Application of machine learning algorithms to identify serological predictors of COVID-19 severity and outcomes.

Background: Critically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized.

Methods: In a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and more than 20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms.

A Third COVID-19 Vaccine Dose in Kidney Transplant Recipients Induces Antibody Response to Vaccine and Omicron Variants but Shows Limited Ig Subclass Switching.

Unlabelled: Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as to Omicron variants BA.

The contributions of T cell-mediated immunity to protection from vaccine-preventable diseases: A primer.

In the face of the ever-present burden of emerging and reemerging infectious diseases, there is a growing need to comprehensively assess individual- and population-level immunity to vaccine-preventable diseases (VPDs). Many of these efforts, however, focus exclusively on antibody-mediated immunity, ignoring the role of T cells. Aimed at clinicians, public health practioners, and others who play central roles in human vaccine research but do not have formal training in immunology, we review how vaccines against infectious diseases elicit T cell responses, what types of vaccines elicit T cell responses, and how T cell responses are measured.

Sex and gender differences in adverse events following influenza and COVID-19 vaccination.

Introduction: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized.

Methods: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

Sex and gender differences in adverse events following receipt of influenza and COVID-19 vaccination among healthcare workers.

Introduction: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. We sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized.

Methods: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns.

Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies.

Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC).

Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes.

Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and >20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms.

Effects of Biological Sex and Pregnancy on SARS-CoV-2 Pathogenesis and Vaccine Outcomes.

SARS-CoV-2 is the causative agent of COVID-19 in humans and has resulted in the death of millions of people worldwide. Similar numbers of infections have been documented in males and females; males, however, are more likely than females to be hospitalized, require intensive care unit, or die from COVID-19. The mechanisms that account for this are multi-factorial and are likely to include differential expression of ACE2 and TMPRSS2 molecules that are required for viral entry into hosts cells and sex differences in the immune response, which are due to modulation of cellular functions by sex hormones and differences in chromosomal gene expression.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

Background: Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination.

Development and characterization of a plant-derived norovirus-like particle vaccine.

Background: Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains.

Spike-protein proteolytic antibodies in COVID-19 convalescent plasma contribute to SARS-CoV-2 neutralization.

Understanding the mechanisms of antibody-mediated neutralization of SARS-CoV-2 is critical in combating the COVID-19 pandemic. Based on previous reports of antibody catalysis, we investigated the proteolysis of spike (S) by antibodies in COVID-19 convalescent plasma (CCP) and its contribution to viral neutralization. Quenched fluorescent peptides were designed based on S epitopes to sensitively detect antibody-mediated proteolysis.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Background: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.

Methods: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination.

The intersection of gender and race in older adults' decision to receive COVID-19 vaccines.

COVID-19 vaccines are essential public health tools for protecting older adults, who are at high risk of severe outcomes associated with COVID-19. Little is known, however, about how older adults approach the decision to receive a COVID-19 vaccine. We hypothesized that intersections between gender and race may provide unique insight into the decision-making process and the factors that lead to vaccine uptake among hesitant individuals.

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults.

Sex differences in the immune system are dynamic throughout the lifespan and contribute to heterogeneity in the risk of infectious diseases and the response to vaccination in older adults. The importance of the intersection between sex and age in immunity to viral respiratory diseases is clearly demonstrated by the increased prevalence and severity of influenza and COVID-19 in older males compared to older females. Despite sex and age biases in the epidemiology and clinical manifestations of disease, these host factors are often ignored in vaccine research.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

Background: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized.

Methods: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs).

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

Background: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma.

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma.

Sex-specific effects of aging on humoral immune responses to repeated influenza vaccination in older adults.

Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction.

Beyond a Zero-Sum Game: How Does the Impact of COVID-19 Vary by Gender?

Epidemics and pandemics, like COVID-19, are not gender neutral. Much of the current work on gender, sex, and COVID-19, however, has seemed implicitly or explicitly to be attempting to demonstrate that either men or women have been hardest hit, treating differences between women and men as though it is not important to understand how each group is affected by the virus. This approach often leaves out the effect on gender and sexual minorities entirely.

Differences and disparities in seasonal influenza vaccine, acceptance, adverse reactions, and coverage by age, sex, gender, and race.

Background: Influenza is a significant threat to public health worldwide. Despite the widespread availability of effective and generally safe vaccines, the acceptance and coverage of influenza vaccines are significantly lower than recommended. Sociodemographic variables are known to be potential predictors of differential influenza vaccine uptake and outcomes.