The effectiveness of Tocilizumab in severe covid 19 pneumonia among critically ill patients

Background: Tocilizumab, an interleukin-6 (IL-6) antagonist, is being evaluated for the management of covid-19 pneumonia. The objective of this study was to assess the effectiveness of Tocilizumab in severe covid-19 pneumonia. Method(s): This was a retrospective, observational, single centre study performed in 121 patients diagnosed with severe covid-19 pneumonia. 83 patients received standard of care treatment whereas 38 patients received tocilizumab along with standard of care. Tocilizumab was administered intravenously at 8mg/kg (upto a maximum of 800mg). The second dose of Tocilizumab was given 12 to 24 hours apart. The primary outcome measure was ICU related and hospital related mortality. The secondary outcome measures were change in clinical status of patients measured by WHO (World Health Organisation) 7 category ordinary scale, changes in interleukin-6 (IL-6) levels, secondary infections and duration of ICU stay. Result(s): Tocilizumab was administered between 3-27 days after the patient reported symptoms ( a median of 10.9 days ) and between the 1st to 3rd day of ICU admission (median of 2.1 days) . In Tocilizumab group, 16(42.1%) of 38 patients died in ICU whereas in standard of care group, 27(32.53%) of 83 patients died. The difference in clinical status assessed using WHO (World Health Organisation) 7 category ordinary scale at 28 days between Tocilizumab group and standard of care group was not statistically significant (odds ratio 1.35, 95% confidence interval 0.61 to 2.97, p = 0.44). Conclusion(s): Tocilizumab plus standard care was not superior to standard care alone in reducing mortality and improving clinical outcomes at day 28.Copyright © RJPT All right reserved.

Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Sars-Related Corona Viruses-A Challenge

SARS (Severe acute respiratory syndrome)-related corona viruses was first of all discovered 18 years ago in china from bats. Previously some study shown that bats are infected to animal kingdom and from animal this virus spread in human. As per report of identification and characterization of novel corona virus which is responsible for epidemic of acute respiratory syndrome in human beings. First of all this protein of novel SARS are seen in Wuhan city of, China in January 2020.Copyright © 2019, Advanced Scientific Research. All rights reserved.

Assessing the Extent of Covid-19 Transmission in French Guiana

Intro: The emergence of SARS-CoV-2 was accompanied by great uncertainty regarding the main epidemiological characteristics of the transmission. In a context where epidemiological surveillance was mainly targeted on symptomatic patients, we assessed the extent of SARS-CoV-2 transmission in French Guiana conducting an intra-household transmission study and population-based seroprevalence surveys repeated over time. Method(s): Household monitoring included virological and clinical follow-up for all household members for the first 28 days after the date of confirmation of the index case and serological follow-up over a 12-month period. Three seroprevalence surveys were conducted in July and September 2020 and in September 2021. Finding(s): A total of 57 dwellings including 245 individuals were included in the intra-household study. The average time between the date of onset of symptoms and the date of confirmation of diagnosis and inclusion in the study was 4.2 days and 7.2 days respectively. Secondary transmission was found in three quarters of households with a secondary infection rate of 35%. The highest transmission rate were observed in the most disadvantaged populations, within couples and from adults to children. Population-based seroprevalence studies have made it possible to monitor seroprevalence rates, which have varied from 15% at the time of the epidemic peak of the first epidemic wave to 65% of the population at the beginning of the fourth wave, despite the low impact of vaccination in French Guiana. Conclusion(s): The results obtained highlighted a high transmission of the virus in French Guiana associated with a low severity rate linked to the structure of the particularly young population. The project has provided health authorities with useful data to support prevention and control strategies and has allowed to evaluate the impact of interventions implemented during the pandemic.Copyright © 2023

Marginal Artery of Drummond Pseudoaneurysm Masquerading as Fistulous Tract Resulting in Recurrent Lower Gastrointestinal Bleeding

