Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection.

Background: With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. Methods: This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. Results: CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001). Conclusion: Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.

Diagnostic Value of Natural Killer Cells, CD56+ CD16+ Natural Killer Cells, NLRP3, and Lactate Dehydrogenase in Severe/Critical COVID-19: A Prospective Longitudinal Study According to the Severe/Critical COVID-19 Definitions.

Innate immunity, as the first line of defense of our immune system, plays a crucial role in defending against SARS-CoV-2 infection and also its immunopathogenesis. We aim to investigate the immune status of natural killer (NK) cells, natural killer T (NKT) cells, and NLRP3 gene expression in COVID-19 patient blood samples. The immunophenotype of NK cell subsets and NKT cells was detected by flow cytometry and the expression of NLRP3 gene assessed by reverse transcriptase real-time polymerase chain reaction in 44 COVID-19 patients and 20 healthy individuals. The percentage of most of NK cell subpopulation and NKT cells was significantly decreased in COVID-19 patients. The percentage of CD56dim CD16- NK cell subsets, and NLRP3 gene expression increased. The percentage of total NK cells, CD56+ CD16+ NK cells, and NLRP3 gene expression had acceptable sensitivity and specificity for assisting diagnosis of severe/critical COVID-19. O2 saturation% and lactate dehydrogenase levels showed valuable diagnostic value to identify critical cases. The declined NK and NKT cells in COVID-19 patients and enhanced NLRP3 gene expression were associated with disease severity. Total NK cells, CD56+ CD16+ NK cells, and NLRP3 gene expression might be used as meaningful indicators for assisting diagnosis of severe/critical COVID-19.

COVID-19-associated mucormycosis: A review of an emergent epidemic fungal infection in the era of COVID-19 pandemic.

At a time when the COVID-19's second wave is still picking up in countries like India, a number of reports describe the potential association with a rise in the number of cases of mucormycosis, commonly known as the black fungus. This fungal infection has been around for centuries and affects those people whose immunity has been compromised due to severe health conditions. In this article, we provide a detailed overview of mucormycosis and discuss how COVID-19 could have caused a sudden spike in an otherwise rare disease in countries like India. The article discusses the various symptoms of the disease, class of people most vulnerable to this infection, preventive measures to avoid the disease, and various treatments that exist in clinical practice and research to manage the disease.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

The effectiveness of gabapentin and gabapentin/montelukast combination compared with dextromethorphan in the improvement of COVID-19- related cough: A randomized, controlled clinical trial.

INTRODUCTION: Cough is one of the most common presenting symptoms of COVID-19, which can persist for weeks or months. OBJECTIVE: The goal of this study was to evaluate the effectiveness of gabapentin (GBT) alone and in combination with montelukast (MTL) for improving cough. METHODS: In this open-label randomized controlled clinical trial, eligible cases were patients hospitalized with moderate to severe COVID-19 who had cough with a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 2 based on its cough subscale. The participants were randomly assigned to three groups including two experimental groups and one control group. The first and second experimental groups received GBT and GBT/MTL, respectively, whereas the control group received dextromethorphan (DXM). Treatment duration was 5 days in all groups. Before and after the interventions, the severity of cough was evaluated using BCSS scale and Visual Analog Scale (VAS). RESULTS: A total of 180 patients were included; GPT, GPT/MTL, and DXM consisted of 76, 51, and 53 patients, respectively. There was no significant difference between the three groups in terms of age, gender, and comorbidities (P > 0.05). Regarding BCSS and VAS scores, there was significant reduction from the baseline values in all groups (P < 0.0001), with the change rate being significantly higher in DXM group. The amount of reduction of BCSS in the GPT/MTL group was significantly more than the GPT group, whereas there was no significant difference between the two groups regarding VAS score. Although the duration of hospitalization differed between the groups with the GPT/MTL group having the shortest duration, the difference was statistically significant only between the GPT and GPT/MTL groups (P < 0.0001). CONCLUSION: GPT, both alone and in combination with MTL, improves cough frequency and severity in hospitalized patients with COVID-19, with the combination being more efficacious. This regimen may be useful in patients who cannot tolerate opioids.

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial.

BACKGROUND: COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19. METHODS: Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days. RESULTS: Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025). CONCLUSION: The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indices, including biochemical and clinical indices. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20121216011763N46 . 2020-10-31.

Hemoperfusion in patients with severe COVID-19 respiratory failure, lifesaving or not?

