Infection, cases due to SARS-CoV-2 in rural areas during early COVID-19 vaccination: findings from serosurvey study in a rural cohort of eastern India.

COVID-19 serosurvey provides a better estimation of people who have developed antibody against the infection. But limited information on such serosurveys in rural areas poses many hurdles to understand the epidemiology of the virus and to implement proper control strategies. This study was carried out in the rural catchment area of Model Rural Health Research Unit in Odisha, India during March-April 2021, the initial phase of COVID vaccination. A total of 60 village clusters from four study blocks were identified using probability proportionate to size sampling. From each cluster, 60 households and one eligible participant from each household (60 per cluster) were selected for the collection of blood sample and socio-demographic data. The presence of SARS-CoV-2 antibody was tested using the Elecsys Anti-SARS-CoV-2 immunoassay. The overall seroprevalence after adjusting for test performance was 54.21% with an infection to case ratio of 96.89 along with 4.25% partial and 6.79% full immunisation coverage. Highest seroprevalence was observed in the age group of 19-44 years and females had both higher seroprevalence as well as vaccine coverage. People of other backward caste also had higher seropositivity than other caste categories. The study emphasises on continuing surveillance for COVID-19 cases and prioritizing COVID-19 vaccination for susceptible groups for better disease management.

Association of quorum sensing and biofilm formation with Salmonella virulence: story beyond gathering and cross-talk.

Enteric fever (typhoid and paratyphoid fever) is a public health concern which contributes to mortality and morbidity all around the globe. It is caused mainly due to ingestion of contaminated food and water with a gram negative, rod-shaped, flagellated bacterium known as Salmonella enterica serotype typhi (typhoid fever) or paratyphi (paratyphoid fever). Clinical problems associated with Salmonellosis are mainly bacteraemia, gastroenteritis and enteric fever. The bacteria undergo various mechanisms to escape itself from immune reaction of the host, modulating immune response at the site of infection leading to virulence factor production and anti-microbial resistance. Biofilm is one of the adaptation mechanisms through which Salmonella survives in unfavourable conditions and thus is considered as a major threat to public health. Another property of the bacteria is "Quorum Sensing", which is a cell-cell communication and most of the pathogenic bacteria use it to coordinate the production of several virulence factors and other behaviours such as swarming and biofilm formation. Earlier, quorum sensing was believed to be just a medium for communication but, later on, its role in virulence has been studied. However, there are negligible information relating to interaction between quorum sensing and biofilm formation and how these events play crucial role in Salmonella pathogenesis. The review is a summary of updated information regarding how Salmonella uses these properties to spread more and survive better, making a challenge for clinicians and public health experts. Therefore, this review would help bring an insight regarding how biofilm formation and quorum sensing are inter-related and their role in pathogenesis and virulence of Salmonella.

Antimicrobial Resistance and Biofilm Formation of Staphylococcus aureus Isolates from Febrile Cases: Findings from a Rural Cohort of Odisha, India.

This study investigated the major pathogens in fever patients' blood in a rural cohort and characterized its virulence. A total of 718 blood samples received from IPD/OPD (inpatient department/outpatient department) patients with H/O (history of) fever were cultured, and 73 out of 83 culture-positive samples were identified as Staphylococcus aureus. The isolates showed higher resistance to penicillin, most being multidrug resistant. They formed biofilm in vitro, and 27.4% of the isolates were strong biofilm producers. They were sensitive towards linezolid, gentamicin, and tetracycline. The findings emphasize the necessity of preventing and managing staphylococcal infection and regular antimicrobial surveillance in rural areas.

Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutant receptor-binding domain with ACE2.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the whole world, including Odisha, a state in eastern India. Many people have migrated to the state from different countries as well as other states during this SARS-CoV-2 pandemic. The aim of this study was to analyse the receptor-binding domain (RBD) sequence of the spike protein from isolates collected from throat swab samples of COVID-19-positive patients and further to assess the RBD affinity for angiotensin-converting enzyme 2 (ACE2) of different species, including humans. METHODS: Whole-genome sequencing for 35 clinical SARS-CoV-2 isolates from COVID-19-positive patients was performed by ARTIC amplicon-based sequencing. Sequence analysis and phylogenetic analysis were performed for the spike region and the RBD region of all isolates. The interaction between the RBD and ACE2 of five different species was also analysed. RESULTS: The spike region of 32 isolates showed one or multiple alterations in nucleotide bases in comparison with the Wuhan reference strain. One of the identified mutations, at position 1204 (Ref A, RMRC 22 C), in the RBD coding region of the spike protein showed stronger binding affinity for human ACE2. Furthermore, RBDs of all the Indian isolates showed binding affinity for ACE2 of different species. CONCLUSION: As mutant RBD showed stronger interaction with human ACE2, it could potentially result in higher infectivity. The binding affinity of the RBDs for ACE2 of all five species studied suggests that the virus can infect a wide variety of animals, which could also act as natural reservoir for SARS-CoV-2.

Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis.

Purpose: Nearly a third to half of patients with noninfectious uveitis (NIU) fail to achieve control with immunomodulatory therapy (IMT). Multidrug resistance (MDR) proteins are transmembrane proteins that allow efflux of intracellular drugs, leading to drug resistance. The aim of our study was to compare MDR protein function in blood CD4+ cells between responders and nonresponders to IMT. Methods: We included NIU patients on IMT for ≥6 months and corticosteroid dose ≤10 mg/d. Nonresponders to treatment were those with worsening (two or more steps) of inflammation in the past 3 months on full-dose immunosuppressive therapy. MDR function was assessed by Rhodamine-123 dye retention in blood CD4+ cells. Three nonresponders were treated with adjunctive oral cyclosporine A (CSA, MDR inhibitor) therapy for 2 months and reevaluated. Results: Fourteen NIU patients were recruited. Most (n = 8) had Vogt-Koyanagi-Harada disease. These included nine nonresponders and five responders to IMT. Nonresponders produced significantly higher MDR function and proinflammatory cytokines (interferon γ, tumor necrosis factor α, interleukin 17, and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)) than responders. In vitro CSA treatment of CD4+ cells inhibited MDR expression and proinflammatory cytokine production while increasing Foxp3. Finally, adjunctive oral CSA therapy led to improvement in clinical inflammatory scores with a concurrent decrease in MDR function and proinflammatory cytokine secretion. Conclusions: MDR function is significantly higher in CD4+ T cells of nonresponders to IMT. Adjunctive CSA therapy may decrease MDR function and allow improvement in treatment response to IMT. Translational Relevance: Our study highlights the need for MDR inhibition strategies in NIU patients not responding to IMT for improving the efficacy of anti-inflammatory therapy.

Cysteine mediated disulfide bond formation in RAGE V domain facilitates its functionally relevant dimerization.

Receptor for Advanced Glycation End product (RAGE) is a multiligand receptor implicated in diverse pathological conditions such as diabetes, atherosclerosis, cancer and neural diseases. Extracellular, RAGE consists of V, C1 and C2 domains. Here, we show RAGE exists as a monomer in equilibrium with a fraction of a covalently linked dimer of monomers via its V domain through cysteine. In order to understand the functional implication of this dimer, we examined the binding capacity and functional potential of RAGE dimer via advanced glycation end products (AGEs) which shows enhanced binding capacity towards V domain, ERK phosphorylation, cytokine release and actin polymerization ability of the dimeric form for AGEs compared with the reduced monomeric form. Our data, suggests that the dimeric state of RAGE controls its function and ligand mediated signaling which may play important role in RAGE mediated various diseases.