Does therapeutic plasma exchange have a role in resistant cytokine storm state of COVID-19 infection?

Introduction: Among the main causes of mortality in COVID-19 patients is cytokine storm (CS) state. Few treatment options with variable efficacy results are available for its management. We aimed to illustrate the efficacy of Therapeutic Plasma Exchange (TPE) treatment in COVID-19 patients with resistant CS.Material and methods: This research is a prospective pilot study which included ten COVID-19 positive patients with CS state with no response after two doses of tocilizumab. Each patient received three to five TPE sessions according to his/her response. Respiratory status {oxygen (O2) requirements and data of mechanical ventilation} and laboratory markers (IL-6, CRP, ferritin, D dimer, LDH) were assessed before and after TPE. We reported mortality at 28 day of illness.Results: Six males and four females were enrolled in the study with a mean age of (52.9 years). Seven patients (70%) were on mechanical ventilation (MV). After TPE, oxygenation parameters and most laboratory markers improved significantly in all patients (p < 0.05). Four patients survived and were discharged (40%). One was on MV and three were not. The four patients had better hypoxic index (PaO2/FiO2 ratio) (˃100 vs <100), started TPE sooner after tocilizumab failure (2–3 vs 5–6 days), needed fewer TPE sessions (3 vs 4–5, p = 0.03), and less duration in ICU (6.5 vs 12.5 days) compared to those who did not benefit.Conclusions: In patients with CS state who did not respond well to tocilizumab and steroids, TPE could be a good option. Larger randomized clinical trials are needed to support its use.Clinical trials registration: ClinicalTrials.gov Identifier:NCT0445734

COVID-19 versus H1N1: challenges in radiological diagnosis - comparative study on 130 patients using chest HRCT

Background: During the current second wave of COVID-19, the radiologists are expected to face great challenges in differentiation between COVID-19 and other virulent influenza viruses, mainly H1N1. Accordingly, this study was performed in order to find any differentiating CT criteria that would help during the expected clinical overlap during the current Influenza season. Results: This study was retrospectively conducted during the period from June till November 2020, on acute symptomatic 130 patients with no history of previous pulmonary diseases; 65 patients had positive PCR for COVID-19 including 50 mild patients and 15 critical or severe patients; meanwhile, the other 65 patients had positive PCR for H1N1 including 50 mild patients and 15 critical or severe patients. They included 74 males and 56 females (56.9%:43.1%). Their age ranged 14–90 years (mean age 38.9 ± 20.3 SD). HRCT findings were analyzed by four expert consultant radiologists in consensus. All patients with COVID-19 showed parenchymal or alveolar HRCT findings; only one of them had associated airway involvement. Among the 65 patients with H1N1; 56 patients (86.2%) had parenchymal or alveolar HRCT findings while six patients (9.2%) presented only by HRCT signs of airway involvement and three patients (4.6%) had mixed parenchymal and airway involvement. Regarding HRCT findings of airway involvement (namely tree in bud nodules, air trapping, bronchial wall thickening, traction bronchiectasis, and mucous plugging), all showed significant p value (ranging from 0.008 to 0.04). On the other hand, HRCT findings of parenchymal or alveolar involvement (mainly ground glass opacities) showed no significant relation. Conclusion: HRCT can help in differentiation between non-severe COVID-19 and H1N1 based on signs of airway involvement

H1N1 viral pneum

Influenza viruses are common and important pathogens affecting human. Seasonal epidemics and unpredictable pandemics associated with influenza A (“swine” influenza or H1N1) virus had been declared by the World Health Organization (WHO), last one on June 11, 2009. Clinically, wide range of illness was described ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS) complicated by multi-organ failure. Vulnerable groups showed high risk for morbidity and mortality. Radiologically, also wide range of chest HRCT findings were described including sub-centimeter air-space nodules, patchy ground-glass opacities and air-space consolidations. Diffuse alveolar damage (DAD) and ARDS were considered to be the end result. Aim of study was to evaluate different patterns and imaging findings associated with H1N1 lung infection using MSCT of the chest. Aim of the work: The aim of study was to evaluate different patterns and imaging findings associated with H1N1 lung infection using MSCT of the chest. Methods: This study was conducted on 50 patients from September 2013 till February 2016. All patients were examined by multi-detector computed tomography (MDCT). Results: HRCT findings associated with H1N1 chest infection can overlap and range from mild cases with patchy ground glass opacities (with or without crazy paving pattern) up to air space consolidations, alveolar hemorrhage, diffuse alveolar damage (DAD) and ARDS. Manifestation of bronchiolitis obliterans was also detected including mucous plugging, mosaic attenuation with mixed air trapping and ground glass opacities (head cheese pattern) and bronchiectasis. Conclusion: MDCT picture of H1N1 chest infection is highly variable with a spectrum of HRCT findings ranging from focal patchy ground glass attenuation to diffuse alveolar damage (DAD) or adult respiratory distress syndrome (ARDS). Still, constellation of clinical data and HRCT findings especially in endemic areas can raise the suspicion of H1N1