BACKGROUND: The new coronavirus outbreak quickly filled hospital beds and stunned the world. Intensive care is required for 5% of patients, and the mortality rate for critically ill patients is 49%. The "cytokine storm" is considered as the main cause of pathogenesis for coronavirus disease-19 (COVID-19)-related respiratory failure, hemoperfusion may be a modality for treatment of disease. MATERIALS AND METHODS: Thirty-seven an patients with positive real-time polymerase chain reaction for SARStions2 in an upper respiratory tract sample or typical chest computed tomography lesion were eligible for this case-control study. Patients meeting the criteria for hemoperfusion including clinical and laboratory indices, were evaluated for outcomes such as hospitalization length and mortality. Patients were divided into three groups, i.e., patients who received hemoperfusion without a need for mechanical ventilation (MV), patients who received hemoperfusion before MV, and patients who received hemoperfusion after MV. RESULTS: Among 37 patients with COVID-19 respiratory failure, 32% were female with a mean age of 55.54 (standard deviation 14.1) years. There was no statistically significant difference between the three groups in terms of length of hospital stay and intensive care unit (ICU) stay (P-tayns: 0.593 and 0.243, respectively, confidence interval [CI]: 95%). Heart rate, respiratory rate, PaO2/FIO2, high-sensitivity C-reactive protein, and ferritin significantly improved after the application of hemoperfusion in all groups (P < 0.05, CI: 95%). CONCLUSION: It seems that applying hemoperfusion in the inflammatory phase of the disease, especially before the intubation, reduce the need for MV. However, hemoperfusion does not have any impacts on the duration of hospital and ICU stay.

Rhabdomyolysis plus Hypocalcemia and Diabetic Ketoacidosis as Concurrent Rare COVID-19 Manifestations.

BACKGROUND: Common manifestations of coronavirus disease 2019 (COVID-19) from its initial official introduction are mostly related to the respiratory system. However, other rarer presentations are reported nowadays. Case Presentations. We reported three cases of COVID-19-infected patients with rhabdomyolysis as well as two other rarer simultaneous signs, including hypocalcemia (Case 1) and diabetic ketoacidosis (DKA) (Case 2). CONCLUSION: Despite the fact that rhabdomyolysis is an infrequent manifestation of COVID-19, high clinical suspicion is required for proper diagnosis and management of this disease as well as other concurrent rarer presentations, including hypocalcemia and DKA for the prevention of further complications.

The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to assess the effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19). TRIAL DESIGN: This is a Double-Blind, Placebo-Controlled, Parallel Arm, Randomized Phase ΙΙ Clinical Trial. PARTICIPANTS: Patients with the confirmed COVID-19 based on the PCR test are eligible to participate in the trial if they are 18 to 75 years of age and have no history of the current use of warfarin or propolis supplement and presence of sensitivity to bee products. Patients will be recruited from the Al-Zahra hospital in Isfahan city, Isfahan, Iran. INTERVENTION AND COMPARATOR: Participants (N=40) in the intervention group will receive an identical propolis tablet (containing 300 mg Iranian green propolis extract) three times a day for a period of 2 weeks. Participants (N=40) in the control group will receive an identical placebo tablet (containing 300 mg microcrystalline cellulose) three times a day for 2 weeks. All tablets are prepared by the Reyhan Naghsh Jahan Pharmaceutical Co., Isfahan, Iran. MAIN OUTCOMES: The main outcomes are changes in the coronavirus disease's clinical symptoms including duration and severity from baseline to the end of 2 weeks. RANDOMIZATION: Eligible patients will be randomly allocated in a 1:1 ratio to the intervention or control group. Randomization will be performed on the basis of permuted block sizes of 4 and will be stratified according to sex categories. Randomization sequences will be prepared by the trial's pharmacist with the use of random-number tables. BLINDING (MASKING): The trial-group assignment will be concealed from all participants, clinicians, and investigators throughout the trial. To ensure blinding, randomization sequences will be kept in identical, opaque, sealed, sequentially numbered envelopes. Only the trial's pharmacist has access to the randomization list. Also, the placebo tablet will be similar to the propolis tablet in terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labelling, and packaging. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The calculated total sample size is 80 patients, with 40 patients in each group. TRIAL STATUS: The protocol is Version 1.0, October 10, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by March 21, 2021. TRIAL REGISTRATION: The name of the trial register: The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial. IRCT registration number: IRCT20200802048267N1 . Date of trial registration: 20 October 2020, retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial.

Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died.Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate)were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure.