Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 22, Issue 7, 2022

More than 200 viruses infect humans, but treatments are available for less than ten of them. To narrow the gap between ‘bugs and drugs,’ a paradigm shift is required. The “one drug, one bug” approach can be expanded to a “one drug, multiple bugs” strategy such that the host’s defense system is targeted rather than the virus. Viral superinfection therapy (SIT) activates interferon genes’ natural, antiviral defense system of host cells following exposure to viral infection, e.g., superinfection with an attenuated infectious bursal disease virus (IBDV) with the release of its double-stranded RNA (dsRNA) cargo inside host cells. An attenuated IBDV therapeutic vaccine has successfully treated hepatitis A virus infection (HAV) in marmoset monkeys as well as acute hepatitis B and hepatitis C virus infections (HBV/HCV) in 42 patients. SIT has also been shown to be safe and effective in four patients with chronic HBV or HCV infection with hepatic decompensation. The proof-of-principle of SIT has also been demonstrated in a 43-year-old male patient with COVID-19. Three doses of orally administered IBDV (3x10⁶ IU) alleviated most of his COVID-19 symptoms; even his sense of smell returned within a week. Two additional COVID-19 patients responded similarly to oral treatment with IBDV. Furthermore, a severe herpes zoster ophthalmicus outbreak with orbital edema responded to a combination of acyclovir and 7 doses of IBDV (7x10⁶ IU) within a few days. IBDV is simple to manufacture and affordable, even in resource-limited settings. Acid-resistant IBDV can be orally administered in an outpatient setting, providing simple dosing and high medication adherence. Under an Emergency Use Authorization, the broad-spectrum IBDV drug candidate could be tested immediately in clinical trials and rapidly distributed to millions of early-stage patients with COVID-19. The German Paul Ehrlich Institute is currently supporting a phase I safety study for persons acutely infected with SARS128;‘CoV-2. An expert team of the US National Institutes of Health-sponsored ACTIV public-private partnership came to the conclusion that the IBDV drug candidate shows merit as a potential treatment for COVID19, and an FDA-approved clinical trial is in the pipelines in Los Angeles.

Since the advent of the COVID-19 pandemic in 2019, a mammoth research activity targeting the etiological features of COVID-19 has commenced. Many aspects of the disease have been studied, and various others are under consideration. The secondary microbial coinfections with COVID-19 have generated some serious concerns across the globe. This review mainly focuses on the notable secondary coinfections. The coinfection of influenza, tuberculosis, and typhoid may mimic the original COVID-19 symptoms. Physicians and clinicians must focus on the secondary coinfections which may aggravate the disease progression towards acute respiratory disorder syndrome (ARDS). Diagnostic strategies must also be redefined to determine the actual underlying secondary coinfection. There is a need for combination therapy and diagnostic approaches to minimize the risks associated with the COVID-19 pandemic effectively.

Over two years after the start of the SARS-CoV-2 epidemic, which has demised over 5 million people, the world is still on high COVID-19 alert in February 2022, and new variants are emerging. Since January 2020, the World Health Organization (WHO) has been closely monitoring and analyzing the evolution of SARS-CoV-2 in partnership with national authorities, public health organizations, and scientists. To prioritize global monitoring and research and to guide the continuing global response to the COVID-19 pandemic, distinct SARS-CoV-2 variants were labelled as Variant of Interest (VOI) and Variant of Concern (VOC). The World Health Organization and its international sequencing networks are constantly monitoring SARS-CoV-2 mutations and informing countries about any adjustments that may be required to respond to the variant and, where possible, prevent its spread. Since January 2021, multiple viral variations have evolved and grown dominant in numerous countries, with the Alpha, Beta, Gamma, and Delta varieties being the most prevalent too far. On November 20, 2021, Omicron was born into a COVID-19-weary world, replete with rage and resentment at the pandemic's broad detrimental effects on social, emotional, and economic well-being. Although earlier VOCs originated in a world where natural immunity to COVID-19 infections was widespread, the fifth VOC, Omicron, has emerged in an environment where vaccine immunity is rising.