Introduction: The mortality rate of patients hospitalized with a lower gastrointestinal bleed has been reported at 1.1% in the United States from 2005 to 2014. Pseudoaneurysms, typically associated with pancreatitis, have been described in case reports as a rare condition with a small subset presenting as gastrointestinal bleeding. Our study describes a rare case of recurrent lower gastrointestinal bleeding diagnosed as a pseudoaneurysm by endoscopy and angiography. Case Description/Methods: A 38-year-old male presented to our facility from a long-term care facility with hematochezia and blood clots per gastrostomy-jejunostomy. He had recently been hospitalized for severe coronavirus disease 2019 with a complicated hospital course in the intensive care unit including necrotizing pancreatitis with an abdominal drain, multiple secondary infections, tracheostomy, and percutaneous endoscopic gastrostomy-jejunostomy. On previous hospitalization, he was found to have a small pseudoaneurysm of the gastroduodenal artery and received embolization of the gastroduodenal and gastroepiploic arteries at that time. During transport to our hospital, he was noted to have tachycardia, hypotension requiring norepinephrine, and was transfused one unit of red blood cells. Hemoglobin at this time was 7.5 g/dl after transfusion. Esophagogastroduodenoscopy was completed and showed a gastrojejunostomy tube in the expected location but was noted to be tight to the mucosa, which was pale in appearance. Flexible sigmoidoscopy revealed localized areas of edematous and erythematous mucosa with some associated oozing throughout the sigmoid colon. Repeat evaluation was completed one week later due to recurrent hematochezia. Colonoscopy was performed with identification of an apparent fistulous tract in the sigmoid colon located at 35 cm. Computed tomography angiography localized a pseudoaneurysm arising from the marginal artery of Drummond just proximal to its anastomosis with the ascending branch of the left colic artery and was successfully embolized. Discussion(s): Pseudoaneurysms, such as the one described in this case, have been shown to be associated with pancreatitis and can result if a pseudocyst involves adjacent vasculature. Gastrointestinal bleeding is a rare presentation of this condition. However, this case highlights the importance of repeat colonoscopy and angiography in the setting of a lower gastrointestinal bleed of unknown etiology.

Scientific debrief: cirrhosis

Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.

Secondary infections in critically ill patients with COVID-19: effects of intravenous IgM-enriched immunoglobulin therapy

Introduction: Critically ill patients with severe COVID-19 have an increased risk of bacterial and fungal superinfections due to a dysregulated immune response characterized by lymphopenia and low immunoglobulins levels. The intravenous immunoglobulins are involved in pathogen/toxin scavenging and inhibition of inflammatory mediators gene transcription with anti-apoptotic effects on immune system cells. This research aimed to describe the effects of intravenous IgM-enriched immunoglobulins in COVID-19 patients with sepsis due to secondary infections and low IgM levels. Method(s): We performed an observational retrospective study, including patients admitted to our intensive care unit (ICU) between March 2020 and February 2021 with severe COVID-19 and sepsis due to a superinfection (known or suspected) treated with intravenous IgM-enriched immunoglobulins. We collected demographic data and comorbidities. We noted hemodinamic data, antimicrobial and adiuvant therapies, laboratory results at ICU admission (T0), at the beginning (T1) and at the end (T2) of the IgM-enriched immunoglobulins infusion and at ICU discharge (T3). Result(s): In our cohort of 36 patients (Table 1) the prevalence of documented secondary infections was 83%. We observed a significant reduction of leukocytes from T0 to T3 (10.4 [8.3-14.5] x 103/ mmc vs 7.1 [4.8-11.2] x 103/ mmc, p < 0.01) and the SOFA score from T0 to T2 (7 [6-19] vs 5 [3-7], p < 0.01) and from T0 to T3 (7 [6-10] vs 4 [2-9], p < 0.01);from T1 to T2 (7 [6-9] vs 5 [3-7], p < 0.01) and from T1 to T3 (7 [6-9] vs 4 [2-9], p < 0.01). Cardiovascular SOFA showed a statistically significant reduction from T1 to T2 (4 [3-4] vs 0 [0-3], p < 0.01). Conclusion(s): The IgM-enriched immunoglobulins could improve organ function, as evidenced by the reduction of the SOFA score. Although the latest Surviving Sepsis Campaign guidelines suggest against using of IgM-enriched immunoglobulins, our study supports its use as an adjunctive therapy in COVID-19 patients with septic shock.

