ORCID Profile
0000-0003-4552-4513
Current Organisation
University of Tasmania
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Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JIPH.2021.11.014
Abstract: Fungal infections have risen exponentially in the last decade. In fact, candidiasis has become the most frequent type of hospital acquired infection especially in patients receiving treatment for chronic and terminal illnesses in a hospital. A retrospective analysis for a period of twenty year was undertaken to analyze the incidence rate of candidiasis, especially of Candida species, patients treated in a tertiary care center. Clinical data was collected from s les of patients who were receiving tertiary care were presenting with clinically suspected fungal infections. Direct microscopy with 10% potassium hydroxide was done to visualize the presence of fungal elements, and Gram staining was done for any suspected yeast infection. The s les were inoculated on Sabouraud's Dextrose Agar and kept at 22 °C. A total of 1256 s les with presumed fungal etiology were included in the study. The maximum number of fungal infections were present in elderly (70-79 years age). Females (53.8%) were more affected (45.5%). 21% isolates were identified as yeast but belonged to non-Candida fungi. Among Candida species, Candida albicans was the most dominant species (58.3%) followed by Candida glabrata (6.4%). The year-round data of fungal cases showed that the highest incident of Candida albicans infection were in January with a mean value of 3.80, while the lowest infections were reported in June, with prevalence of 2.32 of C. albicans. The twenty-year data analysis showed that the years 2001 and 2000 showed the highest incidents of C. albicans, with a mean prevalence of 7.50 and 6.83, respectively. Specimen vs fungal prevalence data showed that 38% of the C. albicans were isolated from body aspirate specimens, followed by 26% from swab specimens. The high prevalence of Candida spp. in the present study suggests increased susceptibility of patients with critical or chronic illnesses to fungal infections.
Publisher: Informa UK Limited
Date: 30-06-2021
Publisher: African Journals Online (AJOL)
Date: 13-07-2018
Publisher: MDPI AG
Date: 07-05-2021
DOI: 10.3390/PATHOGENS10050565
Abstract: The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the erse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the erse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.
Publisher: MDPI AG
Date: 24-09-2022
DOI: 10.3390/PATHOGENS11101092
Abstract: Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by Klebsiella pneumoniae are notorious for being difficult to treat due to resistance to commonly used antimicrobials. Klebsiella pneumoniae isolates from bloodstream infections are becoming increasingly resistant to carbapenems. In the fight against carbapenem-resistant Klebsiella pneumoniae, colistin [polymyxin E] is the antimicrobial of choice and is thus widely used. Objective: This study aimed to determine the global prevalence of colistin resistance amongst Klebsiella pneumoniae isolates from bloodstream infections. Methods: PubMed, Medline, Scopus, and the Cochrane Library were searched for published articles without restricting the search period. Studies meeting the predefined inclusion and exclusion criteria were included, and quality was assessed using Joanna Briggs Institute Checklist. We used a statistical random effect model to analyze data with substantial heterogeneity (I2 50%) in the meta-analysis. Results: A total of 10 studies out of 2873 search results that met the inclusion criteria were included in the final synthesis for this study. A pooled prevalence of colistin resistance was 3.1%, 95% CI (1.5–4.7%). The highest colistin resistance pooled prevalence was recorded in isolates studied in 2020 and beyond 12.90% (4/31), while Klebsiella pneumoniae isolates studied in 2015 and before and in 2016–2019 showed a pooled colistin resistance rate of 2.89% (48/1661) and 2.95% (28/948), respectively. The highest colistin resistance was found in Klebsiella pneumoniae isolates from Thailand (19.2%), while the least pooled resistance was in Klebsiella pneumoniae from South Korea (0.8%). The pooled prevalence of the multidrug-resistant (MDR) of Klebsiella pneumoniae from bloodstream infection ranged from 80.1%, 95% CI (65.0–95.2%), and the resistance prevalence of other antibiotics by Klebsiella pneumoniae from bloodstream infections were as follows ciprofloxacin (45.3%), ertapenem (44.4%), meropenem (36.1%), imipenem (35.2%), gentamicin (33.3%), amikacin (25.4%) and tigecycline (5.1%). Klebsiella pneumoniae recovered from the intensive care unit (ICU) showed higher colistin resistance, 11.5% (9/781%), while non-ICU patients showed 3.03% (80/2604) pooled colistin resistance. Conclusion: This study showed low colistin resistance in Klebsiella pneumoniae isolates from global bloodstream infections. However, significant colistin resistance was observed in isolates collected from 2020 and beyond. Significant colistin resistance was also observed in Klebsiella pneumoniae isolates in bloodstream infections from the intensive care unit (ICU) compared to those from non-ICUs. As a result, there is a need to institute colistin administration stewardship in the ICU in clinical settings.
Publisher: MDPI AG
Date: 06-10-2022
DOI: 10.3390/MICROORGANISMS10101978
Abstract: The epidemiological and clinical aspects of coronavirus disease-2019 (COVID-19) have been subjected to several investigations, but little is known about symptomatic patients with negative SARS-CoV-2 PCR results. The current study investigated patients who presented to the hospital with respiratory symptoms (but negative SARS-CoV-2 RT-PCR results) to determine the prevalence of bacterial pathogens among these patients. A total of 1246 different s les were collected and 453 species of bacterial pathogens were identified by culture. Antibiotic susceptibility testing was performed via the Kirby Bauer disc diffusion test. Patients showed symptoms, such as fever (100%), cough (83%), tiredness (77%), loss of taste and smell (23%), rigors (93%), sweating (62%), and nausea (81%), but all tested negative for COVID-19 by PCR tests. Further examinations revealed additional and severe symptoms, such as sore throats (27%), body aches and pain (83%), diarrhea (11%), skin rashes (5%), eye irritation (21%), vomiting (42%), difficulty breathing (32%), and chest pain (67%). The sum of n = 1246 included the following: males, 289 were between 5 and 14 years, 183 (15–24 years), 157 (25–34 years), 113 (35–49 years), and 43 were 50+ years. Females: 138 were between 5 and 14 years, 93 (15–24 years), 72 (25–34 years), 89 (35–49 years), and 68 were 50+ years. The Gram-positive organisms isolated were Staphylococcus aureus (n = 111, 80.43%, MRSA 16.6%), E. faecalis (n = 20, 14.49%, VRE: 9.4%), and Streptococcus agalactiae (n = 7, 5.07%), while, Gram-negative organisms, such as E. coli (n = 135, 42.85%, CRE: 3.49%), K. pneumoniae (n = 93, 29.52%, CRE: 1.58%), P. aeruginosa (n = 43, 13.65%), C. freundii (n = 21, 6.66%), Serratia spp. (n = 8, 2.53%), and Proteus spp. (n = 15, 4.76%) were identified.
