A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis

Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because of its potential to cause life-threatening Covid-19 disease. By comparison to paucisymptomatic virus clearance by most individuals, Covid-19 has been proposed to reflect insufficient and/or pathologically exaggerated immune responses. Here we identify a consensus peripheral blood immune signature across 63 hospital-treated Covid-19 patients who were otherwise highly heterogeneous. The core signature conspicuously blended adaptive B cell responses typical of virus infection or vaccination with discrete traits hitherto associated with sepsis, including monocyte and dendritic cell dampening, and hyperactivation and depletion of discrete T cell subsets. This blending of immuno-protective and immuno-pathogenic potentials was exemplified by near-universal CXCL10/IP10 upregulation, as occurred in SARS1 and MERS. Moreover, specific parameters including CXCL10/IP10 over-expression, T cell proliferation, and basophil and plasmacytoid dendritic cell depletion correlated, often prognostically, with Covid-19 progression, collectively composing a resource to inform SARS-CoV-2 pathobiology and risk-based patient stratification.

Differentiating PTSD from anxiety and depression: Lessons from the ICD-11 PTSD diagnostic criteria.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is frequently associated with depression and anxiety, but the nature of the relationship is unclear. By removing mood and anxiety diagnostic criteria, the 11th edition of the International Classification of Diseases (ICD-11) aims to delineate a distinct PTSD phenotype. We examined the effect of implementing ICD-11 criteria on rates of codiagnosed depression and anxiety in survivors with recent PTSD. METHOD: Participants were 1,061 survivors of traumatic injury admitted to acute care centers in Israel. ICD-10 and ICD-11 diagnostic rules were applied to the Clinician-Administered PTSD Scale for DSM-IV. Co-occurring disorders were identified using the Structured Clinical Interview for DSM-IV (SCID). Depression severity was measured by the Beck Depression Inventory-II (BDI-II). Assessments were performed 0-60 ("wave 1") and 90-240 ("wave 2") days after trauma exposure. RESULTS: Participants identified by ICD-11 PTSD criteria were equally or more likely than those identified by the ICD-10 alone to meet depression or anxiety disorder diagnostic criteria (for wave 1: depressive disorders, OR [odds ratio] = 1.98, 95% CI [confidence interval] = [1.36, 2.87]; anxiety disorders, OR = 1.04, 95% CI = [0.67, 1.64]; for wave 2: depressive disorders, OR = 1.70, 95% CI = [1.00, 2.91]; anxiety disorders, OR = 1.04, 95% CI = [0.54, 2.01]). ICD-11 PTSD was associated with higher BDI scores (M = 23.15 vs. 17.93, P < 0.001 for wave 1; M = 23.93 vs. 17.94, P < 0.001 for wave 2). PTSD symptom severity accounted for the higher levels of depression in ICD-11 PTSD. CONCLUSIONS: Despite excluding depression and anxiety symptom criteria, the ICD-11 identified equal or higher proportion of depression and anxiety disorders, suggesting that those are inherently associated with PTSD.

Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over.

PURPOSE OF REVIEW: One begins to see improvement in glycemic measures and triglycerides with small amounts of weight loss, but with greater levels of weight loss there is even greater improvement. In fact, the relationship between weight loss and glycemia is one that is very close. RECENT FINDINGS: This is fortunate for diabetes prevention; it takes only small amounts of weight loss to prevent progression to type 2 diabetes from impaired glucose tolerance, and after the 10 kg of weight loss, one cannot demonstrate much additional improvement in risk reduction. Modest weight loss (5 to 10%) is also associated with improvement in systolic and diastolic blood pressure and HDL cholesterol. With all these risk factors, more weight loss produces more improvement. Further, for patients with higher BMI levels (>40 kg/m2), the ability to lose the same proportion of weight with lifestyle intervention is equal to that of those with lower BMI levels, and there is equal benefit in terms of risk factor improvement with modest weight loss. For some comorbid conditions, more weight loss is needed-10 to 15%-to translate into clinical improvement. This is true with obstructive sleep apnea and non-alcoholic steatotic hepatitis. There is a graded improvement in improvements in measures of quality of life, depression, mobility, sexual dysfunction, and urinary stress incontinence, whereby improvements are demonstrable with modest weight loss (5-10%) and with further weight loss there are further improvements. For polycystic ovarian syndrome and infertility, modest weight loss (beginning at 2-5%) can bring improvements in menstrual irregularities and fertility. Moderate weight loss (5-10%) has been shown to be associated with reduced health care costs. Reduction in mortality may take more than 10% weight loss, although definitive studies have not been done to demonstrate that weight loss per se is associated with mortality reduction. Clinicians in medical weight management should bear in mind that the target should be health improvement rather than a number on the scale. The individual patient's targeted health goal should be assessed for response rather than a prescribed percentage weight loss.