Epigenetics is related to the various pathways that show long128;term impacts on the gene expression patterns without alterations in nucleotide sequences. Over the last decade, epigenetics advanced significantly in the science of biology, oncology, innate immunity as well as pathogens and infectious diseases. In the present paper, we aimed to review the relationships between COVID-19 and epigenetic alterations of the infected cells. Coronavirus is one of the known infectious diseases that causes respiratory infection, such as pneumonia and coughing, while in animals, it causes diarrhea and upper respiratory disorders. This virus could be transmitted human to human or human to an animal through droplets. It translocates via membrane ACE-2 exopeptidase into the host cells. In conclusion, hypomethylation of angiotensin II converting enzyme (ACE II) possibly upregulates its expression, enhancing the possibility of SARS-CoV-2 infection.

Backgrounds: SARS-CoV-2 infection typically presents with fever and respiratory symptoms. Besides this, COVID-19-related central and peripheral nervous system manifestations are emerging. Objectives: This study summarises the demographics, clinical profiles, laboratory findings, management strategies, and outcomes in a large number of patients with COVID-19-related GBS and its variants. We also compared its clinical profile with Zika and dengue virus-related GBS. Methods: The authors carried out a literature search up to Dec 31, 2020, in MEDLINE, PubMed, SCOPUS, Cochrane database, and Google Scholar for all published articles. Results: The study identified 54 different types of articles consisting of 70 cases from 17 countries worldwide. A maximum of 15 cases (21.4 %) were identified from Italy, followed by the USA (12; 17.1 %), Spain (11; 15.7 %), and Iran (10; 14.3 %). The age group that was more than 60 years had the most cases, i.e., 32 (45.7 %), followed by the age group 40-60 with 25 cases (35.7 %) with a male to female ratio of 2. Maximum cases were treated with IVIG infusion 58 (82.9 %), followed by Plasma exchange 13 (18.6 %) cases. Out of 70 cases, 7 (10 %) cases were manifested as Miller-Fisher syndrome. The most predominant electrodiagnostic variant was demyelinating neuropathy in 41 (73.21 %) cases. The outcome reported in 67 cases was survival in 63 (90 %) cases and death in 4 (5.7 %) cases. Conclusion: Covid-19-related GBS were reported worldwide with a better outcome. Both postinfectious and parainfectious patterns were reported. Early recognition with prompt management of GBS can prevent further severe morbidity and mortality.

Backgrounds & Aim: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus. Knowledge of the fate of infection and risk factors among health care workers is essential to enforce special infection control measures. We aimed to determine the percentage of COVID-19 infection and the associated risk factors as well as the predictors of COVID- 19 among health care workers in Assiut University Hospital. Methods: A cross-sectional study was performed that included one hundred health care workers that were confirmed by PCR to be COVID-19 cases admitted to Assiut University Hospital over six months between May 2020 and November 2020. All participants were subjected to thorough history taking and full clinical examination as well as investigations. Results: Out of the 100 HCWs enrolled in the study, 52% were males, 26% were obese, 68% were doctors, and 38% were from the medical department. Fourteen percent of healthcare workers were admitted to ICU, of which 93% were cured. The predictors for severity of cases were as follows: being a doctor OR (6.804) P=0.037, old age OR (1.179) P=0.000, and hospital stay OR (0.838) P=0.015. Conclusion: Health care workers are at risk for severe COVID-19 infection. Being a doctor, old age, and duration of hospitalization were the predictors for the severity of cases of health care workers.

