, 95% CI 1.55-39.5), and were less likely to receive PCI for AMI (aOR 0.71, 95% CI 0.67-0.74; aOR 0.81, 95% CI 0.77-0.86; aOR 0.82, 95% CI 0.75-0.90). Black patients also showed less likelihood of undergoing CABG (aOR 0.55, 95% CI 0.49-0.61). Our study highlights elevated mortality and complications in COVID-19 AMI patients, emphasizing significant racial disparities. These findings underscore the pressing need for initiatives addressing healthcare disparities, enhancing access, and promoting culturally sensitive care to boost health equity.

BIRCH: An Automated Workflow for Evaluation, Correction, and Visualization of Batch Effect in Bottom-Up Mass Spectrometry-Based Proteomics Data.

Recent surges in large-scale mass spectrometry (MS)-based proteomics studies demand a concurrent rise in methods to facilitate reliable and reproducible data analysis. Quantification of proteins in MS analysis can be affected by variations in technical factors such as sample preparation and data acquisition conditions leading to batch effects, which adds to noise in the data set. This may in turn affect the effectiveness of any biological conclusions derived from the data. Here we present Batch-effect Identification, Representation, and Correction of Heterogeneous data (BIRCH), a workflow for analysis and correction of batch effect through an automated, versatile, and easy to use web-based tool with the goal of eliminating technical variation. BIRCH also supports diagnosis of the data to check for the presence of batch effects, feasibility of batch correction, and imputation to deal with missing values in the data set. To illustrate the relevance of the tool, we explore two case studies, including an iPSC-derived cell study and a Covid vaccine study to show different context-specific use cases. Ultimately this tool can be used as an extremely powerful approach for eliminating technical bias while retaining biological bias, toward understanding disease mechanisms and potential therapeutics.

Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Review of Immunologic Manifestations of COVID-19 Infection and Vaccination.

We herein summarize currently available and clinically relevant information regarding the human immune responses to SARS-CoV-2 infection and vaccination, in relation to COVID-19 outcomes with a focus on acute respiratory distress syndrome (ARDS) and myocarditis.

Outcomes of Extremely Prolonged (> 50 d) Venovenous Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure. DESIGN: Retrospective cohort study. SETTING: A large tertiary urban care center. PATIENTS: Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35-51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70-128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2-14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation. CONCLUSIONS: Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure.

Mechanically Ventilated Patients With Coronavirus Disease 2019 Had a Higher Chance of In-Hospital Death If Treated With High-Flow Nasal Cannula Oxygen Before Intubation.

BACKGROUND: The impact of high-flow nasal cannula (HFNC) on outcomes of patients with respiratory failure from coronavirus disease 2019 (COVID-19) is unknown. We sought to assess whether exposure to HFNC before intubation was associated with successful extubation and in-hospital mortality compared to patients receiving intubation only. METHODS: This single-center retrospective study examined patients with COVID-19-related respiratory failure from March 2020 to March 2021 who required HFNC, intubation, or both. Data were abstracted from the electronic health record. Use and duration of HFNC and intubation were examined' as well as demographics and clinical characteristics. We assessed the association between HFNC before intubation (versus without) and chance of successful extubation and in-hospital death using Cox proportional hazards models adjusting for age, sex, race/ethnicity, obesity, hypertension, diabetes, prior chronic obstructive pulmonary disease or asthma, HCO 3 , CO 2 , oxygen-saturation-to-inspired-oxygen (S:F) ratio, pulse, respiratory rate, temperature, and length of stay before intervention. RESULTS: A total of n = 440 patients were identified, of whom 311 (70.7%) received HFNC before intubation, and 129 (29.3%) were intubated without prior use of HFNC. Patients who received HFNC before intubation had a higher chance of in-hospital death (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.06-4.05). No difference was found in the chance of successful extubation between the 2 groups (0.70, 0.41-1.20). CONCLUSIONS: Among patients with respiratory failure from COVID-19 requiring mechanical ventilation, patients receiving HFNC before intubation had a higher chance of in-hospital death. Decisions on initial respiratory support modality should weigh the risks of intubation with potential increased mortality associated with HFNC.

Association of COVID-19 Vaccination With Risk for Incident Diabetes After COVID-19 Infection.

This cohort study compares the risk of new-onset hypertension, hyperlipidemia, and diabetes before and after COVID-19 infection among patients who were vaccinated vs unvaccinated before infection.

Excess risk for acute myocardial infarction mortality during the COVID-19 pandemic.

The COVID-19 pandemic has had a detrimental impact on the healthcare system. Our study armed to assess the extent and the disparity in excess acute myocardial infarction (AMI)-associated mortality during the pandemic, through the recent Omicron outbreak. Using data from the CDC's National Vital Statistics System, we identified 1 522 669 AMI-associated deaths occurring between 4/1/2012 and 3/31/2022. Accounting for seasonality, we compared age-standardized mortality rate (ASMR) for AMI-associated deaths between prepandemic and pandemic periods, including observed versus predicted ASMR, and examined temporal trends by demographic groups and region. Before the pandemic, AMI-associated mortality rates decreased across all subgroups. These trends reversed during the pandemic, with significant rises seen for the youngest-aged females and males even through the most recent period of the Omicron surge (10/2021-3/2022). The SAPC in the youngest and middle-age group in AMI-associated mortality increased by 5.3% (95% confidence interval [CI]: 1.6%-9.1%) and 3.4% (95% CI: 0.1%-6.8%), respectively. The excess death, defined as the difference between the observed and the predicted mortality rates, was most pronounced for the youngest (25-44 years) aged decedents, ranging from 23% to 34% for the youngest compared to 13%-18% for the oldest age groups. The trend of mortality suggests that age and sex disparities have persisted even through the recent Omicron surge, with excess AMI-associated mortality being most pronounced in younger-aged adults.

