Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction.

The mechanisms explaining progression to severe COVID-19 remain poorly understood. It has been proposed that immune system dysregulation/over-stimulation may be implicated, but it is not clear how such processes would lead to respiratory failure. We performed comprehensive multiparameter immune monitoring in a tightly controlled cohort of 128 COVID-19 patients, and used the ratio of oxygen saturation to fraction of inspired oxygen (SpO2 / FiO2) as a physiologic measure of disease severity. Machine learning algorithms integrating 139 parameters identified IL-6 and CCL2 as two factors predictive of severe disease, consistent with the therapeutic benefit observed with anti-IL6-R antibody treatment. However, transcripts encoding these cytokines were not detected among circulating immune cells. Rather, in situ analysis of lung specimens using RNAscope and immunofluorescent staining revealed that elevated IL-6 and CCL2 were dominantly produced by infected lung type II pneumocytes. Severe disease was not associated with higher viral load, deficient antibody responses, or dysfunctional T cell responses. These results refine our understanding of severe COVID-19 pathophysiology, indicating that aberrant cytokine production by infected lung epithelial cells is a major driver of immunopathology. We propose that these factors cause local immune regulation towards the benefit of the virus.

Predictors of symptom severity in patients with chronic prostatitis and interstitial cystitis.

PURPOSE: Numerous studies have been performed to identify potential risk factors for CP/CPPS and IC. However, few studies have been done to identify predictors of disease severity. MATERIALS AND METHODS: A total of 174 men with CP/CPPS and 111 women with IC completed questionnaires to quantify symptom severity and identify demographic, medical and psychosocial characteristics. Symptom severity was assessed with the National Institutes of Health CPSI in men, and the O'Leary-Sant ICSI and problem index in women. Univariate and multivariate analyses were performed to identify characteristics predictive of worse symptoms. RESULTS: The mean National Institutes of Health CPSI score in men was 15.32, and the mean O'Leary-Sant ICSI and problem index in women was 19.17. The most commonly reported comorbidities were allergies, sinusitis, erectile dysfunction and irritable bowel syndrome in men, and allergies, urinary incontinence, sinusitis and irritable bowel syndrome in women. In the 2 sexes self-reported urinary frequency and urgency, worse depression scores and lower education level were independent predictors of worse symptom severity. In men additional independent predictors were self-reported pelvic pain, fibromyalgia and previous heart attack, and in women an additional independent predictor was postmenopausal status. CONCLUSIONS: There are several common medical conditions associated with urological pelvic pain syndromes in men and women. Few of them were predictive of symptoms severity in this analysis. Self-reported pelvic pain symptoms, education and depression severity were the factors most strongly predictive of symptom severity in patients with CP/CPPS and IC.