Burden of respiratory coinfections in haematology patients with COVID-19

Introduction: Following the lifting of generalised restrictions and universal masking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2)- infected patients, especially the clinically extremely vulnerable (CEV) haematology patients, are at an increased risk for other respiratory viral coinfections;therefore, physicians need to be cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV- 2 and other respiratory pathogens in patients with haematological cancers presenting to a large tertiary care hospital. Method(s): From July 2022-December 2022, patients with haematological disorders were screened for SARS-CoV- 2 and other 10 common respiratory pathogens by PCR. We performed a retrospective analysis of patients with concurrent respiratory viruses and will prospectively evaluate the same from Jan 2023 to March 2023. Result(s): During this period a total of 322 inpatients had routine screening and additional 6213 swabs were done in the outpatient/ambulatory setting, of which 294 were positive in 221 patients. We excluded all patients who had a single positive PCR swab result and specifically analysed only patients with coinfections. We identified 30 patients (14%) who had respiratory coinfections with 73 viral infections/reactivations over 6 months period, which represented 25% of all positive swabs: 25 inpatients (19 symptomatic/6 asymptomatic) and 48 in outpatients (32 symptomatic/16 asymptomatic). The median age of the cohort was 47.3 years (21-77). Patients were post allograft (n = 15), autograft (n = 7), post CART (n = 5) and postchemotherapy (n = 4). Of the 30 cases, 13 patients had concurrent infections: 5 SARS-CoV2, 10 Respiratory syncytial virus (RSV), 7 Rhino and 4 Influenza A, with all patients having dual viral infection. The remaining 17 patients had multiple viral infections but separated by a median of 54 days (range 27-137 days): 16 SARS-CoV2, 5 RSV, 6 Rhino, 2 Parainfluenza, 2 Adeno and one each of Influenza A, Influenza B, and metapneumovirus. Of the treatable infections (n = 46), 22% were detected on routine asymptomatic swabbing, with 50% of SARS-CoV2 detected on routine swabs. All 8 patients with Influenza were treated with oseltamivir, of 16 RSV cases one was treated with oral ribavirin and of the 22 SARS-CoV2 patients, 5 were treated (4 Paxlovid and 1 Remdesivir). No patients needed intensive care support and no deaths were reported. Conclusion(s): The burden of respiratory coinfections in CEV cohort has a significant impact on respiratory isolation and management, including appropriate & timely initiation of therapy for treatable viral infections. Although mortality was not increased secondary to respiratory coinfections and none needed intensive care, larger prospective cohorts are needed to assess the exact impact.

Respiratory syncytial virus: desperately seeking solutions

Respiratory syncytial virus (RSV) infection remains a major public health problem, especially in younger children and the elderly. But several monoclonal antibodies, antivirals and vaccines, either recently launched or in development, offer new hope for RSV prevention and treatment.Copyright © 2023 Wiley Interface Ltd.

A selectivity-enhanced colloidal crystal array for ribavirin sensing based on the synergistic effect of covalent and non-covalent interactions

Ribavirin is an important antiviral with demonstrated activity against coronaviruses such as severe acute respiratory syndrome coronavirus and coronavirus disease 2019 virus. However, abuse of ribavirin will cause great environmental damage and threaten human health owing to its reproductive toxicity and teratogenicity. Therefore, an innovative detection method is demanded for simple and sensitive detection of ribavirin. This work reports an imprinted colloidal crystal array (ICCA) for ribavirin sensing. The building blocks of the ICCA are ribavirin imprinted spheres, which possess superior binding efficiency toward ribavirin. Benefiting from the highly ordered structure, the ICCA exhibits optical properties which change upon binding ribavirin. The changes in reflectance wavelength enable a fast and label-free detection of ribavirin between 21 and 245 μmol L−1. Moreover, the sensor shows excellent selectivity for ribavirin detection in river water. Overall, all the results reported in this work demonstrate that the ICCA should be a promising detection tool for antivirals. © 2023 Society of Industrial Chemistry. © 2023 Society of Industrial Chemistry.

The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients.

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.

