Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines.

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells' exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

Antibiotic Based Phenotype and Hospital Admission Profile are the Most Likely Predictors of Genotyping Classification of MRSA.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is associated with increased morbidity, mortality, and financial burdens. Phenotyping methods are used to classify MRSA as either health care MRSA (HA-MRSA) or community-associated MRSA (CA-MRSA). Recent studies suggested the phenotyping methods are not always reliable, based on a lack of concordance with genotyping results. OBJECTIVE: In this study, concordance of classification methods based on clinical characteristics or antibiotic susceptibility compared to the gold standard genotyping was assessed in the classification of MRSA. METHODS: We compared the genotypes and phenotypes of MRSA in 133 samples taken from patients in Saudi Arabia. Statistical analyses included concordance, specificity and sensitivity, and logistic regression modeling. RESULTS: There was fair a definite agreement between the health care risk and infection type methods (p < .001), but no statistically significant agreement between the susceptibility pattern and health care risk methods (p = 243), and between susceptibility pattern and infection type methods (p = .919). Reduced multiple regression modelling suggested the potential of a phenotyping-based method of antibiotic susceptibility pattern (OR = 15.47, p < .001) in conjunction with hospital admission profile(OR = 2.87, p = .008) to accurately identify MRSA as HA-MRSA and CA-MRSA. CONCLUSION: The use of a standardized phenotyping technique, using susceptibility pattern and hospital admission profiles to classify MRSA infections as either HA-MRSA or CA-MRSA, would facilitate diagnosis, infection control efforts, prevention, and assignment of appropriate therapies. The ability to use phenotyping in the classification of these strains would improve efforts to contend with this adept and evolving bacterial organism.

Direct identification and susceptibility testing of positive blood cultures using high speed cold centrifugation and Vitek II system.

Compared to routine isolated colony-based methods, direct testing of bacterial pellets from positive blood cultures reduces turnaround time for reporting of antibiotic susceptibility. The aim of this study was to compare the accuracy, and precision, of a rapid method for direct identification and susceptibility testing of blood cultures with the routine method used in our laboratory, using Vitek 2. A total of 60 isolates were evaluated using the candidate and the routine method. The candidate method had 100% accuracy for the identification of Gram negative bacteria, Staphylococcus and Enterococcus, 50% for Streptococcus and 33.3% for Corynebacterium species. Susceptibility testing of Gram negative isolates yielded 98-100% essential agreement. For Staphylococcus and Enterococcus isolates, essential agreement was 100% for 17 antibiotics except for moxifloxacin. Direct testing of blood culture samples with Vitek 2 produced reliable identification and susceptibility results 18-24h sooner for aerobic/anaerobic facultative Gram-negative bacteria and Gram-positive Staphylococcus and Enterococcus strains.

Comparison among four proposed direct blood culture microbial identification methods using MALDI-TOF MS.

Matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry facilitates rapid and accurate identification of pathogens, which is critical for sepsis patients. In this study, we assessed the accuracy in identification of both Gram-negative and Gram-positive bacteria, except for Streptococcus viridans, using four rapid blood culture methods with Vitek MALDI-TOF-MS. We compared our proposed lysis centrifugation followed by washing and 30% acetic acid treatment method (method 2) with two other lysis centrifugation methods (washing and 30% formic acid treatment (method 1); 100% ethanol treatment (method 3)), and picking colonies from 90 to 180min subculture plates (method 4). Methods 1 and 2 identified all organisms down to species level with 100% accuracy, except for Streptococcus viridans, Streptococcus pyogenes, Enterobacter cloacae and Proteus vulgaris. The latter two were identified to genus level with 100% accuracy. Each method exhibited excellent accuracy and precision in terms of identification to genus level with certain limitations.

Prevalence of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus infections in a Saudi Arabian hospital.

Panton-Valentine leukocidin (PVL) is a two-component toxin associated with the toxicity and virulence of Staphylococcus aureus. The presence of PVL is well documented in community-acquired methicillin-resistant S. aureus (CA-MRSA) and is observed in methicillin-susceptible S. aureus (MSSA) with variable prevalence. We assessed the prevalence of PVL in a sample of 93 MSSA patients in a healthcare facility in Eastern Saudi Arabia using real-time PCR for lukSF-PV genes. The presence or absence of PVL was correlated with age, gender, hospitalization status, infection site and antibiotic resistance. PVL was detected in 28 (30%) patient samples. PVL was associated with a greater likelihood of resistance to trimethoprim-sulfamethoxazole (a resistance of 39.2% of PVL-positive isolates compared to 6.1% of PVL-negative isolates) (p < 0.0007). These results suggest a significant prevalence of PVL expression in MSSA strains in the study population and call for monitoring of and surveillance programs for PVL status and the selection of appropriate antibiotic treatments.