Serum antibodies develop upon infection with SARS-CoV-2 and are currently used to stratify donors of convalescent plasma and assess the prevalence of COVID-19. This study examines the use of serum antibodies to SARS-CoV-2 spike protein in the diagnosis of COVID-19.

NK cells regulate CD4+ and CD8+ T cells in acute viral infection, vaccination, and the tumor microenvironment. NK cells also become exhausted in chronic activation settings. The mechanisms causing these ILC responses and their impact on adaptive immunity are unclear. CD8+ T cell exhaustion develops during chronic Toxoplasma gondii ( T. gondii ) infection resulting in parasite reactivation and death. How chronic T. gondii infection impacts the NK cell compartment is not known. We demonstrate that NK cells do not exhibit hallmarks of exhaustion. Their numbers are stable and they do not express high PD1 or LAG3. NK cell depletion with anti-NK1.1 is therapeutic and rescues chronic T. gondii infected mice from CD8+ T cell exhaustion dependent death, increases survival after lethal secondary challenge and alters cyst burdens in brain. Anti-NK1.1 treatment increased polyfunctional CD8+ T cell responses in spleen and brain and reduced CD8+ T cell apoptosis in spleen. Chronic T. gondii infection promotes the development of a modified NK cell compartment, which does not exhibit normal NK cell characteristics. NK cells are Ly49 and TRAIL negative and are enriched for expression of CD94/NKG2A and KLRG1. These NK cells are found in both spleen and brain. They do not produce IFNγ, are IL-10 negative, do not increase PDL1 expression, but do increase CD107a on their surface. Based on the NK cell receptor phenotype we observed NKp46 and CD94-NKG2A cognate ligands were measured. Activating NKp46 (NCR1-ligand) ligand increased and NKG2A ligand Qa-1b expression was reduced on CD8+ T cells. Blockade of NKp46 rescued the chronically infected mice from death and reduced the number of NKG2A+ cells. Immunization with a single dose non-persistent 100% protective T. gondii vaccination did not induce this cell population in the spleen, suggesting persistent infection is essential for their development. We hypothesize chronic T. gondii infection induces an NKp46 dependent modified NK cell population that reduces functional CD8+ T cells to promote persistent parasite infection in the brain. NK cell targeted therapies could enhance immunity in people with chronic infections, chronic inflammation and cancer.

OBJECTIVEThe extent of resection has been shown to improve outcomes in patients with meningiomas. However, resection can be complicated by constraining local anatomy, leading to subtotal resections. An understanding of the natural history of residual tumors is necessary to better guide postsurgical management and minimize recurrence. This study seeks to identify predictors of recurrence and high growth rate following subtotal resection of intracranial meningiomas.METHODSAdult patients who underwent primary surgical resection of a WHO grade I meningioma at a tertiary care institution from 2007–2017 were retrospectively reviewed. Volumetric tumor measurements were made on patients with subtotal resections. Stepwise multivariate proportional hazards regression analyses were performed to identify factors associated with time to recurrence, as well as stepwise multivariate regression analyses to assess for factors associated with high postoperative growth rate.RESULTSOf the 141 patients (18%) who underwent radiographic subtotal resection of an intracranial meningioma during the reviewed period, 74 (52%) suffered a recurrence, in which the median (interquartile range, IQR) time to recurrence was 14 (IQR 6–34) months. Among those tumors subtotally resected, the median pre- and postoperative tumor volumes were 17.19 cm3 (IQR 7.47–38.43 cm3) and 2.31 cm3 (IQR 0.98–5.16 cm3), which corresponded to a percentage resection of 82% (IQR 68%–93%). Postoperatively, the median growth rate was 0.09 cm3/year (IQR 0–1.39 cm3/year). Factors associated with recurrence in multivariate analysis included preoperative tumor volume (hazard ratio [HR] 1.008,95% confidence interval [CI] 1.002–1.013, p = 0.008), falcine location (HR 2.215, 95% CI 1.179–4.161, p = 0.021), tentorial location (HR 2.410, 95% CI 1.203–4.829, p = 0.024), and African American race (HR 1.811, 95% CI 1.042–3.146, p = 0.044). Residual volume (RV) was associated with high absolute annual growth rate (odds ratio [OR] 1.175, 95% CI 1.078–1.280, p < 0.0001), with the maximum RV benefit at < 5 cm3 (OR 4.056, 95% CI 1.675–9.822, p = 0.002).CONCLUSIONSBy identifying predictors of recurrence and growth rate, this study helps identify potential patients with a high chance of recurrence following subtotal resection, which are those with large preoperative tumor volume, falcine location, tentorial location, and African American race. Higher RVs were associated with tumors with higher postoperative growth rates. Recurrences typically occurred 14 months after surgery.

Background Caregivers provide critical support for patients with chronic diseases, including heart disease, but often experience caregiver stress that negatively impacts their health, quality of life, and patient outcomes. We aimed to inform health care teams on an evidence‐based approach to supporting the caregivers of patients with heart disease. Methods and Results We conducted a systematic review and meta‐analysis of randomized controlled trials written in English that evaluated interventions to support caregivers of patients with heart disease. We identified 15,561 articles as of April 2, 2020 from 6 databases; of which 20 unique randomized controlled trials were evaluated, representing a total of 1570 patients and 1776 caregivers. Most interventions focused on improving quality of life, and reducing burden, depression, and anxiety; 85% (17 of 20) of the randomized controlled trials provided psychoeducation for caregivers. Interventions had mixed results, with moderate non‐significant effects observed for depression (Hedges’ g=−0.64; 95% CI, −1.34 to 0.06) and burden (Hedges’ g=−0.51; 95% CI, −2.71 to 1.70) at 2 to 4 months postintervention and small non‐significant effects observed for quality of life and anxiety. These results were limited by the heterogeneity of outcome measures and intervention delivery methods. A qualitative synthesis of major themes of the interventions resulted in clinical recommendations represented with the acronym “CARE” (Caregiver‐Centered, Active engagement, Reinforcement, Education). Conclusions This systematic review highlights the need for greater understanding of the challenges faced by caregivers and the development of guidelines to help clinicians address those challenges. More research is necessary to develop clinical interventions that consistently improve caregiver outcomes.