Publisher: MDPI AG
Date: 14-11-2022
Abstract: Background: Intussusception (ISN) post-COVID-19 infection in children is rare but can occur. SARS-CoV-2 may play a role in the pathogenesis of ISN and trigger immune activation and mesenteric adenitis, which predispose peristaltic activity to “telescope” a proximal bowel segment into the distal bowel lumen. Objectives: To estimate the prevalence of SARS-CoV-2 infection in ISN children and analyze the demographic parameters, clinical characteristics and treatment outcomes in ISN pediatric patients with COVID-19 illness. Methods: We performed this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting on the incidence of ISN post-SARS-CoV-2 infection in children, published from 1 December 2019 until 1 October 2022, in PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS and NATURE, with a restriction to articles available in the English language, were included. Results: Of the 169 papers that were identified, 34 articles were included in the systematic review and meta-analysis (28 case report, 5 cohort and 1 case-series studies). Studies involving 64 ISN patients with confirmed COVID-19 (all patients were children) were analyzed. The overall pooled proportions of the ISN patients who had PCR-confirmed SARS-CoV-2 infection was 0.06% (95% CI 0.03 to 0.09, n = 1790, four studies, I2 0%, p = 0.64), while 0.07% (95% CI 0.03 to 0.12, n = 1552, three studies, I2 0%, p = 0.47) had success to ISN pneumatic, hydrostatic and surgical reduction treatment and 0.04% (95% CI 0.00 to 0.09, n = 923, two studies, I2 0%, p = 0.97) had failure to ISN pneumatic, hydrostatic and surgical reduction treatment. The median patient age ranged from 1 to 132 months across studies, and most of the patients were in the 1–12 month age group (n = 32, 50%), p = 0.001. The majority of the patients were male (n = 41, 64.1%, p = 0.000) and belonged to White (Caucasian) (n = 25, 39.1%), Hispanic (n = 13, 20.3%) and Asian (n = 5, 7.8%) ethnicity, p = 0.000. The reported ISN classifications by location were mostly ileocolic (n = 35, 54.7%), and few children experienced ileo-ileal ISN (n = 4, 6.2%), p = 0.001. The most common symptoms from ISN were vomiting (n = 36, 56.2%), abdominal pain (n = 29, 45.3%), red currant jelly stools (n = 25, 39.1%) and blood in stool (n = 15, 23.4%). Half of the patients never had any medical comorbidities (n = 32, 50%), p = 0.036. The approaches and treatments commonly used to manage ISN included surgical reduction of the ISN (n = 17, 26.6%), pneumatic reduction of the ISN (n = 13, 20.2%), antibiotics (n = 12, 18.7%), hydrostatic reduction of the ISN (n = 11, 17.2%), laparotomy (n = 10, 15.6%), intravenous fluids (n = 8, 12.5%) and surgical resection (n = 5, 7.8%), p = 0.051. ISN was recurrent in two cases only (n = 2, 3.1%). The patients experienced failure to pneumatic (n = 7, 10.9%), hydrostatic (n = 6, 9.4%) and surgical (n = 1, 1.5%) ISN treatment, p = 0.002. The odds ratios of death were significantly higher in patients with a female gender (OR 1.13, 95% CI 0.31–0.79, p = 0.045), Asian ethnicity (OR 0.38, 95% CI 0.28–0.48, p 0.001), failure to pneumatic or surgical ISN reduction treatment (OR 0.11, 95% CI 0.05–0.21, p = 0.036), admission to ICU (OR 0.71, 95% CI 0.83–1.18, p = 0.03), intubation and placement of mechanical ventilation (OR 0.68, 95% CI 0.51–1.41, p = 0.01) or suffering from ARDS (OR 0.88, 95% CI 0.93–1.88, p = 0.01) compared to those who survived. Conclusion: Children with SARS-CoV-2 infection are at low risk to develop ISN. A female gender, Asian ethnicity, failure to ISN reduction treatment (pneumatic or surgical), admission to ICU, mechanical ventilation and suffering from ARDS were significantly associated with death following ISN in pediatric COVID-19 patients.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2023
DOI: 10.1186/S13223-023-00831-1
Abstract: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case–control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections–though the number of patients is small–but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
Publisher: F1000 Research Ltd
Date: 12-04-2022
DOI: 10.12688/F1000RESEARCH.109701.1
Abstract: Background: Although vaccination is underway, antiviral drugs against coronavirus disease 2019 (COVID-19) are lacking. Remdesivir, a nucleoside analog that works by inhibiting the viral RNA-dependent RNA polymerase (RdRp), is the only fully approved antiviral for the treatment of COVID-19. However, it is limited to intravenous use and is usually recommended only for hospitalized patients with severe COVID-19 therefore, oral drugs that can be prescribed even to non-hospitalized patients are required. According to a recent study, 4′-fluoruridine, a nucleoside analog similar to remdesivir, is a promising candidate for COVID-19 oral therapy due to its ability to stall viral RdRp. Methods: We examined the antiviral activity of 4′-fluorouridine and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been compiled and discussed in this review. Results: The 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vitro studies have shown that SARS-CoV-2 is susceptible to 4'-fluorouridine, with the half-maximal effective concentration (EC 50 ) of 0.2 to 0.6 M, and that the 4′-fluorouridine derivative, 4′-fluorouridine-5′-triphosphate, inhibited RdRp via a mechanism distinct from that of the already approved COVID-19 oral drug, molnupiravir. In addition, an in vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Conclusions: Concerns about the genetic effects of molnupiravir may be resolved by the use of 4′-fluorouridine and its derivative, which, unlike molnupiravir, do not alter genetics, but inhibit RdRp instead. Although they are currently considered as strong candidates, further studies are required to determine the antiviral activity of 4′-fluorouridine and its derivative against SARS-CoV-2 and their genetic effects on humans.
Publisher: MDPI AG
Date: 15-07-2022
DOI: 10.20944/PREPRINTS202207.0232.V1
Abstract: (1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.
Publisher: Informa UK Limited
Date: 07-2021
DOI: 10.2147/IJGM.S313757
Publisher: MDPI AG
Date: 08-06-2022
DOI: 10.3390/ANTIBIOTICS11060784
Abstract: Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of super-resistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI’s applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor’s prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains.
Publisher: MDPI AG
Date: 13-12-2022
Abstract: The novel coronavirus-19 (SARS-CoV-2), has infected numerous in iduals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an in idual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.
Publisher: MDPI AG
Date: 15-06-2021
DOI: 10.3390/DIAGNOSTICS11061091
Abstract: Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, s ling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large s le sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, s ling method, etc.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2022
Publisher: MDPI AG
Date: 28-11-2020
DOI: 10.3390/TROPICALMED5040180
Abstract: (Background) Lopinavir-ritonavir (LPV/RTV) is a human immunodeficiency virus (HIV) antiviral combination that has been considered for the treatment of COVID-19 disease. (Aim) This systematic review aimed to assess the efficacy and safety of LPV/RTV in COVID-19 patients in the published research. (Methods) A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Articles were selected for review from 8 electronic databases. This review evaluated the effects of LPV/RTV alone or in combination with standard care ± interferons/antiviral treatments compared to other therapies, regarding duration of hospital stay, risk of progressing to invasive mechanical, time to virological cure and body temperature normalization, cough relief, radiological progression, mortality and safety. (Results) A consensus was reached to select 32 articles for full-text screening only 14 articles comprising 9036 patients were included in this study and eight of these were included for meta-analysis. Most of these studies did not report positive clinical outcomes with LPV/RTV treatment. In terms of virological cure, three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral treatment (−0.81 day 95% confidence interval (CI), −4.44 to 2.81 p = 0.007, I2 = 80%). However, the overall effect was not significant (p = 0.66). When comparing the LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (p = 0.09). In terms of time to body normalization and cough relief, no favorable effects of LPV/RTV versus umifenovir were observed. The largest trials (RECOVERY and SOLIDARITY) have shown that LPV/RTV failed to reduce mortality, initiation of invasive mechanical ventilation or hospitalization duration. Adverse events were reported most frequently for LPV/RTV (n = 84) relative to other antivirals and no antiviral treatments. (Conclusions) This review did not reveal any significant advantage in efficacy of LPV/RTV for the treatment of COVID-19 over standard care, no antivirals or other antiviral treatments. This result might not reflect the actual evidence.
Publisher: Elsevier BV
Date: 04-2022
Publisher: MDPI AG
Date: 02-07-2022
Abstract: Given the increasing anti-vaccine movements erroneously touting vaccine danger, this review has investigated the rare adverse events potentially associated with BNT162b2 (Pfizer-BioNTech), an mRNA vaccine against the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Only real-world surveillance studies with at least 0.1 million BNT162b2-vaccinated participants and one unvaccinated control group were selected for review. A total of 21 studies examining the potential association of BNT162b2 with cardiovascular, herpetic, thrombotic or thrombocytopenic, neurological, mortality, and other miscellaneous rare adverse events were described in this review. Only myocarditis is consistently associated with BNT162b2. An unclear direction of association was seen with stroke (hemorrhagic and ischemic), herpes zoster, and paresthesia from BNT162b2, which may require more studies to resolve. Fortunately, most surveillance studies detected no increased risks of the remaining rare adverse events reviewed herein, further reassuring the safety of BNT162b2. In conclusion, this review has concisely summarized the current rare adverse events related and unrelated to BNT162b2, arguably for the first time in sufficient depth, to better communicate vaccine safety to the public.
Publisher: MDPI AG
Date: 19-08-2022
Abstract: Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more in iduals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.
