COVID-19 intranasal vaccines: current progress, advantages, prospects, and challenges.

Multiple vaccines have recently been developed, and almost all the countries are presently vaccinating their population to tackle the COVID-19 pandemic. Most of the COVID-19 vaccines in use are administered via intramuscular (IM) injection, eliciting protective humor and cellular immunity. COVID-19 intranasal (IN) vaccines are also being developed that have shown promising ability to induce a significant amount of antibody-mediated immune response and a robust cell-mediated immunity as well as hold the added ability to stimulate protective mucosal immunity along with the additional advantage of the ease of administration as compared to IM injected vaccines. By inducing secretory IgA antibody responses specifically in the nasal compartment, the intranasal SARS-CoV-2 vaccine can prevent virus infection, replication, shedding, and disease development, as well as possibly limits virus transmission. This article highlights the current progress, advantages, prospects, and challenges in developing intranasal COVID-19 vaccines for countering the ongoing pandemic.

Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders - Advances and challenges.

Autoimmune diseases are caused when immune cells act against self-protein. This biological self-non-self-discrimination phenomenon is controlled by a distinct group of lymphocytes known as regulatory T cells (Tregs), which are key inflammatory response regulators and play a pivotal role in immune tolerance and homeostasis. Treg-mediated robust immunosuppression provides self-tolerance and protection against autoimmune diseases. However, once this system fails to operate or poorly operate, it leads to an extreme situation where immune system reacts against self-antigens and destroys host organs, thus causing autoimmune diseases. Tregs can target both innate and adaptive immunity via modulating multiple immune cells such as neutrophils, monocytes, antigen-presenting cells, B cells, and T cells. This review highlights the Treg-mediated immunosuppression, role of several markers and their interplay during Treg development and differentiation, and advances in therapeutic aspects of Treg cells to reduce severity of autoimmunity-related conditions along with emphasizing limitations and challenges of their usages.

Prophylactic and therapeutic insights into trained immunity: A renewed concept of innate immune memory.

Trained immunity is a renewed concept of innate immune memory that facilitates the innate immune system to have the capacity to remember and train cells via metabolic and transcriptional events to enable them to provide nonspecific defense against the subsequent encounters with a range of pathogens and acquire a quicker and more robust immune response, but different from the adaptive immune memory. Reversing the epigenetic changes or targeting the immunological pathways may be considered potential therapeutic approaches to counteract the hyper-responsive or hypo-responsive state of trained immunity. The efficient regulation of immune homeostasis and promotion or inhibition of immune responses is required for a balanced response. Trained immunity-based vaccines can serve as potent immune stimuli and help in the clearance of pathogens in the body through multiple or heterologous effects and confer protection against nonspecific and specific pathogens. This review highlights various features of trained immunity and its applications in developing novel therapeutics and vaccines, along with certain detrimental effects, challenges as well as future perspectives.

Five-year resistance trends in pathogens causing healthcare-associated infections at a multi-hospital healthcare system in Saudi Arabia, 2015-2019.

OBJECTIVES: Awareness of antimicrobial resistance (AMR) patterns in a given healthcare setting is important to inform the selection of appropriate antimicrobial therapy to reduce the further rise and spread of AMR as well as the rate of healthcare-associated infections (HAIs) and multidrug-resistant (MDR) organisms. We aimed to describe resistance patterns to several antimicrobial agents in pathogens causing HAIs isolated from patients using data gathered at three private tertiary-care hospitals in Saudi Arabia. METHODS: Data on trends in AMR among bacteria causing HAIs and MDR events in children and adults at three private hospitals were collected retrospectively (2015-2019) using surveillance data. RESULTS: Over the 5-year period, 29 393 pathogens caused 17 539 HAIs in 15 259 patients. Approximately 57.3% of patients were female and the mean age was 38.4 ± 16.8 years (81.4% adults, 18.6% children). Gram-negative pathogens were four times more likely to cause HAIs compared with Gram-positive bacteria (79.3% vs. 20.7%). Ranking of causative pathogens in decreasing order was Escherichia coli (42.2%), Klebsiella spp. (16.8%) and Staphylococcus aureus (13.9%). Acinetobacter spp. were the only pathogens to decrease significantly (7% reduction; P = 0.033). The most common resistant pathogens were extended-spectrum cephalosporin-resistant E. coli (37.1%), extended-spectrum cephalosporin-resistant Klebsiella (27.8%), carbapenem-non-susceptible Acinetobacter spp. (19.5%), carbapenem-non-susceptible Pseudomonas aeruginosa (19.2%) and methicillin-resistant S. aureus (18.6%). CONCLUSION: National collaboration is required by prompt feedback to local authorities to tackle regional differences in AMR. This can help plan timely containment interventions to stop and contain microbial threats and swiftly assess their impact.

Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis.

(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.