Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.

Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (n = 479) and immunocompromised individuals (n = 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or "Long-COVID"). Among immunocompromised individuals, 59% (n = 68) had an underlying hematologic malignancy; of those, 46% (n = 31) of individuals received cancer treatment <30 days prior to study blood collection. Ninety-eight percentage (n = 469) of immunocompetent and 81% (n = 93) of immunocompromised individuals had elevated RBD antibody titers (>1,000 U/mL), and of these, 60% (n = 281) and 44% (n = 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (n = 12) cohorts (P < 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes. IMPORTANCE: The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Capturing the Range of Disease Involvement in Localized Scleroderma: The Localized Scleroderma Total Severity Scale.

OBJECTIVE: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. METHODS: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. RESULTS: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. CONCLUSION: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies.

Characteristics and Presentations of Hospitalized Children Due to 3 Predominate COVID-19 Variants Within a Health Care Network.

Objective of this article is to describe differences in the demographic and clinical characteristics, severity of illness, and outcomes in pediatric patients with different SARS-CoV-2 variants. We conducted a retrospective study of pediatric patients admitted with COVID-19 during the 3 large waves of infection within a health network in New Jersey. We included demographic characteristics, clinical features, and outcomes and compared the data with respect to the different variants. Of 351 total patients included in this study, 74 were admitted during wave 1, 94 during wave 2, and 181 during wave 3. The median age of patients decreased from wave 1 (11.5 years) to wave 3 (3 years) (P = .0034). 87.7% of the patients were unvaccinated. The overall incidence of admissions due to pneumonia related to COVID-19 decreased in wave 3. COVID-19 bronchiolitis or croup admissions occurred mostly in wave 3. There was no significant difference in the number of patients requiring intensive care in any particular wave. Length of stay decreased across the waves (P < .0001). Treatments required did not vary between the waves except for a decrease in antibiotic use with each subsequent wave (P < .0001). The impact of COVID-19 on the pediatric population differs from the adult population, and the overall number of hospitalized children has mirrored the peak in cases observed during each infection wave. Our study illustrates the changes in clinical presentation and severity observed with the different coronavirus variants.

Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

The impact of COVID on bacterial sepsis.

PURPOSE: To identify the predictors of morbidity and mortality in matched COVID-19 positive and negative patients who were septic with Gram positive or Gram negative infections. METHODS: We conducted a retrospective review, from March to October 2020, of matched septic patients at five Hackensack Meridian Health hospitals who had bacteremia with Staphylococcus aureus, Klebsiella pneumoniae or Escherichia coli with and without COVID-19. We extracted patient demographics, comorbidities and clinical outcomes data using ICD-10 codes. Bacterial isolates were compared by whole genome sequencing analysis. Multivariate logistic regression was used to analyze independent predictors of morbidity and mortality. RESULTS: A total of 208 patients were grouped by positive bloodstream infection (BSI) with COVID-19 (n = 104) and without COVID-19 (n = 104). Most patients were over age 50 (90% vs. 89%) and Caucasian (78% vs. 86%). Inpatient mortality was higher in patients with COVID-19 for both GP (35% vs. 8%, p < 0.05) and GN (28% vs. 10%, p < 0.05) BSIs. Patients with Gram positive (GP) BSIs had a significant increase in mortality risk (OR 4.5, CI 1.4-14.5, p < 0.05) in contrast to those with Gram negative (GN) infections (OR 0.4, CI 0.4-4.0, p = 0.4). CONCLUSION: Concurrent COVID-19 infection is associated with a significant increase in morbidity and mortality in patients with GP and GN BSIs. Patients with S. aureus BSIs with COVID-19 are more likely to develop shock and respiratory failure and have higher rates and odds of mortality than those without COVID-19. These findings provide an essential insight into the care of these patients, especially those co-infected with Staphylococcus aureus.

The Feasibility and Impact of a Postresuscitation Care Protocol in the Well Baby Nursery.

OBJECTIVE: The objective of this study is to determine if a postresuscitation care (PRC) protocol in the well baby nursery (WBN) would improve identification of infants requiring neonatal intensive care unit (NICU) admission. STUDY DESIGN: This is a retrospective and prospective cohort study of a PRC protocol in 765 WBN admissions after delivery room (DR) resuscitation with continuous positive airway pressure and/or positive pressure ventilation. RESULTS: After protocol initiation, NICU transfers during the birth hospitalization increased significantly (11.17 vs. 16.08%, p < 0.05). There was no difference in incidence of NICU transfer (5.99 vs. 7.29%, pre-PRC vs. PRC, p = 0.47) during the first 4 hours of life during protocol administration. Respiratory distress was the most common indication for NICU transfer in both cohorts (7.90 vs. 11.81%, p = 0.09, pre-PRC vs. PRC). Noninvasive positive pressure and/or high-flow nasal cannula (5.72 vs. 9.55%, p = 0.06, pre-PRC vs. PRC) were routinely administered in the NICU to transferred infants. CONCLUSION: After apparent recovery from DR resuscitation, WBN admissions experience significant risk of complications requiring NICU transfer, supporting Neonatal Resuscitation Program recommendation for enhanced monitoring. In our study, we demonstrated the feasibility of standardized PRC protocol in the WBN. NICU transfers increased after initiation of a PRC protocol; however, further studies are needed to confirm possible benefits of this PRC protocol in improving identification of infants requiring a higher level of care. KEY POINTS: · A PRC protocol in WBN is feasible and associated with increased NICU transfer.. · Despite initial apparent recovery, delayed presentation of respiratory distress is a frequent morbidity.. · Increased surveillance as recommended by Neonatal Resuscitation Program is indicated in this population..