Publisher: MDPI AG
Date: 26-08-2021
Abstract: Backgroundand Objectives: COVID-19 is a novel infectious disease caused by a single-stranded RNA coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to conduct a nationwide multicenter study to determine the characteristics and the clinical prognostic outcome of critically ill COVID-19 patients admitted to intensive care units (ICUs). Materials and Methods: This is a nationwide cohort retrospective study conducted in twenty Saudi hospitals. Results: An analysis of 1470 critically ill COVID-19 patients demonstrated that the majority of patients were male with a mean age of 55.9 ± 15.1 years. Most of our patients presented with a shortness of breath (SOB) (81.3%), followed by a fever (73.7%) and a cough (65.1%). Diabetes and hypertension were the most common comorbidities in the study (52.4% and 46.0%, respectively). Multiple complications were observed substantially more among non-survivors. The length and frequency of mechanical ventilation use were significantly greater (83%) in the non-survivors compared with the survivors (31%). The mean Sequential Organ Failure Assessment (SOFA) score was 6 ± 5. The overall mortality rate of the cohort associated with patients that had diabetes, hypertension and ischemic heart disease was 41.8%. Conclusion: Age a pre-existing medical history of hypertension, diabetes and ischemic heart disease smoking cigarettes a BMI ≥ 29 a long mechanical ventilation and ICU stay the need of ventilatory support a high SOFA score fungal co-infections and extracorporeal membrane oxygenation (ECMO) use were key clinical characteristics that predicted a high mortality in our population.
Publisher: Informa UK Limited
Date: 31-01-2022
Publisher: MDPI AG
Date: 17-10-2022
Abstract: Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus (DENV), which is transmitted through the mosquitoes Aedes aegypti and A. albopictus. The treatment of DF to date is only supportive and there is no definitive vaccine to prevent this disease. The non-structural DENV protein, RNA-dependent RNA Polymerase (RdRp), is involved in viral replication. The RdRp-derived peptides can be used in the construction of a universal dengue vaccine. These peptides can be utilized as epitopes to induce immunity. This study was an in silico evaluation of the affinity of the potential epitope for the universal dengue vaccine to dendritic cells and the bonds between the epitope and the dendritic cell receptor. The peptide sequence MGKREKKLGEFGKAKG generated from dengue virus subtype 2 (DENV-2) RdRp was antigenic, did not produce allergies, was non-toxic, and had no homology with the human genome. The potential epitope-based vaccine MGKREKKLGEFGKAKG binds stably to dendritic cell receptors with a binding free energy of −474,4 kcal/mol. This epitope is anticipated to induce an immunological response and has the potential to serve as a universal dengue virus vaccine candidate.
Publisher: PeerJ
Date: 02-09-2021
DOI: 10.7717/PEERJ.12119
Abstract: The burden of the spread of the COVID-19 pandemic has impacted widely on the healthcare providers physically and mentally. Many healthcare providers are exposed to psychological stressors due to their high risk of contracting the virus. This study aimed to measure the level of anxiety among healthcare providers during the COVID-19 pandemic in Saudi Arabia. In addition, this study aimed to measure the level of anxiety based on demographic characteristics. A cross-sectional survey was employed to recruit a convenience s le of healthcare providers. A pencil and paper self-administered questionnaires were used to collect data from demographic and generalized anxiety disorder GAD-7 data. However, this study received written informed consent from participants of the study. In addition, the study was approved by the Institutional Review Board at Dr. Sulaiman Al Habib Medical Group (IRB Log No. RC20.06.88-03). A total of 650 participants were recruited, results of GAD-7 showed that 43.5%, 28.9% and 27.5% of healthcare providers in Saudi Arabia experienced mild, moderate and severe anxiety, respectively, during the COVID-19 pandemic. Results indicated that age, health specialty, nationality, and sleeping disorders before COVID-19 were associated with anxiety levels. The generalized anxiety among healthcare providers in Saudi Arabia was mild. Older healthcare providers were found to have a higher level of anxiety compared to other participating healthcare providers. Several factors may contribute to a higher level of anxiety including age, socioeconomic status, marital status, having chronic conditions, and sleeping disorder before the COVID-19 pandemic. To further understand the level of anxiety among healthcare providers during the COVID-19 pandemic in Saudi Arabia, longitudinal and mixed-method research is needed.
Publisher: Informa UK Limited
Date: 22-07-2021
Publisher: MDPI AG
Date: 02-10-2022
Abstract: Since the first case of Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, SARS-CoV-2 infection has affected many in iduals worldwide. Eventually, some highly infectious mutants—caused by frequent genetic recombination—have been reported for SARS-CoV-2 that can potentially escape from the immune responses and induce long-term immunity, linked with a high mortality rate. In addition, several reports stated that vaccines designed for the SARS-CoV-2 wild-type variant have mixed responses against the variants of concern (VOCs) and variants of interest (VOIs) in the human population. These results advocate the designing and development of a panvaccine with the potential to neutralize all the possible emerging variants of SARS-CoV-2. In this context, recent discoveries suggest the design of SARS-CoV-2 panvaccines using nanotechnology, siRNA, antibodies or CRISPR-Cas platforms. Thereof, the present comprehensive review summarizes the current vaccine design approaches against SARS-CoV-2 infection, the role of genetic mutations in the emergence of new viral variants, the efficacy of existing vaccines in limiting the infection of emerging SARS-CoV-2 variants, and efforts or challenges in designing SARS panvaccines.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2021
DOI: 10.1186/S13098-021-00740-6
Abstract: One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA). To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA. A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis . We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient’s final treatment outcome (survival or death). Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399–638 mg/dl], 11.4% [IQR 9.9–13.5%], 7.16 [IQR 7.00–7.22], 10 mmol/l [IQR 6.9–13 mmol/l], and 24.5 mEq/l [18–29.2 mEq/l] respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27% p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07–15.19 p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38–7.91 p = 0.007], and male gender [OR 2.61, 95% CI 1.37–5.17 p = 0.004] compared to those who survived. DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are in iduals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level 1000 mg/dl, and anion gap ≥ 30 mEq/l.
Publisher: Cureus, Inc.
Date: 11-10-2020
DOI: 10.7759/CUREUS.10894
Publisher: MDPI AG
Date: 15-11-2022
DOI: 10.3390/TROPICALMED7110380
Abstract: Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06–8.17, I2 = 0% versus 5.31%, 95% CI 4.31–6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45–2.99, I2 = 0% versus 0.62%, 95% CI 0.00–1.55, I2 = 54%) however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70–4.34, I2 = 0% versus 4.91%, 95% CI 3.97–5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.
Publisher: PeerJ
Date: 17-05-2021
DOI: 10.7717/PEERJ.11469
Abstract: The outbreak of the novel Corona Virus Infectious Disease 2019 (COVID-19) has spread rapidly to many countries leading to thousands of deaths globally. The burden of this pandemic has affected the physical and mental health of the frontline health care workers (HCWs) who are exposed to high risk of infection and psychological stressors. The aim is to measure the level of depression among healthcare workers in Saudi Arabia during COVID-19 pandemic to establish interventional strategies. A descriptive cross-sectional study was used to conduct the current study. The data of this study was recruited between 15 June and 15 July 2020 from healthcare providers who work in both public and private healthcare sectors in Riyadh and Eastern province in Saudi Arabia utilizing a self-administered questionnaire. The study was approved by the Institutional Review Board at Dr. Sulaiman Al Habib Medical Group (IRB Log No. RC20.06.88-2). Data were collected by using The Zung Self-Rating Depression Scale SDS. A total of 900 healthcare providers working in the healthcare setting during COVID-19 pandemic were invited to participate in the study. A total of 650 healthcare providers participated in the study by completing and submitting the survey. Almost 30% suffered from depression which can be ided into three categories mild depression (26.2%), moderate/major (2.5%) and severe/extreme (0.8%). The finding shows that the level of depression among respondents at the age range of 31–40 years old was significantly higher than the level of depression among respondents with the age above 50 years old. Non-Saudi healthcare workers experienced more depression than Saudi workers. It also shows how nurses suffered from depression compared to their physician colleagues. Those who did not suffer from sleeping disorder perceived more depression as compared to those who are having sleeping disorder. It is recommended that health care facilities should implement strategies to reduce the prevalence of mental health problems among healthcare providers and eventually it will improve their performance in provision of safe and high-quality care for patients.
