The Escherichia coli that produces extended-spectrum lactamases (ESBL-E. coli) can develop resistance to many antibiotics. The control of ESBL-E. coli disorders is challenging due to their restricted therapeutic approaches, so this study aims to determine the prevalence and pattern of the antibiotic resistance of ESBL-E. coli among male and female patients with urinary tract infections in Riyadh, Saudi Arabia. During the period of 2019 to 2020 at King Fahd Medical City, Riyadh, 2250 urine samples from patients with urinary tract infections (UTIs) were collected, and microbial species were cultured and identified using standard biochemical techniques. A double-disc synergy test was used to identify ESBL-producing strains of E. coli, and an in vitro method and the clinical laboratory standard institute (CLSI) criteria were employed to determine the resistance of these strains to antimicrobial drugs. ESBL-E. coli was detected in 510 (33.49%) of the 1523 E. coli isolates, 67.27% of which were recovered from women and 33.7% of which were recovered from men. A total of 284 (55.69%) ESBL-E. coli isolates were found in patients under 50 years of age, and 226 (44.31%) were found in patients over 50 years of age. Nearly all the isolates of ESBL-E. coli were resistant to cephalosporins (ceftriaxone, cefotaxime, cefepime, cefuroxime, and cephalothin) and penicillin (ampicillin), whereas the majority of the isolates were sensitive to several carbapenems (imipenem, meropenem, and ertapenem), aminoglycosides (amikacin), and nitrofurantoins. The development of antibiotic resistance by ESBL-E. coli, the most frequent pathogen linked to urinary tract infections, plays a crucial role in determining which antibiotic therapy is appropriate.

Graphical abstract The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01061-z.

In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019–2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.

Background Rhinoviruses (RVs) are the most frequent cause of community acquired pneumonia in children and the major cause of exacerbations of chronic obstructive pulmonary disease, leading to substantial morbidity, mortality and hospital admission. The spectrum of RV serotypes in circulation, their genetic variability and immune responses could be implicated in the etiology of disease severity. During rhinovirus infection, both antiviral immunity and pro-inflammatory responses play a critical role in the clearance of the virus. A variation in these responses leads to deficient clearing of the virus and sustained inflammation. Materials and methods The study specimens were obtained from pediatric pneumonia patients (n = 374) attending the outpatient department (OPD) or admitted to the intensive care unit (ICU) at King Fahad Medical City. All patient’ samples testing positive for rhinovirus (n = 102) by conventional nested reverse transcription PCR (RT-PCR) assay were used for genetic sequencing by Sanger sequencing and phylogenetic analyses. The clinical datasets used and analyzed during the current study are available from the corresponding author on request. Results We investigated 374 children with pneumonia and RV was detected in 27% with radiological evidence of consolidation and ground glass opacities in the lung. Genetic sequencing and homology 3D modeling revealed changes at amino terminal of conserved Viral Protein 4 (VP4) epitope in RV-A101 serotype especially serine at several positions that is important for interactive binding with the host immune cells. We found dysregulation of pulmonary gene expression of Th1- and Th2 cytokines and chemokines in RV-A 101 and RV-C 8 associated pneumonia patients, and found that 29 genes were overexpressed. IFN-γ (Interferon gamma) and IL-18 (Interleukin or interferon-gamma-inducing factor) mRNA expression levels were significantly upregulated in the RV-A101-associated pneumonia patients. Conclusion This study provided evidence of mutations at the amino terminal of the conserved VP4 epitope that could shape the immune response as well as affect the cross neutralizing capacity of the conserved epitopes, thus helping RVs escape the immune responses. Further functional studies are needed to determine any changes in the cross serotype virus neutralization ability for vaccine development.

The complement system represents an innate immune response consisting of a protein network. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement‐modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including Seven complement proteins including complement regulatory factors during MERS-CoV infection. We also measured the expression of lung neutrophil chemoattractant chemokine IL-8 (CXCL8) and RANTES (CCL5). Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a and C3a, was positively correlated with IL-8, RANTES and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P (properdin), suggesting positive regulation of the complement during MERS-CoV infection. In addition, we also demonstrated that a high viral load in all patients with MERS-CoV correlated with C5a and C3a levels. Pulmonary complement mediators, disease severity, and an increased fatality rate may be linked to the degree of complement activation against MERS-CoV. High levels of lung C5a, C3a, factor P, IL-8 and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8 and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the functional partners (protiens) prediction of highly expressed proteins (C5a, C3a, factor P, IL-8 and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.