Assessment of Urinary Biomarkers for Infectious Diseases Using Lateral Flow Assays: A Comprehensive Overview.

Screening of biomarkers is a powerful approach for providing a holistic view of the disease spectrum and facilitating the diagnosis and prognosis of the state of infectious diseases. Unaffected by the homeostasis mechanism in the human body, urine accommodates systemic changes and reflects the pathophysiological condition of an individual. Easy availability in large volumes and non-invasive sample collection have rendered urine an ideal source of biomarkers for various diseases. Infectious diseases may be communicable, and therefore early diagnosis and treatment are of immense importance. Current diagnostic approaches preclude the timely identification of clinical conditions and also lack portability. Point-of-care (POC) testing solutions have gained attention as alternative diagnostic measures due to their ability to provide rapid and on-site results. Lateral flow assays (LFAs) are the mainstay in POC device development and have attracted interest owing to their potential to provide instantaneous results in resource-limited settings. The discovery and optimization of a definitive biomarker can render POC testing an excellent platform, thus impacting unwarranted antibiotic administration and preventing the spread of infectious diseases. This Review summarizes the importance of urine as an emerging biological fluid in infectious disease research and diagnosis in clinical settings. We review the academic research related to LFAs. Further, we also describe commercial POC devices based on the identification of urinary biomarkers as diagnostic targets for infectious diseases. We also discuss the future use of LFAs in developing more effective POC tests for urinary biomarkers of various infections.

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.

Emergence, Transmission, and Potential Therapeutic Targets for the COVID-19 Pandemic Associated with the SARS-CoV-2.

The pandemic of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 at the end of 2019 marked the third outbreak of a highly pathogenic coronavirus affecting the human population in the past twenty years. Cross-species zoonotic transmission of SARS-CoV-2 has caused severe pathogenicity and led to more than 655,000 fatalities worldwide until July 28, 2020. Outbursts of this virus underlined the importance of controlling infectious pathogens across international frontiers. Unfortunately, there is currently no clinically approved antiviral drug or vaccine against SARS-CoV-2, although several broad-spectrum antiviral drugs targeting multiple RNA viruses have shown a positive response and improved recovery in patients. In this review, we compile our current knowledge of the emergence, transmission, and pathogenesis of SARS-CoV-2 and explore several features of SARS-CoV-2. We emphasize the current therapeutic approaches used to treat infected patients. We also highlight the results of in vitro and in vivo data from several studies, which have broadened our knowledge of potential drug candidates for the successful treatment of patients infected with and discuss possible virus and host-based treatment options against SARS-CoV-2.