Publisher: MDPI AG
Date: 19-02-2022
DOI: 10.3390/ANTIBIOTICS11020276
Abstract: In addition to the pathogenesis of SARS-CoV-2, bacterial co-infection plays an essential role in the incidence and progression of SARS-CoV-2 infections by increasing the severity of infection, as well as increasing disease symptoms, death rate and antimicrobial resistance (AMR). The current study was conducted in a tertiary-care hospital in Lahore, Pakistan, among hospitalized COVID-19 patients to see the prevalence of bacterial co-infections and the AMR rates among different isolated bacteria. Clinical s les for the laboratory diagnosis were collected from 1165 hospitalized COVID-19 patients, of which 423 were found to be positive for various bacterial infections. Most of the isolated bacteria were Gram-negative rods (
Publisher: Informa UK Limited
Date: 08-03-2022
Publisher: Springer Science and Business Media LLC
Date: 03-06-2021
DOI: 10.1186/S13756-021-00957-0
Abstract: Knowledge of infection prevention and control (IPC) procedures among healthcare workers (HCWs) is crucial for effective IPC. Compliance with IPC measures has critical implications for HCWs safety, patient protection and the care environment. To discuss the body of available literature regarding HCWs' knowledge of IPC and highlight potential factors that may influence compliance to IPC precautions. A systematic review. A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis [PRISMA] statement. Electronic databases (PubMed, CINAHL, Embase, Proquest, Wiley online library, Medline, and Nature) were searched from 1 January 2006 to 31 January 2021 in the English language using the following keywords alone or in combination: knowledge, awareness, healthcare workers, infection, compliance, comply, control, prevention, factors . 3417 papers were identified and 30 papers were included in the review. Overall, the level of HCW knowledge of IPC appears to be adequate, good, and/or high concerning standard precautions, hand hygiene, and care pertaining to urinary catheters. Acceptable levels of knowledge were also detected in regards to IPC measures for specific diseases including TB, MRSA, MERS-CoV, COVID-19 and Ebola. However, gaps were identified in several HCWs' knowledge concerning occupational vaccinations, the modes of transmission of infectious diseases, and the risk of infection from needle stick and sharps injuries. Several factors for noncompliance surrounding IPC guidelines are discussed, as are recommendations for improving adherence to those guidelines. Embracing a multifaceted approach towards improving IPC-intervention strategies is highly suggested. The goal being to improve compliance among HCWs with IPC measures is necessary.
Publisher: MDPI AG
Date: 08-2022
DOI: 10.3390/COVID2080081
Abstract: Background: Acute Respiratory Distress Syndrome (ARDS) is caused by non-cardiogenic pulmonary edema and occurs in critically ill patients. It is one of the fatal complications observed among severe COVID-19 cases managed in intensive care units (ICU). Supportive lung-protective ventilation and prone positioning remain the mainstay interventions. Purpose: We describe the severity of ARDS, clinical outcomes, and management of ICU patients with laboratory-confirmed COVID-19 infection in multiple Saudi hospitals. Methods: A multicenter retrospective cohort study was conducted of critically ill patients who were admitted to the ICU with COVID-19 and developed ARDS. Results: During our study, 1154 patients experienced ARDS: 591 (51.2%) with severe, 415 (36.0%) with moderate, and 148 (12.8%) with mild ARDS. The mean sequential organ failure assessment (SOFA) score was significantly higher in severe ARDS with COVID-19 (6 ± 5, p = 0.006). Kaplan–Meier survival analysis showed COVID-19 patients with mild ARDS had a significantly higher survival rate compared to COVID-19 patients who experienced severe ARDS (p = 0.023). Conclusion: ARDS is a challenging condition complicating COVID-19 infection. It carries significant morbidity and results in elevated mortality. ARDS requires protective mechanical ventilation and other critical care supportive measures. The severity of ARDS is associated significantly with the rate of death among the patients.
Publisher: MDPI AG
Date: 10-08-2022
Abstract: Background: Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ. Objectives: To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection. Methods: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction. Results: One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male (n = 51, 53.1%) and were of White (Caucasian) (n = 51, 53.7%) and Hispanic (n = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech (n = 31), Moderna (n = 14), Oxford Uni-AstraZeneca (n = 10) and Sinovac-CoronaVac (n = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2–17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5–21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success (n = 70, 85.4%), graft failure (n = 12, 14.6%), survived (n = 90, 95.7%) and died (n = 4, 4.3%)]. Conclusion: The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2022
DOI: 10.1186/S12876-022-02507-3
Abstract: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.
Publisher: MDPI AG
Date: 21-07-2022
DOI: 10.20944/PREPRINTS202207.0314.V1
Abstract: Monkeypox is a rare disease which is rising nowadays in different countries since the first case in the UK was diagnosed on May 6, 2022, by the United Kingdom (UK) Health Security Agency. Then more than 12,500 cases were identified in over 68 countries up to July 18, 2022. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores in hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more liable to be affected than others. The exact pathogenesis and mechanisms are still unclear however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of the cases. Also, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S40001-021-00618-3
Abstract: Extracorporeal membrane oxygenation (ECMO) has been used as a rescue strategy in patients with severe with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection, but there has been little evidence of its efficacy. To describe the effect of ECMO rescue therapy on patient-important outcomes in patients with severe SARS-CoV-2. A case series study was conducted for the laboratory-confirmed SARS-CoV-2 patients who were admitted to the ICUs of 22 Saudi hospitals, between March 1, 2020, and October 30, 2020, by reviewing patient’s medical records prospectively. ECMO use was associated with higher in-hospital mortality (40.2% vs. 48.9% p = 0.000) lower COVID-19 virological cure (41.3% vs 14.1%, p = 0.000) and longer hospitalization (20.2 days vs 29.1 days p = 0.000), ICU stay (12.6 vs 26 days p = 0.000) and mechanical ventilation use (14.2 days vs 22.4 days p = 0.000) compared to non-ECMO group. Also, there was a high number of patients with septic shock (19.6%) and multiple organ failure (10.9%) and more complications occurred at any time during hospitalization [pneumothorax (5% vs 29.3%, p = 0.000), bleeding requiring blood transfusion (7.1% vs 38%, p = 0.000), pulmonary embolism (6.4% vs 15.2%, p = 0.016), and gastrointestinal bleeding (3.3% vs 8.7%, p = 0.017)] in the ECMO group. However, PaO 2 was significantly higher in the 72-h post-ECMO initiation group and PCO 2 was significantly lower in the 72-h post-ECMO start group than those in the 12-h pre-ECMO group (62.9 vs. 70 mmHg, p = 0.002 and 61.8 vs. 51 mmHg, p = 0.042, respectively). Following the use of ECMO, the mortality rate of patients and length of ICU and hospital stay were not improved. However, these findings need to be carefully interpreted, as most of our cohort patients were relatively old and had multiple severe comorbidities. Future randomized trials, although challenging to conduct, are highly needed to confirm or dispute reported observations.
Publisher: Informa UK Limited
Date: 31-01-2022
Publisher: African Journals Online (AJOL)
Date: 06-11-2015
Publisher: MDPI AG
Date: 29-08-2022
Abstract: (1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods and Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses—ACAM2000, JYNNEOS, and LC16—with the first being a replicating vaccine and the latter being non- or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental immunity to MPV. ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer complications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or developed into a mRNA vaccine before monkeypox is declared a pandemic.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2021
DOI: 10.1186/S40001-021-00517-7
Abstract: COVID-19 is a worldwide pandemic and has placed significant demand for acute and critical care services on hospitals in many countries. To determine the predictors of severe COVID-19 disease requiring admission to an ICU by comparing patients who were ICU admitted to non-ICU groups. A cohort study was conducted for the laboratory-confirmed COVID-19 patients who were admitted to six Saudi Ministry of Health’s hospitals in Alahsa, between March 1, 2020, and July 30, 2020, by reviewing patient’s medical records retrospectively. This cohort included 1014 patients with an overall mean age of 47.2 ± 19.3 years and 582 (57%) were males. A total of 205 (20%) of the hospitalized patients were admitted to the ICU. Hypertension, diabetes and obesity were the most common comorbidities in all study patients (27.2, 19.9, and 9%, respectively). The most prevalent symptoms were cough (47.7%), shortness of breath (35.7%) and fever (34.3%). Compared with non-ICU group, ICU patients had older age ( p ≤ 0.0005) and comprised a higher proportion of the current smokers and had higher respiratory rates ( p ≤ 0.0005), and more percentage of body temperatures in the range of 37.3–38.0 °C ( p ≥ 0.0005) and had more comorbidities including diabetes ( p ≤ 0.0005), hypertension ( p ≥ 0.0005), obesity ( p = 0.048), and sickle cell disease ( p = 0.039). There were significant differences between the non-ICU and ICU groups for fever, shortness of breath, cough, fatigue, vomiting, dizziness elevated white blood cells, neutrophils, alanine aminotransferase and alkaline aminotransferase, lactate dehydrogenase, and ferritin, and decreased hemoglobin and proportion of abnormal bilateral chest CT images ( p 0.05). Significant differences were also found for multiple treatments ( p 0.05). ICU patients group had a much higher mortality rate than those with non-ICU admission ( p ≤ 0.0005). Identifying key clinical characteristics of COVID-19 that predict ICU admission and high mortality can be useful for frontline healthcare providers in making the right clinical decision under time-sensitive and resource-constricted environment.