Audiovestibular and vaccination complications of COVID-19

Objectives: Since its first appearance in Wuhan December 2019, SARS-CoV2 virus received great attention due to its severe symptoms and high spread causing COVID-19 disease which spread all over the world like a pandemic. The causative virus is capable of human-to-human transmission via droplet and direct contact suggesting that upper respiratory tract is the main site to virus manifestations. There is a great diversity in its clinical picture, although the severe respiratory and neurological symptoms are commonly present;however, other symptoms are present. Although otological manifestations are reported in many COVID-19 patients even in asymptomatic cases, they did not receive much attention compared with other critical manifestations. In this article, we paid our attention specifically to the otological manifestations of COVID-19 and their relevance either to the virus infection, treatment, or vaccination through literature review. Conclusion(s): COVID-19 disease has a deleterious effect on the inner ear. This effect is not only due to SARS-Cov-2 infection, but it could be also due to the ototoxic drugs used for treatment. The COVID-19 vaccinations are found to be implicated in the otological symptoms in some cases.Copyright © 2022, The Author(s).

Experimental and Clinical Evaluation of Mefloquine Effectiveness against the Infection Caused by Sars-Cov-2

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

On Analysis of Temperature Based Topological Indices of Some Covid-19 Drugs

A variety of graphical invariants have been described and tested, offering lots of applications in the fields of nanochemistry, computational networks and in different scientific research areas. One commonly studied group of invariants is the topological index, which allows to research the chemical, biological, and physical properties of a chemical structure. Topological indexes are numerical quantities that can be used to describe the properties of the molecular graph. In this article, we draw from the analytically closed formulas of certain molecular structures of coronavirus such as Ribavirin, Sofosbuvir and Oseltamivir by calculating temperature based topological indices.

Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study

Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material(s) and Method(s): A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Result(s): In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Conclusion(s): Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.Copyright © 2023 Oner E et al.

Lassa Fever. Part 2. Laboratory Diagnostics, Treatment, Development of Medications

Globalization and high-speed means of transportation contribute to the spread of infections dangerous to humans. Airborne pathogens have pandemic potential as currently shown in case of the novel coronavirus SARS-CoV-2. Natural focal Lassa fever (LF) common in West African countries, in 35 cases was registered in non-endemic geographical areas because any person infected with Lassa virus (LASV) is a long-term source of infection (up to two months). Cases of person-to-person infection in endemic territories are described. In Germany, the facts of secondary virus transmission from patients to doctors have been recorded during the examination and blood collection from an apparently healthy person as well as during the autopsy of a deceased subjects due to severe LF course. Nonspecific malaise symptoms in LF are also characteristic of numerous other diseases common on the African continent, e.g., malaria and typhoid fever or viral infections such as yellow fever, Chikungunya, dengue and Zika, monkey pox and Ebola virus disease. In this regard, there may be similar dermatological manifestations. Timely detection of cases and differential diagnosis are crucial to ensure safe patient care and use of affordable antiviral therapy for LL provided by the drug Ribavirin. Research methods for studying LASV use polymerase chain reaction (PCR) for detecting viral RNA, electron microscopy, isolation of infectious virus cultured sensitive cells, indirect immunofluorescence reaction, enzyme immunoassay (ELISA) and immuno-chromatographic assays for the detection of antibodies and/or antigen as well as immunoblotting. Currently, test kits based on molecular and genetic methods are mainly used for LF laboratory diagnostics. Since the 1980s, ribavirin has been used to treat patients with LF. The serum accumulation of the drug in large quantities causes hemolysis, development of anemia and impaired renal function. In this regard, treatment options are being considered with decline in its concentration due to combined use with other antiviral drugs. A search for new therapeutic agents capable of inhibiting viral replication at disease early stage has been in progress due to lack of any approved vaccines.

Studying The Effectiveness of Ribavirin in The Experimental Form of Severe Acute Respiratory Syndrome.

The effectiveness of Ribavirin was evaluated by the certainty of disease severity reduction and the coefficient of therapeutic action of drugs at the peak of the pathological process calculated by the following indicators: accumulation of the virus in the lungs, lung damage degree reduction, reduction observed in the severity of changes in the quantitative and qualitative characteristics of white blood, as well as the severity of changes in biochemical blood parameters. Ribavirin is most effective when used according to the emergency prevention regimen at a dose of 20 mg/kg (therapeutic action coefficient - 70%);at a dose of 40 mg/kg according to the therapeutic and prophylactic regimen (therapeutic action coefficient - 60%). Increasing the dose of Ribavirin did not contribute to the therapeutic effectiveness of the drug.Copyright © 2020 Media Sphera Publishing Group. All rights reserved.