Synthesis and evaluation of imidazole-bearing chalcones as a potential treatment for pulmonary aspergillosis

Pulmonary aspergillosis (PA) is a category of respiratory illnesses that significantly impacts the lives of immunocompromised individuals. However, new classifications of secondary infections like influenza associated aspergillosis (IAA) and COVID-19 associated pulmonary aspergillosis (CAPA) only exacerbate matters by expanding the demographic beyond the immunocompromised. Meanwhile anti-fungal resistant strains of Aspergillus are causing current treatments to act less effectively. Symptoms can range from mild (difficulty breathing, and expectoration of blood) to severe (multi organ failure, and neurological disease). Millions are affected yearly, and mortality rates range from 20-90% making it imperative to develop novel medicines to curtail this evolving group of diseases. Chalcones and imidazoles are current antifungal pharmacophores used to treat PA. Chalcones are a group of plant-derived flavonoids that have a variety of pharmacological effects, such as, antibacterial, anticancer, antimicrobial, and anti-inflammatory activities. Imidazoles are another class of drug that possess antibacterial, antiprotozoal, and anthelmintic activities. The increase in antifungal resistant Aspergillus and Candida species make it imperative for us to synthesize novel pharmacophores for therapeutic use. Our objective was to synthesize a chalcone and imidazole into a single pharmacophore and to evaluate its effectiveness against three different fungi from the Aspergillus or Candida species. The chalcones were synthesized via the Claisen-Schmidt aldol condensation of 4-(1H-Imizadol-1-yl) benzaldehyde with various substituted acetophenones using aqueous sodium hydroxide in methanol. The anti-fungal activity of the synthesized chalcones were evaluated via a welldiffusion assay against Aspergillus fumigatus, Aspergillus niger, and Candida albicans. The data obtained suggests that chalcone derivatives with electron-withdrawing substituents are moderately effective against Aspergillus and has the potential for further optimization as a treatment for pulmonary aspergillosis. This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medicine Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Risk factors for severe COVID-19 in a vaccinated population

Introduction/Aim: The risk factors for the development of severe COVID-19 illness have been well researched and documented since the beginning of the pandemic. Subsequently, mass vaccination rollouts have occurred with over 90% of the population being fully vaccinated. The aim of this single centre study was to describe the risk factors associated with the development of severe COVID-19 disease in the vaccinated population. Method(s): A retrospective analysis of all patients admitted to the Gold Coast University Hospital during a week (8 th to 14 th inclusive) in January 2022 was conducted. All patients were included regardless of primary indication for admission. Data was obtained using the electronic medical records and included patient demographics, comorbidities, vaccination status (with fully vaccinated defined as two or more doses of any COVID-19 vaccination), COVID-19 severity (as defined by the National COVID-19 Clinical Evidence Taskforce), complications of disease (such as secondary infection, pulmonary embolism, non-invasive and invasive ventilation, length of stay, ICU admission, mortality, representation/readmission). Univariate analysis was then performed. Result(s): 162 patients were admitted to the Gold Coast University Hospital during the study period and included in the analysis. 103 (63%) patients were fully vaccinated. 52 (32%) patients developed severe COVID-19 disease. In the fully vaccinated group, 34 (33%) patients developed severe COVID-19, compared with 18 (32%) in unvaccinated group). Chronic cardiovascular disease (p=<0.001), respiratory disease (p = 0.025), renal failure (p = 0.044), diabetes (p = 0.003) and current immunocompromise (p = 0.025) were associated with the development of severe COVID-19. Obesity was not a significant risk factor. Conclusion(s): Risk factors for progression to severe COVID 19 previously identified in unvaccinated patients early in the pandemic (with the exception of obesity) remain significantly associated with risk of severe disease in the vaccinated population.

Value of Biofire Filmarray pneumonia panel in evaluating secondary infection in critically ill patients with Coronavirus disease 2019.