Publisher: MDPI AG
Date: 17-08-2022
DOI: 10.3390/PATHOGENS11080924
Abstract: Monkeypox is a rare disease but is increasing in incidence in different countries since the first case was diagnosed in the UK by the United Kingdom (UK) Health Security Agency on 6 May 2022. As of 9 August, almost 32,000 cases have been identified in 89 countries. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores on the hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more likely to be infected than others. The exact pathogenesis and mechanisms are still unclear however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of cases. Moreover, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2020
DOI: 10.1186/S40001-020-00462-X
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged from China in December 2019 and has presented as a substantial and serious threat to global health. We aimed to describe the clinical, epidemiological, and laboratory findings of patients in Saudi Arabia infected with SARS-CoV-2 to direct us in helping prevent and treat coronavirus disease 2019 (COVID-19) across Saudi Arabia and around the world. Clinical, epidemiological, laboratory, and radiological characteristics, treatment, and outcomes of pediatric and adult patients in five hospitals in Riyadh, Saudi Arabia, were surveyed in this study. 401 patients (mean age 38.16 ± 13.43 years) were identified to be SARS-CoV-2 positive and 80% of cases were male. 160 patients had moderate severity and 241 were mild in severity. The most common signs and symptoms at presentation were cough, fever, fatigue, and shortness of breath. Neutrophil and lymphocyte counts, aspartate aminotransferase, C-reactive protein, and ferritin were higher in the COVID-19 moderate severity patient group. Mild severity patients spent a shorter duration hospitalized and had slightly higher percentages of abnormal CT scans and X-ray imaging. This study provides an understanding of the features of non-ICU COVID-19 patients in Saudi Arabia. Further national collaborative studies are needed to streamline screening and treatment procedures for COVID-19.
Publisher: MDPI AG
Date: 20-05-2022
Abstract: Measles is an RNA virus infectious disease mainly seen in children. Despite the availability of an effective vaccine against measles, it remains a health issue in children. Although it is a self-limiting disease, it becomes severe in undernourished and immune-compromised in iduals. Measles infection is associated with secondary infections by opportunistic bacteria due to the immunosuppressive effects of the measles virus. Recent reports highlight that measles infection erases the already existing immune memory of various pathogens. This review covers the incidence, pathogenesis, measles variants, clinical presentations, secondary infections, elimination of measles virus on a global scale, and especially the immune responses related to measles infection.
Publisher: MDPI AG
Date: 05-06-2013
DOI: 10.3390/ANTIBIOTICS11040516
Abstract: The high rates of bacterial infections affect the economy worldwide by contributing to the increase in morbidity and treatment costs. The present cross-sectional study was carried out to evaluate the prevalence of bacterial infection in urinary tract infection (UTI) patients and to evaluate the antimicrobial resistance rate (AMR) in a Tertiary Care Hospital in Lahore, Pakistan. The study was conducted for the period of one year from January 2020 to December 2020. A total of 1899 different clinical s les were collected and examined for bacterial cultures using standard procedures. S les were inoculated on different culture media to isolate bacterial isolates and for identification and susceptibility testing. A total of 1107/1899 clinical s les were positive for Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and other bacterial isolates. Methicillin-resistant S. aureus (MRSA) prevalence was 16.93% from these positive cases. MRSA strains were found to be highly resistant to amikacin, clindamycin, fusidic acid, gentamicin and tobramycin, while highest sensitivity was noted against vancomycin (100%) and linezolid (100%). MRSA and high rates of multidrug resistance (MDR) pose a serious therapeutic burden to critically ill patients. A systematic and concerted effort is essential to rapidly identify high-risk patients and to reduce the burden of AMR.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2020
DOI: 10.1186/S13756-020-00751-4
Abstract: Antimicrobial stewardship (AMS) programs have shown to reduce the emergence of antimicrobial resistance (AMR) and health-care-associated infections (HAIs), and save health-care costs associated with an inappropriate antimicrobial use. The primary objective of this study was to compare the consumption and cost of antimicrobial agents using defined daily dose (DDD) and direct cost of antibiotics before and after the AMS program implementation. Secondary objective was to determine the rate of HAIs [ Clostridium difficile ( C. difficile ), ventilator-associated pneumonia (VAP), and central line-associated bloodstream infection (CLABSI) before and after the AMS program implementation. This is a pre-post quasi-experimental study. Adult inpatients were enrolled in a prospective fashion under the active AMS arm and compared with historical inpatients who were admitted to the same units before the AMS implementation. Study was conducted at four tertiary private hospitals located in two cities in Saudi Arabia. Adult inpatients were enrolled under the pre- AMS arm and post- AMS arm if they were on any of the ten selected restricted broad-spectrum antibiotics (imipenem/cilastatin, piperacillin/tazobactam, colistin, tigecycline, cefepime, meropenem, ciprofloxacin, moxifloxacin, teicoplanin and linezolid). A total of 409,403 subjects were recruited, 79,369 in the pre- AMS control and 330,034 in the post- AMS arm. Average DDDs consumption of all targeted broad-spectrum antimicrobials from January 2016 to June 2019 post- AMS launch was lower than the DDDs use of these agents pre- AMS (233 vs 320 DDDs per 1000 patient-days, p = 0.689). Antimicrobial expenditures decreased by 28.45% in the first year of the program and remained relatively stable in subsequent years, with overall cumulative cost savings estimated at S.R. 6,286,929 and negligible expenses of S.R. 505,115 ( p = 0.648). Rates of healthcare associated infections involving C. difficile , VAP, and CLABSI all decreased significantly after AMS implementation (incidence of HAIs in 2015 compared to 2019: for C. difficile , 94 vs 13, p = 0.024 for VAP, 24 vs 6, p = 0.001 for CLABSI, 17 vs 1, p = 0.000 respectively). Implementation of AMS program at HMG healthcare facilities resulted in reduced antimicrobials use and cost, and lowered incidence of healthcare associated infections.
Publisher: Wiley
Date: 26-08-2022
DOI: 10.1002/RMV.2391
Abstract: Several nations have recently begun to relax their public health protocols, particularly regarding the use of face masks when engaging in outdoor activities. This is because there has been a general trend towards fewer cases of coronavirus disease 2019 (COVID‐19). However, new Omicron sub‐variants (designated BA.4 and BA.5) have recently emerged. These two subvariants are thought to be the cause of an increase in COVID‐19 cases in South Africa, the United States, and Europe. They have also begun to spread throughout Asia. They evolved from the Omicron lineage with characteristics that make them even more contagious and which allow them to circumvent immunity from a previous infection or vaccination. This article reviews a number of scientific considerations about these new variants, including their apparently reduced clinical severity.
Publisher: MDPI AG
Date: 31-12-2022
Abstract: The Human Immunodeficiency Virus (HIV) is a highly morphic, retrovirus that rapidly evolves through mutation as well as recombination. Because of the immunocompromised status in HIV patients, there is often a higher chance of acquiring different secondary infections followed by liver cirrhosis, hepatitis B & C, and HIV-associated nephropathy. The current study was conducted to see the prevalence of secondary infections, hematological and biochemical markers for liver and renal associated diseases, and to detect the envelope gene (GP41) in newly diagnosed HIV patients. A total of 37 s les were collected from HIV-positive patients registered in different hospital settings under the National AIDS control program. The collected s les were processed for hepatitis B, hepatitis C, hematological analysis, and biochemical analysis. To identify the envelope gene in newly diagnosed HIV patients, polymerase chain reaction (PCR) was performed using four gene-specific primers. The HIV infections were seen more in male as compared to females. A significant decrease in complete blood count was observed in HIV patients when compared to healthy in iduals. There was a significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine observed in HIV patients. No significant difference was observed in alkaline phosphatase (ALP), total bilirubin, and albumin levels when compared to healthy control. Anemia was observed in 59.4% of HIV patients. A total of three (8.1%) patients were found to be co-infected with hepatitis B and one (2.7 %) was co-infected with hepatitis C. Out of these 37 tested s les, a total of four showed the successful lification of the envelope gene. This study provides platform for the health care facilitators to regularly monitor the signs, symptoms and clinical biomarkers of HIV-associated infections to prevent toxicity at an early stage to improve the quality of life (QoL) and minimize the mortality rate in HIV patients. Envelope gene mutating frequently results in drug resistance, and thus future research on polymorphism analysis will reveal points of substitutions to improve drug designing.