A comprehensive review of therapeutic options for COVID-19

Introduction: COVID-19 is a disease that is induced by severe acute respiratory syndrome coronavirus (SARS). Its viral infection is spread swiftly around the world and causes many restrictions, health problems, and expensive treatment costs worldwide. Due to its high prevalence and mortality rate, there is a global challenge to find an effective therapeutic protocol for the prevention and treatment of COVID-19. No one could disclaim the immediate need for a standardized protocol for COVID-19 treatment. Methods: Aiming to prepare a comprehensive review of introducing appropriate remedial options for COVID-19, a wide range of investigation on relevant articles established in the English language published through different publications such as PubMed, Medline, Embase, Science Direct, Scopus, and COVID-Evidence . all researchers and clinicians should try to make more precise knowledge about the viral behavior and treatment of COVID-19 to find an effective vaccine to prevent and treatment of this virus. The main objective of the present study is to review and investigate the available evidence for achieving a more precise preventive and treatment protocol to deal with COVID-19. Findings: many available drugs have been reviewed that include Azithromycin, Lopinavir/ritonavir (LPV/r), Remdesivir, Corticosteroids, Chloroquine, Hydroxychloroquine, Hydroxychloroquine sulfate, Immunoglobulin, Ivermectin, Ribavirin, Favipiravir, Interferon. On the other hand, it is recommended to conduct precise clinical trials on current antimicrobial and antiviral agents that are administered for a long time to find an expeditious and effective response to the COVID-19 pandemic. Although disappointing, it should be noted that there is no effective drug regimen or vaccine against the novel coronavirus. In this regard, using other available antiviral drugs for the treatment of COVID-19 may be effective to some extent. In this study, by investigating some available antimicrobial medicines that may diminish COVID-19 infection, we are trying to introduce a general protocol for controlling this disease.

Safety application of novel coronavirus pneumonia antiviral drugs.

Three antiviral drugs, including interferon alpha (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People's Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug-remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.Copyright © 2020 by the Chinese Medical Association.

Rashes caused by arbidol in a patient with novel coronavirus pneumonia.

A 50-year-old male patient with agitated depression and hyperlipemia received oral amoxicillin and clavulanate potassium 0.5 g once daily and 2 lopinavir and ritonavir tablets twice daily for novel coronavirus infection, based on previous drugs including quetiapine, clonazepam, and atorvastatin calcium. After 3 days, lopinavir and ritonavir was changed to oral arbidol 200 mg, thrice daily due to suspicious drug interaction. After taking arbidol for 3 days, the patient developed red papules on the whole body. Considering that it might be related to amoxicillin and clavulanate potassium, the drug was stopped and loratadine was given. But the rashes were aggravated. Considering that the drug eruption was caused by arbidol, arbidol was discontinued and the rashes subsided in a large area the next day. Then vitamin C injection, calcium gluconate injection, and ribavirin were added. After 5 days, the rashes subsided completely. After 17 days, the patient recovered from pneumonia.Copyright © 2020 by the Chinese Medical Association.

Antiviral agents for COVID-19.

In December 2019, the endemic of COVID-19 broke out in Wuhan, China. The disease is highly contagious and quickly spreads at home and abroad, causing great concern. However, there are no definite effective antiviral drugs in clinical use. Given the urgency of the COVID-19 outbreak, based on the diagnosis and treatment recommendation and relavant researches, this article describes the optional antiviral drugs such as remdesivir, oseltamivir, arbidol, lopinavir/ritonavir, ribavirin, and interferon-alpha to provide a reference for treatment of COVID-19.Copyright © 2020 by the Chinese Medical Association.