Objective To explore the application value of Biofire Filmarry pneumonia panel (PN) in detection of secondary and concomitant pathogen among critically ill patients with coronavirus disease 2019(COVID-19). Methods We consecutively included and analyzed the clinical data of critically ill patients with COVID-19 transferred to the ICU from February to April 2020 in the Sino-French Campus of Wuhan Tongji Hospital. Samples of Bronchoalveolar lavage fluid obtained by bedside bronchoscopy were sent for Biofire Filmarray PN and standard culture concomitantly. We compared the results of two methods and evaluated their concordance. Results In total, 21 critically ill patients with COVID-19 were included and 54 samples were tested, including 33 (61.1%) Biofire Filmarray PN tests (21 patients) and 21 (38.9%) standard cultures (14 patients), in which 19 pairs (38 samples) underwent both tests simultaneously. In Biofire Filmarray PN group, the turnaround time was about 1 hour. There were 74 positive results in 32 samples (97.0%) from 20 patients, including 29 cases(39.2%) of Acinetobacter baumannii complex, 21 cases (28.4%) of Pseudomonas aeruginosa, 16 cases (21.6%)of Klebsiella pneumoniae, 5 cases (6.8%) of Escherichia coli, 1 case (1.4%)each of Enterobacter cloacae, Haemophilus influenzae, and respiratory syncytial virus. In the standard culture group, the turnaround time was about 3 days. 19 positive results returned in 16 (76.2%) samples from 11 patients, including 8 cases (42.1%) of Pseudomonas aeruginosa, 6 cases (31.6%) of Acinetobacter baumannii, 4 cases (21.1%) of Stenotrophomonas malt and 1 case (5.3%) of Myxobacterium. Among the 19 pairs of "back-to-back" specimens, 15 pairs were concordant, and the agreement ratio was 78.9%. Conclusions Acinetobacter baumannii and Pseudomonas aeruginosa may be the common pathogens of secondary or concomitant infection in critically ill patients with COVID-19. Biofire Filmarray PN is a rapid diagnostic test and has application value in such patients;its sensitivity and accuracy require further investigation with larger sample sizes.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Consensus of Chinese experts on protection of skin and mucous membrane barrier for health professions fighting against coronavirus disease 2019.

Health professions preventing and controlling coronavirus disease 2019 are prone to skin and mucous membrane injuries, which may cause acute and chronic dermatitis, secondary infections and aggravation of underlying skin diseases. This is a consensus of Chinese experts on measures and advice on hand cleaning- and medical glove-related hand protection, mask-and goggles-related face protection, ultraviolet-related protection, as well as eye, nasal and oral mucosa, outer ear and hair protection. It is necessary to strictly follow standards on wearing protective equipment and specifications on sterilizing and cleaning. Both insufficient and excessive protection will adversely affect the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.Copyright © 2020 by the Chinese Medical Association.

Corynebacterium amycolatum infective endocarditis in a patient with severe COVID-19: a case report.

Objective. To present a case of successful treatment of a secondary bacterial infection caused by non-diphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance. Materials and methods. A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses;previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient's history of beta-lactam intolerance. Results. A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection. Conclusions. Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Procalcitonin Values Fail to Track the Presence of Secondary Bacterial Infections in COVID-19 ICU Patients.

The development of secondary bacterial infections in COVID-19 patients has been associated with increased mortality and worse clinical outcomes. Consequently, many patients have received empirical antibiotic therapies with the potential to further exacerbate an ongoing antimicrobial resistance crisis. The pandemic has seen a rise in the use of procalcitonin testing to guide antimicrobial prescribing, although its value remains elusive. This single-centre retrospective study sought to analyse the efficacy of procalcitonin in identifying secondary infections in COVID-19 patients and evaluate the proportion of patients prescribed antibiotics to those with confirmed secondary infection. Inclusion criteria comprised patients admitted to the Grange University Hospital intensive care unit with SARS-CoV-2 infection throughout the second and third waves of the pandemic. Data collected included daily inflammatory biomarkers, antimicrobial prescriptions, and microbiologically proven secondary infections. There was no statistically significant difference between PCT, WBC, or CRP values in those with an infection versus those without. A total of 57.02% of patients had a confirmed secondary infection, with 80.2% prescribed antibiotics in Wave 2, compared to 44.07% with confirmed infection and 52.1% prescribed antibiotics in Wave 3. In conclusion, procalcitonin values failed to indicate the emergence of critical care-acquired infection in COVID-19 patients.

Meta-analysis of SARS-CoV-2 reinfection rate in the world.