Publisher: MDPI AG
Date: 06-07-2022
Abstract: Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical s les were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cultures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected s les, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and icillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococcus (VRE) was 3.96%. Conclusions: The results of the current study conclude that empiric antimicrobial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months.
Publisher: MDPI AG
Date: 17-10-2022
DOI: 10.3390/MOLECULES27206985
Abstract: Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen’s favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2021
DOI: 10.1186/S13223-021-00613-7
Abstract: Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis , non-anaphylaxis , anaphylactic reaction , nonanaphylactic reaction , anaphylactic/anaphylactoid shock , hypersensitivity , allergy reaction , allergic reaction , immunology reaction , immunologic reaction , angioedema , loss of consciousness , generalized erythema , urticaria , urticarial rash , cyanosis , grunting , stridor , tachypnoea , wheezing , tachycardia , abdominal pain , diarrhea , nausea , vomiting and tryptase . We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I 2 = 81%, p = 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I 2 = 99%, p = 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I 2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I 2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I 2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I 2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry by producing p values 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important. The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.
Publisher: Public Library of Science (PLoS)
Date: 28-04-2022
DOI: 10.1371/JOURNAL.PONE.0266277
Abstract: COVID-19 household transmissibility remains unclear in Pakistan. To understand the dynamics of Severe Acute Respiratory Syndrome Coronavirus disease epidemiology, this study estimated Secondary Attack Rate (SAR) among household and close contacts of index cases in Pakistan using a statistical transmission model. A retrospective cohort study was conducted using an inclusive contact tracing dataset from the provinces of Punjab and Khyber-Pakhtunkhwa to estimate SAR. We considered the probability of an infected person transmitting the infection to close contacts regardless of residential addresses. This means that close contacts were identified irrespective of their relationship with the index case. We assessed demographic determinants of COVID-19 infectivity and transmissibility. For this purpose based on evolving evidence, and as CDC recommends fully vaccinated people get tested 5–7 days after close contact with a person with suspected or confirmed COVID-19. Therefore we followed the same procedure in the close contacts for secondary infection. During the study period from 15 th May 2020 to 15 th Jan 2021, a total of 339 (33.9%) index cases were studied from 1000 cases initially notified. Among close contact groups (n = 739), households were identified with an assumed mean incubation period of 8.2+4.3 days and a maximum incubation period of 15 days. SAR estimated here is among the household contacts. 117 secondary cases from 739 household contacts, with SAR 11.1% (95% CI 9.0–13.6). All together (240) SAR achieved was 32.48% (95% CI 29.12–37.87) for symptomatic and confirmed cases. The potential risk factors for SAR identified here included old age group ( years of age), male (gender), household members , and residency in urban areas and for index cases high age group. Overall local reproductive number (R) based on the observed household contact frequencies for index rimary cases was 0.9 (95% CI 0.47–1.21) in Khyber Pakhtunkhwa and 1.3 (95% CI 0.73–1.56) in Punjab. SAR estimated here was high especially in the second phase of the COVID-19 pandemic in Pakistan. The results highlight the need to adopt rigorous preventive measures to cut the chain of viral transmission and prevent another wave of COVID-19.
Publisher: Informa UK Limited
Date: 31-01-2022
Publisher: Springer Science and Business Media LLC
Date: 12-06-2021
DOI: 10.1186/S12941-021-00450-X
Abstract: Studying time-related changes in susceptible pathogens causing healthcare-associated infections (HAIs) is vital in improving local antimicrobial and infection control practices. Describe susceptibility patterns to several antimicrobials in gram-positive and gram-negative pathogens isolated from patients causing HAIs at three private tertiary care hospitals in Saudi Arabia over a 5-year period. Data on trends of antimicrobial susceptibility among bacteria causing HAIs events in children and adults at three tertiary private hospitals located in Riyadh and Qassim, Saudi Arabia, were collected retrospectively between 2015 and 2019 using the surveillance data datasets. Over a 5-year period, 38,624 pathogens caused 17,539 HAI events in 17,566 patients. About 9450 (53.8%) of patients who suffered HAIs were females and the average age was 41.7 ± 14.3 years (78.1% were adults and 21.9% were children). Gram-negative pathogens were 2.3-times more likely to cause HAIs compared to gram-positive bacteria (71.9% vs. 28.1%). The ranking of causative pathogens in decreasing order was: Escherichia coli (38%), Klebsiella species (15.1%), and Staphylococcus aureus (12.6%). Gram-positive isolates were mostly susceptible to linezolid (91.8%) whereas they were resistant to icillin (52.6%), cefoxitin (54.2%), and doxycycline (55.9%). Gram-negative isolates were mostly sensitive to tigecycline (95%) whereas they were resistant to cefotaxime (49.5%) and cefixime (59.6%). During the 5 years, there were relatively stable susceptibility patterns to all tested antimicrobials, except for cefotaxime which shown a susceptibility reduction by 41.4%, among Escherichia coli and Klebsiella species. An increase in the susceptibility of Acinetobacter and Enterobacter and Citrobacter species to all studied antimicrobials was observed except for colistin that had a slight sensitivity reduction in 2019 by 4.3% against Acinetobacter species. However, we noted reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin and increased resistance of MRSA to linezolid and vancomycin. The observed increase in susceptibility of gram-positive and gram-negative bacteria to studied antimicrobials is important however, reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin and increased resistance of MRSA to linezolid and vancomycin is a serious threat and calls for effective antimicrobial stewardship programs.
Publisher: MDPI AG
Date: 21-06-2022
Abstract: COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the survivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some of the complications observed in infected patients post COVID-19 recovery. These health abnormalities, including is multiple organ failure-the most striking pathological features of COVID-19-have been linked with erse distribution of ACE2 receptor. Additionally, several health complications reports were reported after administration of COVID-19 vaccines in healthy in iduals, but clinical or molecular pathways causing such complications are not yet studied in detail. Thus, the present systematic review established the comparison of health complication noted in vaccinated and non-vaccinated in iduals (COVID-19 infected patients) to identify the association between vaccination and the multiorgan failure based on the data obtained from case studies, research articles, clinical trials/Cohort based studies and review articles published between 2020-2022. This review also includes the biological rationale behind the COVID-19 infection and its subsequent symptoms and effects including multiorgan failure. In addition, multisystem inflammatory syndrome (MIS) has been informed in in iduals post vaccination that resulted in multiorgan failure but, no direct correlation of vaccination with MIS has been established. Similarly, hemophagocytic lymphohistiocytosis (HLH) also noted to cause multiorgan failure in some in iduals following full vaccination. Furthermore, severe complications were recorded in elderly patients (+40 years of age), indicates that older age in iduals are higher risk by COVID-19 and post vaccination, but available literature is not sufficient to comply with any conclusive statements on relationship between vaccination and multiorgan failure.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2022
DOI: 10.1186/S13027-022-00459-7
Abstract: Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient’s final treatment outcome (survival or death). Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I 2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I 2 94%, p 0.01). The median patient age ranged from 51.6 years to 80 years across studies. The majority of the patients were male ( n = 2243, 66.7%) and belonged to White (Caucasian) ( n = 262, 7.8%), Hispanic ( n = 156, 4.6%) and Asian ( n = 153, 4.4%) ethnicity. The main source of SARS-CoV-2 infection in CRC patients was community-acquired ( n = 2882, 85.7% p = 0.014). Most of those SARS-CoV-2 patients had stage III CRC ( n = 725, 21.6% p = 0.036) and were treated mainly with surgical resections (n = 304, 9%) and chemotherapies ( n = 187, 5.6%), p = 0.008. The odd ratios of death were significantly high in patients with old age (≥ 60 years) (OR 1.96, 95% CI 0.94–0.96 p 0.001), male gender (OR 1.44, 95% CI 0.41–0.47 p 0.001) CRC stage III (OR 1.54, 95% CI 0.02–1.05 p = 0.041), CRC stage IV (OR 1.69, 95% CI 0.17–1.2 p = 0.009), recent active treatment with chemotherapies (OR 1.35, 95% CI 0.5–0.66 p = 0.023) or surgical resections (OR 1.4, 95% CI 0.8–0.73 p = 0.016) and admission to ICU (OR 1.88, 95% CI 0.85–1.12 p 0.001) compared to those who survived. SARS-CoV-2 infection in CRC patient is not uncommon and results in a mortality rate of 26.2%. Key determinants that lead to increased mortality in CRC patients infected with COVID-19 include older age (≥ 60 years old) male gender Asian and Hispanic ethnicity if SARS-CoV-2 was acquired from hospital source advanced CRC (stage III and IV) if patient received chemotherapies or surgical treatment and if patient was admitted to ICU, ventilated or experienced ARDS.