Herbal medicines in the treatment of coronavirus disease 2019 (Covid-19)

Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, started in livestock within the markets of Wuhan, China and was consequently spread around the world. The virus has been rapidly spread worldwide due to the outbreak. COVID-19 is the third serious coronavirus outbreak in less than 20 years after Severe Acute Respiratory Syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012. The novel virus has a nucleotide identity closer to that of the SARS coronavirus than that of the MERS coronavirus. Since there is still no vaccine, the main ways to improve personal immunity against this disease are prophylactic care and self-resistance including an increased personal hygiene, a healthy lifestyle, an adequate nutritional intake, a sufficient rest, and wearing medical masks and increasing time spent in well ventilated areas. There is a need for novel antivirals that are highly efficient and economical for the management and control of viral infections when vaccines and standard therapies are absent. Herbal medicines and purified natural products have the potential to offer some measure of resistance as the development of novel antiviral drugs continues. In this review, we evaluated 41 articles related to herbal products which seemed to be effective in the prevention or treatment of COVID-19.Copyright © 2021 The Author(s).

Risk signals mining of ribavirin and interferon-alpha based on the US FDA Adverse Event Reporting System database.

Objective: To identify which induced the symptoms/signs and laboratory abnormal findings occurred in patients with novel coronavirus pneumonia, by disease itself or by ribavirin and interferon-alpha treatments, through mining the adverse events (AEs) signals of the 2 antivirus agents. Method(s): According to the symptoms/signs and laboratory abnormal findings of novel coronavirus pneumonia mentioned in the literature and "Diagnosis and Treatment scheme of Novel Coronavirus Pneumonia (trial version 5)", AEs in this study were selected. Related data were collected from the U.S. FDA Adverse Events Reporting System (FARES) from Jan 1, 2004 to Dec 31, 2019, and the reporting odds ratio (ROR) method was used for signals detection for the above-mentioned 2 drugs. Result(s): A total of 7 582 463 AEs related to drugs were reported in the FAERS database, of which 31 775 related to ribavirin and 2 345 related to interferon-alpha. The results showed that AEs related to ribavirin in respiratory, thoracic, and mediastinal disorders were nasal congestion, cough, laryngeal pain, pharyngeal oedema, productive cough, and dyspnoea;AEs related to interferon-alpha were laryngeal pain and haemoptysis. In other system organ class, AEs related to above 2 drugs were pyrexia, feeling cold, pyrexia, nausea, vomiting, diarrhoea, headache, arthralgia, myalgia, and rash. AEs of laboratory abnormal results related to ribavirin were white blood cell/platelet count decrease and aspartate/alanine aminotransferase increase;AEs related to interferon-alpha were white blood cell/platelet count decrease, aspartate/alanine aminotransferase increase, and lymphocyte count decrease. Conclusion(s): Some AEs induced by ribavirin and interferon-alpha were similar to symptoms/signs and laboratory abnormal findings of novel coronavirus pneumonia, which should be distinguished in the clinical practice.Copyright © 2020 by the Chinese Medical Association.

Acute hemolytic reaction in patients with novel coronavirus pneumonia induced by high-dose ribavirin injection: report of 2 cases.

Two female patients (patient 1, 22-year-old;patient 2, 50-year-old) received IV infusion of ribavirin injection (4 g in the first dose and the next day 1.2 g thrice daily), oral 2 lopinavir and ritonavir tablets twice daily, and aerosol inhalation of recombinant human interferon alpha2b for injection for novel coronavirus pneumonia. There was no obvious abnormality in blood routine and liver function before treatment. Laboratory tests showed red blood cell count (RBC) 2.89x1012/L, hemoglobin (Hb) 75 g/L, alanine aminotransferase (ALT) 22.8 U/L, aspartate aminotransferase (AST) 33.9 U/L, total bilirubin (TBil) 71.2 mumol/L, and indirect bilirubin (IBil) 63.5 mumol/L in patient 1 on the 2nd day of treatment, and RBC 3.46x1012/L, Hb 95 g/L, ALT 17.7 U/L, AST 21.3 U/L, TBil 86.1 mumol/L, and IBil 67.1 mumol/L in patient 2 on the 3rd day of treatment. The direct antiglobulin test was positive, indirect antiglobulin test was negative, and antinuclear antibody test was negative in both patients. They were diagnosed as having acute hemolytic anemia. Con-sidering the relationship to ribavirin, ribavirin was given in reduced dose and then finally discontinued in patient 1, and was discontinued directly in patient 2. On the basis of continued use of the other 2 drugs, both of them were treated with ursodeoxycholic acid. The Hb and bilirubin level of the 2 patients gradually returned to normal.Copyright © 2020 by the Chinese Medical Association.