Objective We aimed to review the data available to explore prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the real world. Methods We searched observational cohort studies and case-control studies that described the SARS-CoV-2 reinfections in PubMed, Embase, Web of Science, CNKI and WanFang Data from inception to 11 Dec 2022. Studies, data extracted and quality assessed were selected according to strict inclusion exclusion criteria. All analyses were using Stata version 16.0. Results A total of 24 studies were included, involving 78 635 cases of SARS-CoV-2 reinfection and 6 616 869 cases of SARS-CoV-2 primary infection. In cases after the primary SARS-CoV-2 infection, the pooled prevalence of reinfection was 2.06% (95% CI: 1.73% - 2.40%). Compared with other age groups, the secondary infection rate was higher in those aged 40 - < 50 years 2.97% (95% CI: -1. 20%-7 14%) and 50-<60 years 2. 32% (95% CI: -0.74%-5.38%). In vaccination status group, the pooled prevalence was 5.47% (95% CI: 1.99%-8.95%) in unvaccinated cases, 1.85% (95% CI: 1.63%-2.08%) for those received partial COVID-19 vaccination, and 1.11% (95% CI: 0.34%-1.89%) for those received fully vaccination. In addition, the pooled prevalence of SARS-CoV-2 reinfection was 6.02% (95% CI: 5.67%-6. 37%) in the health care workers. Conclusions There is a risk of SARS-CoV-2 reinfection, but the results of this global real-world meta-analysis showed that the rate of reinfection is not high. It is recommended to scientifically understand the risk of SARS-CoV-2 reinfection, strengthen public health education, maintain healthy habits, and reduce the risk of SARS-CoV-2 reinfection.Copyright © 2023, Publication Centre of Anhui Medical University. All rights reserved.

X-Linked Inhibitor of Apoptosis (XIAP) deficiency presenting as hemophagocytic lymphohistiocytosis triggered by drug allergy

X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency associated with recurrent hemophagocytic lymphohistiocytosis (HLH) episodes. The clinical phenotypes of XIAP deficiency vary, ranging from splenomegaly to life-threatening inflammation. We report a case of XIAP deficiency with unusual late-onset HLH presentation likely triggered by a drug allergy. A previously healthy adolescent boy presented to the hospital with fever and rash seven days after starting antibiotics for a neck abscess. Laboratory evaluation demonstrated cytopenias, elevated liver enzymes, and increased inflammatory markers. Initially, antibiotics were discontinued due to concern for drug rash. He continued to deteriorate clinically and became hypotensive. Additional testing revealed decreased NK cell function, as well as elevated ferritin, triglycerides, and soluble IL-2 receptor. SLAM-Associated Protein (SAP) and XIAP evaluation by flow cytometry demonstrated decreased XIAP expression. Subsequently, genetic testing revealed a known pathogenic mutation in BIRC4 (c.421_422del), confirming the diagnosis of XIAP deficiency.Copyright © 2023

Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Vali-dation and Current Progress in Trials

Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.

Antimicrobial Resistance: The Potent Enemy Lurking Behind COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic due to its high transmissibility and pathogenicity. It is a beta clade zoonotic coron-avirus like severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Though no effective medication has been developed against the deadly COVID-19 disease, henceforth old antimicrobial drugs have been repurposed to treat the COVID-19 patients. In this report, a brief account of the used medication and the potential mechanism of antimicrobial drugs against SARS-CoV-2 has been provided. Based on the earlier in-cidences, the antimicrobials are expected to lose the battle against SARS-CoV-2. The vast lacuna in the research and development of vaccines has led to overuse of the already formulated antimicro-bial drugs, which in turn has led to a distressing problem called "Antimicrobial resistance (AMR)". A complete assay of AMR has been given including its cause, mechanism, spread, and conse-quences. The other two interlinked problems, namely environmental deterioration and secondary in-fections, are elaborated. Moreover, to combat the AMR problem, the way forward has been discussed in detail.Copyright © 2021 Bentham Science Publishers.