Role of C-reactive protein and interleukin-6 in predicting the prognosis of ICU-admitted patients with acute exacerbation of COPD

Background and Objective: Chronic obstructive pulmonary disease (COPD) is a leading and increasing cause of worldwide morbidity and mortality. No universal predictor of mortality and outcome was defined especially in intensive care unit (ICU)-admitted patients with acute exacerbation of COPD (AECOPD). The objective was to detect the possible role of C-reactive protein (CRP) and interleukin-6 (IL-6) levels in predicting the prognosis of ICU-admitted patients with AECOPD. Methods: This prospective cohort study enrolled 50 adult patients with AECOPD who were admitted in the ICU. Serum CRP and IL-6 levels were measured on admission. The primary endpoint was any-cause mortality during ICU stay or 28 days after discharge. Lengths of ICU and hospital stay besides complications encountered were recorded. Results: Serum CRP level was significantly elevated in patients with prolonged mechanical ventilation (MV) days, ICU stay and hospital stay (r = 0.406, p = 0.007; r = 0.411, p = 0.006; r = 0.387, p = 0.010, respectively). Similar results were noted for serum IL-6 level (r = 0.554, p=<0.001; r = 0.533, p=<0.001; r = 0.508, p = 0.001, respectively). Combined CRP and IL-6 serum levels predicted 28 day mortality at a cut-off value of 110 mg/dl and 347.8 pg/ml respectively (AUC = 0.851, p = 0.006) with 83.33% sensitivity, 75.68% specificity, 35.71% PPV and 96.55% NPV. This was significantly greater than that for CRP alone (p = 0.040) or IL-6 alone (p = 0.004). Conclusions: Serum levels of CRP and IL-6 (either individually or combined) were useful markers in predicting the mortality, complications and outcome in ICU-admitted patients with AECOPD

Sputum–plasma ratio of soluble receptor for advanced glycation end-products in patients with chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammatory consequences. Receptor for advanced glycation end products (RAGE) acts as an important progression factor amplifying the immune and inflammatory responses in several pathophysiological conditions. The soluble form of RAGE (sRAGE) acts as a decoy for the receptor ligands and is thus thought to protect against excessive inflammation. Conflicting reports exist about sRAGE value in stable and exacerbating COPD. Objective: To assess the sputum to plasma ratio of sRAGE in stable COPD patients. Subjects and methods: The study included 44 adult patients of both sexes who were presented to Alexandria Main University Hospital between March and July 2015. Patients were categorized into three groups; 15 stable COPD patients (Group I), 15 smokers without COPD (Group II), and 14 healthy non-smokers (Group III). Measurement of sRAGE level in induced sputum and plasma was performed using ELISA technique. Results: The study included 38 male patients and 6 female patients, whose median ages were 50, 42 and 35.5 years in Groups I, II, and III respectively (p < 0.001). Median FEV1% predicted were 35, 96, and 105% in Groups I, II, and III respectively (p < 0.001). No statistical significant difference was found among all groups regarding sRAGE level in induced sputum, plasma or sputum/plasma ratio (p = 0.092, 0.372, 0.154, respectively). Although levels of sRAGE is apparently higher in induced sputum rather than in plasma, it lacked significance (r = 0.27, p = 0.08). Furthermore, no significant correlation was found between either plasma or sputum sRAGE level and predicted FEV1% (r = −0.11, p = 0.48 and r = −0.12, p = 0.28, respectively). Conclusions: sRAGE level either in induced sputum, plasma or sputum plasma ratio is not significantly different between stable COPD patients, smokers and healthy controls. Thus, sRAGE cannot be considered as a marker of either diagnosis or severity of COPD