Background: Fourier Transform Infrared (FTIR) spectroscopy and reverse phase highperformance liquid chromatography, RP-HPLC analysis have been used for the quantitative determination of local l commercially available Pitavastatin products. Methods: The FTIR method of analysis is not widely used in pharmaceutical quality control laboratories. This technique is non-destructive, reliable, precise, and efficient, and the samples can be prepared easily. These features emphasized that the FTIR technique can be considered as a potential analytical method for quantitative analysis in pharmaceutical laboratories. Results: It is strongly recommended that FTIR analytical method can be applied simultaneously with RP-HPLC techniques for quality control purposes of drug analysis. Both methods of analysis have shown comparable precision and good repeatability and reproducibility for analysis of Pitavastatin which can be generalized for other pharmaceutical products. Conclusion: In addition, FTIR is not only used for the determination of vibrational modes and structure in the fingerprint region, but it can be also generally applied in quantitative analysis for many pharmaceutical products.

Background: The presence of the class I integron gene is associated with the emergence of multiple drug resistance (MDR) phenotype in Pseudomonas aeruginosa (P. aeruginosa) isolates. Aim: The objectives of this research were to study the prevalence of integrase genes I (Intel I) and integrase genes II (Intel II) in clinical isolates of P. aeruginosa and its association with antibiotic resistance in these isolates. Methods: The study was a retrograde cross-sectional study that was carried out on 150 clinical isolates of P. aeruginosa isolated from patients with healthcare-associated infections. The isolates were subjected to biochemical identification and antibiotic sensitivity study by discs diffusion test. Intel I & Intel II genes were detected by polymerase chain reaction (PCR). Results: Intel I gene was present in 48% of the isolates, and Intel II was present in 1.3% of the isolates. Intel I gene was detected at a statistically significant high rate in MDR- P. aeruginosa (76.9%, P=0.001) compared to non-MDR- P. aeruginosa (3.4%), while intel II had a statistically insignificant increase in MDR- P. aeruginosa (1.1%, P=1.00) compared to non-MDR-P. aeruginosa (1.7%). Both Intl I/Intl II genes were detected in 2.2% of MDR-P. aeruginosa isolates and were absent in non- MDR-P. aeruginosa isolates with statistically insignificant difference (P=1.00). P. aeruginosa isolates with Intel I gene had an increase in antibiotic resistance pattern to the used antibiotics discs. However, this increase had statistically significant rates only for gentamicin (63.9%, P≤0.001), meropenem (47.2%, P=0.009), trimethoprim/sulfamethoxazole (37.5%, P=0.013) and imipenem (44.4%, P=0.025). Conclusion: The present study highlights the high prevalence of the Intel I gene in clinical isolates of P. aeruginosa, while the Intel II gene was less prevalent in these isolates. There was a significant association between the prevalence of the Intel I gene and the MDR phenotype of P. aeruginosa and resistance to gentamicin, meropenem, trimethoprim/sulfamethoxazole, and imipenem. These findings need future evaluation in a higher number of clinical isolates of P. aeruginosa.

Background: In immuno-compromised organ transplant recipients, toxoplasmosis can be caused by either an infected graft or a latent infection, during which transformation from a chronic state to an active infection (reactivation) is observed. PCR is an accurate and sensitive molecular method widely used in medical sciences, especially in diagnostic procedures. Objective: The aim of this study was to determine the prevalence of early toxoplasmosis infection in bone marrow transplant patients by PCR. Methods: The blood samples of 50 patients with hematological disorders who had received bone marrow transplants were collected using a standard phlebotomy technique. To evaluate antitoxoplasma antibodies, we utilized the enzyme-linked immunosorbent assay (ELISA) method using a specific commercial kit (Akon) based on the manufacturer’s instructions. Genomic DNA extracted from toxoplasma tachyzoite was used as the template for PCR. Results: 22 (44%) patients were women, and 28 (56%) were men. There were no significant differences in the distribution of genders and age groups in patients with various cancers. Antitoxoplasma IgG was positive in 39 patients, while none of them were IgM positive. According to PCR results, 5 patients were positive for toxoplasmosis. All of the PCR-positive cases (2 with AML, 2 with HL, and 1 with AA) had successful engraftment at 40 days post-transplantation. Conclusion: Because of the higher efficacy of PCR in the diagnosis of toxoplasmosis, using this method along with other routine diagnostic modalities in this condition is recommended. PCR-based techniques can also be utilized to periodically determine parasite load in blood after transplantation.