Publisher: MDPI AG
Date: 14-11-2022
Abstract: As medical science and technology progress towards the era of “big data”, a multi-dimensional dataset pertaining to medical diagnosis and treatment is becoming accessible for mathematical modelling. However, these datasets are frequently inconsistent, noisy, and often characterized by a significant degree of redundancy. Thus, extensive data processing is widely advised to clean the dataset before feeding it into the mathematical model. In this context, Artificial intelligence (AI) techniques, including machine learning (ML) and deep learning (DL) algorithms based on artificial neural networks (ANNs) and their types, are being used to produce a precise and cross-sectional illustration of clinical data. For prostate cancer patients, datasets derived from the prostate-specific antigen (PSA), MRI-guided biopsies, genetic biomarkers, and the Gleason grading are primarily used for diagnosis, risk stratification, and patient monitoring. However, recording diagnoses and further stratifying risks based on such diagnostic data frequently involves much subjectivity. Thus, implementing an AI algorithm on a PC’s diagnostic data can reduce the subjectivity of the process and assist in decision making. In addition, AI is used to cut down the processing time and help with early detection, which provides a superior outcome in critical cases of prostate cancer. Furthermore, this also facilitates offering the service at a lower cost by reducing the amount of human labor. Herein, the prime objective of this review is to provide a deep analysis encompassing the existing AI algorithms that are being deployed in the field of prostate cancer (PC) for diagnosis and treatment. Based on the available literature, AI-powered technology has the potential for extensive growth and penetration in PC diagnosis and treatment to ease and expedite the existing medical process.
Publisher: MDPI AG
Date: 16-08-2022
DOI: 10.3390/TROPICALMED7080188
Abstract: A reliable estimate of Candida parapsilosis antifungal susceptibility in candidemia patients is increasingly important to track the spread of C. parapsilosis bloodstream infections and define the true burden of the ongoing antifungal resistance. A systematic review and meta-analysis (SRMA) were conducted aiming to estimate the global prevalence and identify patterns of antifungal resistance. A systematic literature search of the PubMed, Scopus, ScienceDirect and Google Scholar electronic databases was conducted on published studies that employed antifungal susceptibility testing (AFST) on clinical C. parapsilosis isolates globally. Seventy-nine eligible studies were included. Using meta-analysis of proportions, the overall pooled prevalence of three most important antifungal drugs Fluconazole, Amphotericin B and Voriconazole resistant C. parapsilosis were calculated as 15.2% (95% CI: 9.2–21.2), 1.3% (95% CI: 0.0–2.9) and 4.7% (95% CI: 2.2–7.3), respectively. Based on study enrolment time, country/continent and AFST method, subgroup analyses were conducted for the three studied antifungals to determine sources of heterogeneity. Timeline and regional differences in C. parapsilosis prevalence of antifungal resistance were identified with the same patterns among the three antifungal drugs. These findings highlight the need to conduct further studies to assess and monitor the growing burden of antifungal resistance, to revise treatment guidelines and to implement regional surveillance to prevent further increase in C. parapsilosis drug resistance emerging recently.
Publisher: MDPI AG
Date: 22-08-2022
DOI: 10.3390/MOLECULES27165335
Abstract: Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers’ interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.
Publisher: MDPI AG
Date: 27-08-2021
Abstract: Background: Population-based studies from several countries have constantly shown excessively high rates of medication errors and avoidable deaths. An efficient medication error reporting system is the backbone of reliable practice and a measure of progress towards achieving safety. Improvement efforts and system changes of medication error reporting systems should be targeted towards reductions in the likelihood of injury to future patients. However, the aim of this review is to provide a summary of medication errors reporting culture, incidence reporting systems, creating effective reporting methods, analysis of medication error reports, and recommendations to improve medication errors reporting systems. Methods: Electronic databases (PubMed, Ovid, EBSCOhost, EMBASE, and ProQuest) were examined from 1 January 1998 to 30 June 2020. 180 articles were found and 60 papers were ultimately included in the review. Data were mined by two reviewers and verified by two other reviewers. The search yielded 684 articles, which were then reduced to 60 after the deletion of duplicates via vetting of titles, abstracts, and full-text papers. Results: Studies were principally from the United States of America and the United Kingdom. Limited studies were from Canada, Australia, New Zealand, Korea, Japan, Greece, France, Saudi Arabia, and Egypt. Detection, measurement, and analysis of medication errors require an active rather than a passive approach. Efforts are needed to encourage medication error reporting, including involving staff in opportunities for improvement and the determination of root cause(s). The National Coordinating Council for Medication Error Reporting and Prevention taxonomy is a classification system to describe and analyze the details around in idual medication error events. Conclusion: A successful medication error reporting program should be safe for the reporter, result in constructive and useful recommendations and effective changes while being inclusive of everyone and supported with required resources. Health organizations need to adopt an effectual reporting environment for the medication use process in order to advance into a sounder practice.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1186/S13099-021-00414-8
Abstract: Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs). To re-assess the association between PPIs use and SBP incidence with larger and better-quality data. The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity. A total of twenty-three studies: seven case–control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p 0.00001) but still statistically significant and with high heterogeneity (Chi 2 p = 57.68 I 2 = 74%). For case–control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger’s test confirmed asymmetry suggesting publication bias (intercept = − 0.05, SE = 0.27, P = 0.850 two-tailed). This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
Publisher: MDPI AG
Date: 19-11-2022
Abstract: Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected in iduals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JNUTBIO.2019.02.009
Abstract: Uteroplacental insufficiency-induced low birth weight (LBW) and postnatal high saturated fat/high sucrose-fructose diet (Western Diet, WD) consumption have been independently associated with the development of hepatic steatosis, while their additive effect on fatty acid, acylcarnitine and amino acid profiles in early adulthood have not been widely reported. We employed LBW, generated via uterine artery ablation, and normal birth weight (NBW) male guinea pigs fed either a WD or control diet (CD) from weaning to postnatal day 150 (early adulthood). Hepatic steatosis was absent in CD-fed offspring, while NBW/WD offspring displayed macrovesicular steatosis and LBW/WD offspring exhibited microvesicular steatosis, both occurring in a lean phenotype. Life-long consumption of the WD, irrespective of birth weight, was associated with an increase in hepatic medium- and long-chain saturated fatty acids, monounsaturated fatty acids, acylcarnitines, reduced oxidative phosphorylation complex III activity and polyunsaturated fatty acids, and molecular evidence of disrupted hepatic insulin signaling. In NBW/WD, hepatic C15:1 and C16:1n-6 fatty acids in phospholipids, C16, C18 and C18:1 acylcarnitines, concentrations of aspartate, phenylalanine, tyrosine and tryptophan and expression of carnitine palmitoyltransferase 1 alpha (CPT1α) and uncoupling protein 2 (UCP2) genes were elevated compared to LBW/WD livers. Our results suggest that LBW and life-long WD combined are influential in promoting hepatic microvesicular steatosis in conjunction with a specific mitochondrial gene expression and metabolomic profile in early adulthood.
Publisher: MDPI AG
Date: 21-06-2022
DOI: 10.3390/PATHOGENS11070712
Abstract: In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1–6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients’ liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.