The role of supplementary vitamin D in treatment course of pulmonary tuberculosis

Background: Vitamin D insufficiency/deficiency is associated with impaired immune function and increased risk of active pulmonary tuberculosis (TB). Objectives: To evaluate the role of vitamin D as supplementary treatment with the first line anti-tuberculous drugs (rifampicin, izoniazide, ethambutol and pyrazinamide) in treatment course of patients with active pulmonary tuberculosis. Methods: We conducted a case-control study in El Maamora chest hospital, Alexandria governorate, Egypt, including 60 adult patients with active pulmonary TB of 30 patients each. Patients in group I (cases) received vitamin D (200,000 IU) intramuscular injection once besides anti-tuberculous drugs, while patients in group II (controls) were randomly selected from the hospital registry who received the first line anti-tuberculous treatment only. The primary outcome was evaluation of conversion time of sputum smear. The secondary outcome was clinical improvement as assessed by TB score. Measurements and main results: Mean ± SD age of all patients was 41.55 ± 14.91 years. The study included 44 (73.3%) males and 16 (26.7%) females. Vitamin D deficiency/insufficiency was detected in 54 (90%) patients. Comparing the two groups, there was a rapid decline in sputum conversion time and severity classes of TB score in group I compared to group II (p < 0.001 and p = 0.02, respectively). No complications secondary to supplementary vitamin D were met all through the study. Conclusion: Vitamin D accelerates the improvement observed in vitamin D supplemented TB therapy. Vitamin D is safe when added to anti-tuberculous drugs. Vitamin D deficiency/insufficiency is common among TB patients. Further studies are required to validate this observation and define a cut off of vitamin D level to prevent immunological alterations

Splenomegaly versus pathological lung volume during COVID-19 infection with or without cytokine storm; a linear regression analysis using CT volumetry

Background: Due to the paucity of scientific evidence, it is unclear among pulmonologists and physicians in critical care units if and when splenomegaly in novel coronavirus disease (2019) (COVID-19) patients is worrisome. This study aims to evaluate the significance of splenic volume during COVID-19 infection with or without cytokine storm and correlates splenic volume to the volume of pathological lung changes through linear regression analysis. Results: A retrospective study collected 509 polymerase chain reaction proved COVID-19 patients (399 males, 110 females; mean age 48 years, age range 24-78 years) between June and November 2021, without a history of splenic pathology. A control group of age and sex-matched 509 healthy subjects was used and analyzed according to the splenic volume. Five consulting radiologists evaluated initial and follow-up computed tomography (CT) examinations using lung CT volumetry and splenic volume calculation in consensus. Three consulting pulmonologists correlated the severity of clinical and laboratory findings, including oxygen requirements and interleukin-6 (IL-6) levels. The T test results for comparison between the COVID-19 patients and the healthy subjects control group regarding the splenic volume were significant (Tvalue was - 4.731452 and p value was 0.00002). There was no significant correlation between the severity of the disease and normal-sized spleen (26% of patients, p= 0.916) or splenomegaly (24% of patients, p= 0.579). On the other hand, all patients with a small spleen or progressive splenomegaly during serial follow-up imaging had clinically severe disease with a statistically significant correlation (p= 0.017 and 0.003, respectively). Ninety-seven percent of patients with clinically mild disease and splenomegaly had 0-20% lung involvement (CT-severity score 1) while all patients with clinically severe disease and splenomegaly had 27-73% lung involvement (CT-severity score 2 and 3) (r = 0.305, p = 0.030). Conclusions: Splenomegaly is a non-specific sign that may be found during mild and severe COVID-19 infection, it was not statistically correlated with the clinical severity and a weak positive relationship was found between the splenic size and the CT-severity score of the pathological lung volume. On the other hand, the presence of splenic atrophy or progressive splenomegaly was correlated with severe COVID-19 presentation and "cytokine storm". Therefore, the splenic volume changes should not be overlooked in COVID-19 serial CT examinations, particularly in severe or critically ill patients with cytokine storms