Klebsiella species cause infections at multiple sites, including lung, urinary tract, bloodstream, wound or surgical site, and brain. These infections are more likely to occur in people with preexisting health conditions. Klebsiella pneumoniae (K. pneumoniae) has emerged as a major pathogen of international concern due to the increasing incidences of hypervirulent and carbapenem-resistant strains. It is imperative to understand risk factors, prevention strategies, and therapeutic avenues to treat multidrug-resistant Klebsiella infections. Here, we highlight the epidemiology, risk factors, and control strategies against K. pneumoniae infections to highlight the grave risk posed by this pathogen and currently available options to treat Klebsiella-associated diseases.

Coronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that more severe cases have a late-onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the late onset of antibody response as a risk factor for disease severity, however, there is a limited role of antibody titers in predicting disease severity of COVID-19.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease, and its morbidity and mortality are increasing. There are many studies that have tried to explain the pathogenesis of COPD from genetic susceptibility, to identify the susceptibility of COPD factors, which play a role in early prevention, early detection and the early treatment. However, it is well known that COPD is an inflammatory disease characterized by incomplete reversible airflow limitation in which genes interact with the environment. In recent years, many studies have proved gene polymorphisms and COPD correlation. However, there is less research on the relationship between COPD and genome-wide association study (GWAS), epigenetics and apoptosis. In this paper, we summarized the correlation between gene level and COPD from the following four aspects: the GWAS, the gene polymorphism, the epigenetics and the apoptosis, and the relationship between COPD and gene is summarized comprehensively.

Background: Disease severity in COVID-19 ranges from asymptomatic infection to severe disease and death, especially in older subjects. The risk for severe infection and death has been reported to be 2X in those between 30 and 40 years, 3X in those between 40 and 50 years, and 4X in those between 50 and 65 years, compared to the reference group of 18– 29 years. Objective: To investigate the early changes in host immune responses that are altered with age and the difference in the early host inflammatory response that dictates a symptomatic versus asymptomatic course of COVID-19. Patients and Methods: COVID-19 subjects were identified by screening at the airport upon arrival from a foreign destination to China. Patients were either asymptomatic or had a mild disease when the first oro-pharyngeal (OP) swab samples were collected. Patients were quarantined and blood and throat swabs were collected during the course of the disease, allowing identification of the earliest host response to COVID-19. These patients were followed until their OP sample turned COVID-19 negative. Results: Data were obtained from 126 PCR-confirmed COVID-19 patients. The blood samples were obtained within 48 days of qPCR confirmation of viral infection. Older subjects (> 30 years) had significantly elevated levels of anti-inflammatory cytokine IL-10, a significant decrease in the percentage of CD8+ T cells, and expansion in NKT cell fraction. This was associated with significantly elevated viral load and a delayed humoral response in older subjects. Compared to symptomatic subjects, asymptomatic patients had an early increase in pro-inflammatory cytokine IL-2, while a decrease in both T regulatory cells and anti-inflammatory cytokine IL-10. Further, asymptomatic disease was associated with early humoral response and faster viral clearance. Conclusion: Early inflammatory response potentially plays a critical role for host-defense in COVID-19. The impaired early inflammatory response was associated with older age while a robust early inflammation was associated with asymptomatic disease.

Background: SERPINA1 gene has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), while smoking is a known risk factor for COPD. Little is known on the effect of SERPINA1 gene and its interaction with smoking in the Chinese population. In this study, the effect of SERPINA1 gene polymorphisms on COPD risk and its interaction with smoking status has been investigated. Method: A total of 120 COPD patients and 481 healthy controls were recruited at The Armed Police Corps Hospital. Data on demographic variables, smoking status, history of occupational dust exposure, and allergies were collected. Genotyping for single nucleotide polymorphism’s (SNP) rs1243160, rs2854254, and rs8004738 was performed in all participants. Results: SNP rs8004738 genotype was associated with a significantly higher risk for COPD (odds ratio (OR) =1.835, 95% confidence interval (CI): 1.002–3.360), whereas SNPs rs1243160 and rs2854254 did not exhibit such an association. Smoking habit also significantly increased the risk for COPD (OR =2.306, 95% CI: 1.537–3.459). On stepwise logistic regression analysis, advanced age, smoking, and SNP rs8004738 variant were associated with increased risk for COPD, while female gender and higher educational status decreased the risk. On additive interaction analysis, a significant interactive effect of SNP rs8004738 and smoking was observed in this population (relative excess risk due to interaction =0.478; attributable proportion due to interaction (AP) =0.123; S=1.197). Conclusion: SNP rs8004738 of SERPINA1 gene significantly interacted with smoking status and was associated with a higher risk for COPD in the Chinese population.

Host response to lung infection includes coordinated efforts of multiple cell types, including the lung epithelium and macrophages. Importantly, both the lung epithelium and macrophages can internalize and clear invading pathogens. However, the mechanisms and their ability to internalize or phagocytose differ. Akt is a key cellular pathway that controls cell proliferation and survival, in addition to its role in host defense. The role of the Akt pathway was assessed using pharmacological Akt modulators in lung epithelial (A549) and macrophage (RAW 264.7) cell lines during Klebsiella bacterial infection. Our data show that the inhibition of the Akt pathway using specific Akt inhibitor MK2206 increased the phagocytic ability of lung epithelial cells but not of macrophages. In contrast, the activation of Akt using specific activator SC-79 decreased the phagocytic ability of epithelial cells, while it increased the phagocytic ability of macrophages. The altered phagocytic ability in both cell types using Akt modulators was not due to changes in bacterial adhesion to the host cell. The clinical usefulness of these Akt modulators may vary based on the type of infection and on the relative contribution of epithelial cells and macrophages in clearing the particular bacterial infection. The Akt pathway has differential roles in the internalization of Klebsiella bacteria by respiratory epithelial cells and immune cells.