Publisher: MDPI AG
Date: 05-07-2022
DOI: 10.3390/MOLECULES27134305
Abstract: The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease.
Publisher: MDPI AG
Date: 29-05-2022
Abstract: Human Parainfluenza Virus (HPIV) Type-1, which is an anti-sense ribonucleic acid (RNA) virus belonging to the paramyxoviridae family, induces upper and lower respiratory tract infections. The infections caused by the HPIV Type-1 virus are usually confined to northwestern regions of America. HPIV-1 causes infections through the virulence of the hemagglutinin-neuraminidase (HN) protein, which plays a key role in the attachment of the viral particle with the host’s receptor cells. To the best of our knowledge, there is no effective antiviral drugs or vaccines being developed to combat the infection caused by HPIV-1. In the current study, a multiple epitope-based vaccine was designed against HPIV-1 by taking the viral HN protein as a probable vaccine candidate. The multiple epitopes were selected in accordance with their allergenicity, antigenicity and toxicity scoring. The determined epitopes of the HN protein were connected simultaneously using specific conjugates along with an adjuvant to construct the subunit vaccine, with an antigenicity score of 0.6406. The constructed vaccine model was docked with various Toll-like Receptors (TLRs) and was computationally cloned in a pET28a (+) vector to analyze the expression of vaccine sequence in the biological system. Immune stimulations carried out by the C-ImmSim Server showed an excellent result of the body’s defense system against the constructed vaccine model. The AllerTop tool predicted that the construct was non-allergen with and without the adjuvant sequence, and the VaxiJen 2.0 with 0.4 threshold predicted that the construct was antigenic, while the Toxinpred predicted that the construct was non-toxic. Protparam results showed that the selected protein was stable with 36.48 instability index (II) scores. The Grand average of Hydropathicity or GRAVY score indicated that the constructed protein was hydrophilic in nature. Aliphatic index values (93.53) confirmed that the construct was thermostable. This integrated computational approach shows that the constructed vaccine model has a potential to combat laryngotracheobronchitis infections caused by HPIV-I.
Publisher: MDPI AG
Date: 18-08-2022
Abstract: Antibodies (Abs) are important immune mediators and powerful diagnostic markers in a wide range of infectious diseases. Understanding the humoral immunity or the development of effective antibodies against SARS-CoV-2 is a prerequisite for limiting disease burden in the community and aids in the development of new diagnostic, therapeutic, and vaccination options. Accordingly, the role of antiviral antibodies in the resistance to and diagnosis of SARS-CoV-2 infection was explored. Antibody testing showed the potential in adding important diagnostic value to the routine diagnosis and clinical management of COVID-19. They could also play a critical role in COVID-19 surveillance, allowing for a better understanding of the full scope of the disease. The development of several vaccines and the success of passive immunotherapy suggest that anti-SARS-CoV-2 antibodies have the potential to be used in the treatment and prevention of SARS-CoV-2 infection. In this review, we highlight the role of antibodies in the diagnosis of SARS-CoV-2 infection and provide an update on their protective roles in controlling SARS-CoV-2 infection as well as vaccine development.
Publisher: MDPI AG
Date: 12-2022
Abstract: Background: Tixagevimab/cilgavimab (TGM/CGM) are neutralizing monoclonal antibodies (mAbs) directed against different epitopes of the receptor-binding domain of the SARS-CoV-2 spike protein that have been considered as pre-exposure prophylaxis (PrEP). Objectives: This study seeks to assess the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at high risk for breakthrough and severe SARS-CoV-2 infection who never benefited maximally from SARS-CoV-2 vaccination and for those who have a contraindication to SARS-CoV-2 vaccines. Design: This study is a systematic review and meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Methods: Electronic databases (PubMed, CINAHL, Embase, medRxiv, ProQuest, Wiley online library, Medline, and Nature) were searched from 1 December 2021 to 30 November 2022 in the English language using the following keywords alone or in combination: 2019-nCoV, 2019 novel coronavirus, COVID-19, coronavirus disease 2019, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, tixagevimab, cilgavimab, combination, monoclonal, passive, immunization, antibody, efficacy, clinical trial, cohort, pre-exposure, prophylaxis, and prevention. We included studies in moderate to severe immunocompromised adults (aged ≥18 years) and children (aged ≥12 years) who cannot be vaccinated against COVID-19 or may have an inadequate response to SARS-CoV-2 vaccination. The effect sizes of the outcome of measures were pooled with 95% confidence intervals (CIs) and risk ratios (RRs). Results: Of the 76 papers that were identified, 30 articles were included in the qualitative analysis and 13 articles were included in the quantitative analysis (23 cohorts, 5 case series, 1 care report, and 1 randomized clinical trial). Studies involving 27,932 patients with high risk for breakthrough and severe COVID-19 that reported use of TGM/CGM combination were analyzed (all were adults (100%), 62.8% were men, and patients were mainly immunocompromised (66.6%)). The patients’ ages ranged from 19.7 years to 79.8 years across studies. TGM/CGM use was associated with lower COVID-19-related hospitalization rate (0.54% vs. 1.2%, p = 0.27), lower ICU admission rate (0.6% vs. 5.2%, p = 0.68), lower mortality rate (0.2% vs. 1.2%, p = 0.67), higher neutralization of COVID-19 Omicron variant rate (12.9% vs. 6%, p = 0.60), lower proportion of patients who needed oxygen therapy (8% vs. 41.2%, p = 0.27), lower RT-PCR SARS-CoV-2 positivity rate (2.1% vs. 5.8%, p 0.01), lower proportion of patients who had severe COVID-19 (0% vs. 0.5%, p = 0.79), lower proportion of patients who had symptomatic COVID-19 (1.8% vs. 6%, p = 0.22), and higher adverse effects rate (11.1% vs. 10.7%, p = 0.0066) than no treatment or other alternative treatment in the prevention of COVID-19. Conclusion: For PrEP, TGM/CGM-based treatment can be associated with a better clinical outcome than no treatment or other alternative treatment. However, more randomized control trials are warranted to confirm our findings and investigate the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at risk for breakthrough or severe SARS-CoV-2 infection.
Publisher: MDPI AG
Date: 29-04-2021
Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.
Publisher: MDPI AG
Date: 25-06-2021
DOI: 10.3390/PATHOGENS10070809
Abstract: Background: Coinfection with bacteria, fungi, and respiratory viruses in SARS-CoV-2 is of particular importance due to the possibility of increased morbidity and mortality. In this meta-analysis, we calculated the prevalence of such coinfections. Methods: Electronic databases were searched from 1 December 2019 to 31 March 2021. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Results: Of the 6189 papers that were identified, 72 articles were included in the systematic review (40 case series and 32 cohort studies) and 68 articles (38 case series and 30 cohort studies) were included in the meta-analysis. Of the 31,953 SARS-CoV-2 patients included in the meta-analysis, the overall pooled proportion who had a laboratory-confirmed bacterial infection was 15.9% (95% CI 13.6–18.2, n = 1940, 49 studies, I2 = 99%, p 0.00001), while 3.7% (95% CI 2.6–4.8, n = 177, 16 studies, I2 = 93%, p 0.00001) had fungal infections and 6.6% (95% CI 5.5–7.6, n = 737, 44 studies, I2 = 96%, p 0.00001) had other respiratory viruses. SARS-CoV-2 patients in the ICU had higher co-infections compared to ICU and non-ICU patients as follows: bacterial (22.2%, 95% CI 16.1–28.4, I2 = 88% versus 14.8%, 95% CI 12.4–17.3, I2 = 99%), and fungal (9.6%, 95% CI 6.8–12.4, I2 = 74% versus 2.7%, 95% CI 0.0–3.8, I2 = 95%) however, there was an identical other respiratory viral co-infection proportion between all SARS-CoV-2 patients [(ICU and non-ICU) and the ICU only] (6.6%, 95% CI 0.0–11.3, I2 = 58% versus 6.6%, 95% CI 5.5–7.7, I2 = 96%). Funnel plots for possible publication bias for the pooled effect sizes of the prevalence of coinfections was asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry (p values 0.05). Conclusion: Bacterial co-infection is relatively high in hospitalized patients with SARS-CoV-2, with little evidence of S. aureus playing a major role. Knowledge of the prevalence and type of co-infections in SARS-CoV-2 patients may have diagnostic and management implications.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for SAAD ALHUMAID.