Targeting Specific Checkpoints in the Management of SARS-CoV-2 Induced Cytokine Storm.

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.

Targeting Specific Checkpoints in the Management of SARS-CoV-2 Induced Cytokine Storm

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.

Should samples be weighted to decrease selection bias in online surveys during the COVID-19 pandemic? Data from seven datasets.

BACKGROUND: Online surveys have triggered a heated debate regarding their scientific validity. Many authors have adopted weighting methods to enhance the quality of online survey findings, while others did not find an advantage for this method. This work aims to compare weighted and unweighted association measures after adjustment over potential confounding, taking into account dataset properties such as the initial gap between the population and the selected sample, the sample size, and the variable types. METHODS: This study assessed seven datasets collected between 2019 and 2021 during the COVID-19 pandemic through online cross-sectional surveys using the snowball sampling technique. Weighting methods were applied to adjust the online sample over sociodemographic features of the target population. RESULTS: Despite varying age and gender gaps between weighted and unweighted samples, strong similarities were found for dependent and independent variables. When applied on the same datasets, the regression analysis results showed a high relative difference between methods for some variables, while a low difference was found for others. In terms of absolute impact, the highest impact on the association measure was related to the sample size, followed by the age gap, the gender gap, and finally, the significance of the association between weighted age and the dependent variable. CONCLUSION: The results of this analysis of online surveys indicate that weighting methods should be used cautiously, as weighting did not affect the results in some databases, while it did in others. Further research is necessary to define situations in which weighting would be beneficial.

Antibiotic Discovery and Resistance: The Chase and the Race.

The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility.

Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.

Convalescent Plasma Therapy for Management of COVID-19: Perspectives and Deployment in the Current Global Pandemic.

The world is striving against the severe crisis of the COVID-19 pandemic. Healthcare professionals are struggling to treat their patients based on nonspecific therapies. Amidst this uncertainty, convalescent plasma therapy (CPT) has appeared to be an interim adjuvant therapy for severely ill patients of COVID-19 until long-term clinical trial treatment options are available. Considering the transfusion-related hazards, especially lung injuries and microbial transmission, where sensitivity is not ensured, rigorous trials should be conducted to determine this therapy's efficacy. Moreover, the ratio of recovered cases to plasma donors is not satisfying, which questioning this therapy's availability and accessibility. Although some countries are making the treatment free, the attributable cost mandates a justification for its suitability and sustainability. Our article aimed to review the published facts and findings of CPT's effectiveness in lowering the mortality rate of COVID-19. This pandemic showed that healthcare systems worldwide need core reform. A unified global collaboration must align and coordinate to face the current pandemic and enhance world readiness for future outbreaks based on health equity and equality.

The Double Burden of the COVID-19 Pandemic and Polypharmacy on Geriatric Population - Public Health Implications.

COVID-19 pandemic is inducing acute respiratory distress syndrome, multi-organ failure, and eventual death. Respiratory failure is the leading cause of mortality in the elderly population with pre-existing medical conditions. This group is particularly vulnerable to infections due to a declined immune system, comorbidities, geriatric syndrome, and potentially inappropriate polypharmacy. These conditions make the elderly population more susceptible to the harmful effects of medications and the deleterious consequences of infections, including MERS-CoV, SARS-CoV, and SARS-CoV-2. Chronic diseases among elderlies, including respiratory diseases, hypertension, diabetes, and coronary heart diseases, present a significant challenge for healthcare professionals. To comply with the clinical guidelines, the practitioner may prescribe a complex medication regimen that adds up to the burden of pre-existing treatment, potentially inducing adverse drug reactions and leading to harmful side-effects. Consequently, the geriatric population is at increased risk of falls, frailty, and dependence that enhances their susceptibility to morbidity and mortality due to SARS-CoV-2 respiratory syndrome, particularly interstitial pneumonia. The major challenge resides in the detection of infection that may present as atypical manifestations in this age group. Healthy aging can be possible with adequate preventive measures and appropriate medication regimen and follow-up. Adherence to the guidelines and recommendations of WHO, CDC, and other national/regional/international agencies can reduce the risks of SARS-CoV-2 infection. Better training programs are needed to enhance the skill of health care professionals and patient's caregivers. This review explains the public health implications associated with polypharmacy on the geriatric population with pre-existing co-morbidities during the COVID-19 pandemic.