Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity.Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed.Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1β, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven.Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Am J Psychiatry 167:12, December 2010 ajp.psychiatryonline.org 1. Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M: S-Adenosyl methionine (SAME) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 2010; 167:942-948

Background: Serratia marcescens (SM) is a Gram-negative pathogen discovered by Italian pharmacist, Bizio, in 1819. According to the literature, S. marcescens is resistant to a wide range of antibiotics, including penicillin, cephalosporin, tetracycline, macrolide, nitrofurantoin, and colistin. We conducted a systematic review of published reports, determined what invasive infections could cause SM, and established the most appropriate antibiotic therapy. Methods: We registered this systematic review on the PROSPERO registry of systematic reviews–meta-analyses before we started our research (registration number CRD42022323159). The online searches of published studies were implemented via MEDLINE, the Cochrane Central Register of Controlled Trials, EBSCO, Scopus, Google Scholar, SCIndex, and the registry of clinical studies of human participants (ClinicalTrials.gov). Results: Our study included 32 published articles (9 case series and 23 case reports). There were 57 individual cases, respectively. The oldest patient was 97 years and the youngest patient was a newborn. S. marcescens was, in most cases, isolated from blood followed by urine and cerebrospinal fluid. In most cases, sensitivity was tested to cotrimoxazole (from 27 isolates, 10 showed resistance) followed by gentamicin (from 26 isolates, 3 showed resistance) as well as amikacin (from 21 isolates, none showed resistance). Patients died from an infection in 21 cases (31%). Conclusions: Treatment of SM infections should include carbapenems or aminoglycosides in combination with third-generation (and eventually fourth-generation) cephalosporin. Cotrimoxazole should be considered in cases of uncomplicated urinary infections.