Tocilizumab reduces the need for mechanical ventilation in severe Coronavirus Disease 2019 (COVID19), the Greek Experience in a pragmatic clinical setting

Introduction: Severe COVID-19 can result in rapid clinical deterioration consistent with cytokine release syndrome leading to mechanical ventilation. Aim(s): To evaluate clinical outcomes in patients with severe COVID-19 pneumonia who were treated with Tocilizumab in an attempt to hinder their downfall to mechanical ventilation. Material(s) and Method(s): We reviewed consecutive inpatients with severe pneumonia secondary to COVID-19 confirmed by nasopharyngeal polymerase chain reaction (PCR) between March 2021 and December 2021 who presented with >50% lung infiltrates on chect CT scan, WHO score 6-8, pO2/FiO2<200. Result(s): 135 patients received Tocilizumab compared to 160 controls who received standard care. Baseline demographics, comorbidities, inflammatory markers, and corticosteroid treatment were similar between the two groups. Patients who received Tocilizumab had significantly lower intubation rates (6% vs 19%, P = 0.001) than controls and lower 60day mortality (3% versus 8.9%, p=0.02). Age range was similar in the Tocilizumab and control group. Importantly, there were no secondary infections observed in the Tocilizumab group. Conclusion(s): Administration of tocilizumab in carefully selected patients with severe COVID19 pneumonia hindered their downfall to intubation, decreased 60day mortality and improved clinical outcomes.

Association of Vitamin D and Secondary Infection in COVID-19.

Introduction: Vitamin D plays a role in the modulation of cytokine release, inflammation, innate and adaptive immunity. It has been frequently discussed that the hyperinflammatory response that causes acute respiratory distress syndrome or other organ damage due to SARS-CoV-2 at the beginning of the pandemic can be modulated by the adequacy of vitamin D. The relationship of vitamin D with many conditions such as mortality, number of intensive care unit stays, disease severity, and organ damage has been investigated, but the information on its effect on secondary infections that occur during the course of the disease is limited. In this study, it was aimed to reveal the relationship of vitamin D with secondary infections that occur during the course of COVID-19 disease. Material(s) and Method(s): Medical records of patients hospitalized in the COVID-19 pandemic service with the diagnosis of COVID-19 were evaluated retrospectively. Result(s): One hundred eighty-one patients were included in the study. The mean of 25(OH) vitamin D was found to be 18.76 +/- 9.82 ng/mL. When 25-hydroxy vitamin D was compared with gender, disease severity, mortality, need for mechanical ventilation and presence of symptoms, no statistically significant difference was found (p> 0.05). The medical data of the patients during their hospitalization were analyzed and secondary infection was detected in 14.9% (n= 27). When 25-hydroxy vitamin D and the presence of secondary infection were compared, the 25(OH)D vitamin level of those with secondary infection was found to be low and this was found to be statistically significant (p= 0.016). As a result of the evaluation made by ROC analysis, 25-hydroxy vitamin D was found to have a diagnostic value in predicting positive culture results in COVID-19 patients (AUC= 0.771, 95% Confidence Interval= 0.612-0.810, p= 0.003, p< 0.05). Conclusion(s): While vitamin D continues to be an important topic of discussion in COVID-19 disease due to its effects on the immune system, it should not be forgotten that low vitamin D increases the risk of secondary infection developing in the course of COVID-19 and this may have an impact on prognosis.Copyright © 2022 Bilimsel Tip Yayinevi. All rights reserved.

Follow up outcome in COVID-19 patients with persistent symptoms from central India

Introduction: Secondary infections are a known complication post viral respiratory infections. Secondary infections have always been significant cause of morbidity and mortality in previous well-studied influenza pandemics1. Aims and Objectives: We aimed to diagnose secondary infection early using indicated interventional procedures in post COVID-19 patients with persistent respiratory symptoms more than 4 weeks. Method(s): Post COVID-19 patients with persistent respiratory symptoms who presented to GHRI, Nagpur (India) during 2nd wave were selected for the study. Patients with persistent respiratory symptoms more than 4 weeks after recovering from COVID-19 infection and Radiological abnormality on either Chest X-ray or HRCT Chest were subjected to bronchoscopy or medical thoracoscopy as indicated. Result(s): A total of 72 patients with available culture reports were assessed. Persistent cough, fever and shortness of breath were present in 52.8%, 19.4% and 11.1% of patients respectively. We found evidence of respiratory infections in total 30.5% patients. 11.1% were found to be suffering from pulmonary (3 were drug resistant) and 2.8% from pleural tuberculosis. Also, 4.2% patients were found to be suffering from fungal and 12.5% patients from Bacterial and 6.9% of patients were found to be suffering from more than one infection. Conclusion(s): Meticulous follow up with indicated interventional procedures is useful and safe in diagnosing pulmonary infections early in post COVID-19 patients.