Influence of the COVID-19 Pandemic on Author Gender and Manuscript Acceptance Rates among Pulmonary and Critical Care Journals.

RATIONALE: The COVID-19 pandemic has negatively affected women more than men and may influence the publication of non-COVID research. OBJECTIVES: Evaluate whether the COVID-19 pandemic is associated with changes in manuscript acceptance rates among pulmonary/critical care journals, and gender-based disparities in these rates. METHODS: We analyzed first, senior, and corresponding-author gender (female vs. male, identified by matching first names in a validated Genderize database) of manuscripts submitted to four pulmonary/critical care journals between 1/1/18-12/31/20. We constructed interrupted time series regression models to evaluate whether the proportion of female first and senior authors of non-COVID-19 original research manuscripts changed with the pandemic. Next, we performed multivariable logistic regressions to evaluate the association of author gender with acceptance of original research manuscripts. RESULTS: Among 8,332 original research submissions, women comprised 39.9% and 28.3% of first and senior authors, respectively. We found no change in the proportion of female first or senior-authors of non-COVID-19 or COVID-19-submitted research manuscripts during the COVID-era. Non-COVID-19 manuscripts submitted during the COVID-era had reduced odds of acceptance, regardless of author gender (first-author: adjustedOR [aOR]0.46 [95%CI0.36-0.59]; senior-author: aOR0.46 [95%CI0.37-0.57]). Female senior-authorship was associated with decreased acceptance of non-COVID research manuscripts (crude rates: 14.4% [male] vs 13.2% [female]; aOR0.84, 95%CI0.71-0.99). CONCLUSIONS: Although female author submissions were not disproportionately influenced by COVID-19, we found evidence suggesting gender disparities in manuscript acceptance rates. Journals may need to consider strategies to reduce this disparity and academic institutions may need to factor our findings, including lower acceptance rates for non-COVID manuscripts, into promotion decisions.

Evidence of premature lymphocyte aging in people with low anti-spike antibody levels after BNT162b2 vaccination.

SARS-CoV-2 vaccines have unquestionably blunted the overall impact of the COVID-19 pandemic, but host factors such as age, sex, obesity, and other co-morbidities can affect vaccine efficacy. We identified individuals in a relatively healthy population of healthcare workers (CORALE study cohort) who had unexpectedly low peak anti-spike receptor binding domain (S-RBD) antibody levels after receiving the BNT162b2 vaccine. Compared to matched controls, "low responders" had fewer spike-specific antibody-producing B cells after the second and third/booster doses. Moreover, their spike-specific T cell receptor (TCR) repertoire had less depth and their CD4+ and CD8+T cell responses to spike peptide stimulation were less robust. Single cell transcriptomic evaluation of peripheral blood mononuclear cells revealed activation of aging pathways in low responder B and CD4+T cells that could underlie their attenuated anti-S-RBD antibody production. Premature lymphocyte aging may therefore contribute to a less effective humoral response and could reduce vaccination efficacy.

Awareness of SARS-CoV-2 Omicron Variant Infection Among Adults With Recent COVID-19 Seropositivity.

Importance: Some individuals who were infected by the SARS-CoV-2 Omicron variant may have been completely unaware of their infectious status while the virus was actively transmissible. Objective: To examine awareness of infectious status among individuals during the recent Omicron variant surge in a diverse and populous urban region of Los Angeles County. Design, Setting, and Participants: This cohort study analyzed the records of adult employees and patients of an academic medical center who were enrolled in a longitudinal COVID-19 serological study in Los Angeles County, California. These participants had 2 or more serial anti-nucleocapsid IgG (IgG-N) antibody measurements at least 1 month apart, with the first occurring after the end of a regional Delta variant surge (September 15, 2021) and a subsequent one occurring after the start of a regional Omicron variant surge (December 15, 2021). Adults with evidence of new SARS-CoV-2 infection occurring during the Omicron variant surge period through May 4, 2022, were included in the present study sample. Exposures: Recent Omicron variant infection as evidenced by SARS-CoV-2 seroconversion. Main Outcomes and Measures: Awareness of recent SARS-CoV-2 infection was ascertained from review of self-reported health updates, medical records, and COVID-19 testing data. Results: Of the 210 participants (median [range] age, 51 (23-84) years; 136 women [65%]) with serological evidence of recent Omicron variant infection, 44% (92) demonstrated awareness of any recent Omicron variant infection and 56% (118) reported being unaware of their infectious status. Among those who were unaware, 10% (12 of 118) reported having had any symptoms, which they attributed to a common cold or other non-SARS-CoV-2 infection. In multivariable analyses that accounted for demographic and clinical characteristics, participants who were health care employees of the medical center were more likely than nonemployees to be aware of their recent Omicron variant infection (adjusted odds ratio, 2.46; 95% CI, 1.30-4.65). Conclusions and Relevance: Results of this study suggest that more than half of adults with recent Omicron variant infection were unaware of their infectious status and that awareness was higher among health care employees than nonemployees, yet still low overall. Unawareness may be a highly prevalent factor associated with rapid person-to-person transmission within communities.