Effects of a booster dose of BNT162b2 on spike-binding antibodies to SARS-CoV-2 Omicron BA.2, BA.3, BA.4 and BA.5 subvariants in infection-naïve and previously-infected individuals.

It has been demonstrated that after two doses, SARS-CoV-2 mRNA vaccine-induced neutralizing antibodies against Omicron subvariants are much lower than against wild type virus and a booster dose greatly increases Omicron neutralization. We compared Spike-binding IgG responses against wild type virus and four SARS-CoV-2 Omicron subvariants in infection-naïve and previously-infected (hybrid immunity) individuals after the second and the third (booster) dose of BNT162b2. In both groups of individuals, antibodies for all four Omicron subvariants were lower than wild type antibodies. Compared to infection-naïve individuals, hybrid immunity resulted in higher antibodies levels after 2 doses of vaccine but not after the booster. In both groups, antibodies for wild type and all Omicron subvariants waned over an 8-month period post second dose but rebounded after the booster. These results underscore the importance of boosters to restore diminishing antibody levels for both infection-naïve and previously-infected individuals.

ISSLS PRIZE in Clinical Science 2022: Epidemiology, risk factors and clinical impact of juvenile Modic changes in paediatric patients with low back pain.

PURPOSE: It's a long-held belief that Modic changes (MC) occur only in adults, with advanced age, and are highly associated with pain and adverse outcomes. The following study addressed the epidemiology, risk factors and clinical relevance of MC in young paediatric patients. METHODS: Two hundred and seven consecutive patients with no history of deformities, neoplasms, trauma, or infections were included in this ambispective study. MRIs were utilized to assess MCs and types, and other degenerative disc/endplate abnormalities. Subject demographics, duration of symptoms, clinic visits, conservative management (physical therapy, NSAIDs, opioids, injections) and surgery were noted. RESULTS: The mean age was 16.5 years old (46.9% males), 14% had MCs and they occurred throughout the spine. Subject baseline demographics were similar between MCs and non-MCs patients (p > 0.05). Modic type 2 (50%) was the most common type (type 1:27.1%; type 3:18.8%; mixed:4.7%). Multivariate analyses noted that endplate damage (OR: 11.36), disc degeneration (OR: 5.81), disc space narrowing (OR: 5.77), Schmorl's nodes (OR: 4.30) and spondylolisthesis (OR: 3.55) to be significantly associated with MCs (p < 0.05). No significant differences in conservative management were noted between Modic and non-MCs patients (p > 0.05). Among surgery patients (n = 44), 21% also had MCs (p = 0.134). Symptom-duration was significantly greater in MC patients (p = 0.049). CONCLUSION: Contrary to traditional dogma, robust evidence now exists noting that MCs and their types can develop in children. Our findings give credence to the "Juvenile" variant of MCs, whereby its implications throughout the lifespan need to be assessed. Juvenile MCs have prolonged symptoms and related to specific structural spine phenotypes.

IL-33-mediated Eosinophilia Protects against Acute Lung Injury.

Pneumonia-induced lung injury and acute respiratory distress syndrome can develop because of an inappropriate inflammatory response to acute infections, leading to a compromised alveolar barrier. Recent work suggests that hospitalized patients with allergies/asthma are less likely to die of pulmonary infections and that there is a correlation between survival from acute respiratory distress syndrome and higher eosinophil counts; thus, we hypothesized that eosinophils associated with a type 2 immune response may protect against pneumonia-induced acute lung injury. To test this hypothesis, mice were treated with the type 2-initiating cytokine IL-33 intratracheally 3 days before induction of pneumonia with airway administration of a lethal dose of Staphylococcus aureus. Interestingly, IL-33 pretreatment promoted survival by inhibiting acute lung injury: amount of BAL fluid proinflammatory cytokines and pulmonary edema were both reduced, with an associated increase in oxygen saturation. Pulmonary neutrophilia was also reduced, whereas eosinophilia was strongly increased. This eosinophilia was key to protection; eosinophil reduction eliminated both IL-33-mediated protection against mortality and inhibition of neutrophilia and pulmonary edema. Together, these data reveal a novel role for eosinophils in protection against lung injury and suggest that modulation of pulmonary type 2 immunity may represent a novel therapeutic strategy.

Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils.

The dysregulated, unbalanced immune response of sepsis results in a mortality exceeding 20%, yet recent findings by our group indicate that patients with allergic, type 2-mediated immune diseases are protected from developing sepsis. We evaluated CD4+ Th cell polarization among patients with Staphylococcus aureus bacteremia and confirmed that survivors had a higher percentage of circulating Th2 cells but lower frequencies of Th17 cells and neutrophils early in the course of infection. To establish the mechanism of this protection, we used a mouse model of lethal S. aureus bacteremia and found that intratracheal pretreatment with the type 2-initiating cytokine IL-33 activated pulmonary type 2 innate lymphoid cells (ILC2s) and promoted eosinophilia. In addition, stimulation of type 2 immunity before lethal infection suppressed the pulmonary neutrophilic response to S. aureus. Mice lacking functional ILC2s did not respond to IL-33 and were not protected from lethal bacteremia, but treatment of these mice with the type 2 cytokines IL-5 and IL-13 rescued them from death. Depletion of eosinophils abrogated IL-33-mediated protection, indicating that eosinophilia is also necessary for the survival benefit. Thus, we have identified a potentially novel mechanism by which type 2 immunity can balance dysregulated septic inflammatory responses, thereby clarifying the protective benefit of type 2 immune diseases on sepsis mortality.