Mucormycosis, also known as "black fungus," is a potentially fatal disorder that causes blurred or double vision, chest pain, and breathing problems. The introduction of novel risk factors and causative agents, as well as the problems with controlling the disease, are all significant problems with mucormycosis in India. It is most common among COVID-19 patients. Mucormycosis is an invasive fungal disease that primarily affects immunosuppressant patients, mainly caused by mold fungi of the genus mucor, rhizopus, rhizomucor, and absidia, which are in the zygomycetes class and the Mucorales order. The most common risk factor is diabetes mellitus, followed by haematological malignancy and solid-organ transplantation. Reversal of underlying predisposing factors, surgical debridement of infected tissues, and proper antifungal therapy are all required for the treatment of mucormycosis. In this review, the epidemiology, pathogenesis, and symptoms of black fungus and its association with covid-19, treatment, and diagnosis are discussed.

Superantigens (Sags) are a part of some viral or bacterial proteins that stimulate T cells and antigen-presenting cells leading to systemic immune repose and inflammation. SAgs might have a possible role in various inflammatory childhood diseases (e.g., Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis). Worldwide studies have been conducted to determine the role of staphylococcal SAgs (TSST-1) in various inflammatory diseases. The SAgs (TSST-1) not only induce sepsis and septic shock (even in negative blood culture for S. aureus), but may also have a significant role in various childhood inflammatory diseases (e.g., KD, OMS, Polyp, dermatitis, psoriasis). In proven Sags-induced inflammatory diseases, the inhibition of the cell-destructive process by SAgs suppressants might be helpful. In toxic shock or sepsis-like presentation and even in cases with negative blood cultures, immediate use of anti staphylococcal drugs is required. Occasionally, the clinical presentation of some human viruses (e.g., coronavirus and adenovirus) mimics KD. In addition, coinfection with adenovirus, coronavirus, and para-influenza virus type 3 has also been observed with KD. It has been observed that in developed KD, bacterial sags induced an increase in acute-phase reactants and in the number of white blood cells, and neutrophil counts. Multisystem inflammatory syndrome in children (MISC) and KS were observed during the recent COVID-19 pandemic. This study summarized the relationship between viral and bacterial SAgs and childhood inflammatory diseases.

SARS-CoV-2 was reported as the cause of coronavirus disease 2019 (COVID-19) in late December 2019. According to sequencing and phylogenetic studies, the new virus belongs to Coronaviridae family and Betacoronavirus genus. Genomic sequence analysis has shown SARS-CoV-2 to be similar to SARS. SARS-CoV-2 is more infectious, and the high level of COVID-19 community transmission has led to a growing pandemic. Although infections in most patients with COVID-19 are moderate or mild, 20% of the patients develop a severe or critical form of the disease. COVID-19 may affect a wide range of organs and tissues, including the respiratory system, digestive system, nervous system, and skin. Patients with COVID-19 have been confirmed to have renal, cardiovascular, gastrointestinal, and nervous system problems in addition to pulmonary involvement. The pathogenesis of SARS-CoV-2 is being investigated, but it is possible that the organ damage might in part be caused by direct viral damage (detection of inclusion bodies in tissues, such as the kidneys), dysregulation of the immune system, renin-angiotensin system, bradykinin pathway, and coagulation, as well as host genetic factors and their polymorphisms, which may affect the disease severity. In this review, an update on the possible pathogenesis pathways of COVID-19 has been provided. It is hoped that the best care strategy will be developed for patients with COVID-19 by identifying its pathogenesis pathways.