Ancestral allele of DNA polymerase gamma modifies antiviral tolerance.

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1-4. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5. Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms5, indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals6 demonstrates enrichment of immunodeficient traits in carriers of the POLG1 p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.

Immunopathology of herpes simplex virus-associated neuroinflammation: Unveiling the mysteries.

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology-induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV-associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections.

Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Allergic contact dermatitis to lip care cosmetic products - a systematic review.

Aim: Lip care cosmetics products are any external preparation used by people to prevent drying, chapping, dullness, and beautification of lips. This study aimed to review the literature on allergic reactions induced by different types of lip care cosmetic products. Methods: A literature search was performed in PubMed from inception to June 2022. The study included articles published in English and available in full text. References of illegible articles were searched. Studies describing any patient who developed allergic contact dermatitis after the application of lip care cosmetic products were included. Results: A total of 47 reports consisting of 58 individuals experienced allergic reactions to lip care products. Several lip care cosmetics products, such as lipsticks, lip balms, lip salve, lip gloss, lip liner, and lip plumper, were found to be associated with allergic reactions. The most common ingredients that caused the allergic contact dermatitis were castor oil, benzophenone-3, gallate, wax, and colophony. Conclusions: Lip care cosmetics products contain several components that have been associated with allergic reactions. Awareness needs to be created among the general public and dermatologists regarding the presence of possible allergens in lip care cosmetic products.

Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1ß, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

Emerging Targets for Modulation of Immune Response and Inflammation in Stroke.

The inflammatory and immunological responses play a significant role after stroke. The innate immune activation stimulated by microglia during stroke results in the migration of macrophages and lymphocytes into the brain and are responsible for tissue damage. The immune response and inflammation following stroke have no defined targets, and the intricacies of the immunological and inflammatory processes are only partially understood. Innate immune cells enter the brain and meninges during the acute phase, which can cause ischemia damage. Activation of systemic immunity is caused by danger signals sent into the bloodstream by injured brain cells, which is followed by a significant immunodepression that encourages life-threatening infections. Neuropsychiatric sequelae, a major source of post-stroke morbidity, may be induced by an adaptive immune response that is initiated by antigen presentation during the chronic period and is directed against the brain. Thus, the current review discusses the role of immune response and inflammation in stroke pathogenesis, their role in the progression of injury during the stroke, and the emerging targets for the modulation of the mechanism of immune response and inflammation that may have possible therapeutic benefits against stroke.

Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases.

Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.

From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders.

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.

Targeting inflammation: a potential approach for the treatment of depression.

Major depressive disorder (MDD) or Depression is one of the serious neuropsychiatric disorders affecting over 280 million people worldwide. It is 4th important cause of disability, poor quality of life, and economic burden. Women are more affected with the depression as compared to men and severe depression can lead to suicide. Most of the antidepressants predominantly work through the modulation on the availability of monoaminergic neurotransmitter (NTs) levels in the synapse. Current antidepressants have limited efficacy and tolerability. Moreover, treatment resistant depression (TRD) is one of the main causes for failure of standard marketed antidepressants. Recently, inflammation has also emerged as a crucial factor in pathological progression of depression. Proinflammatory cytokine levels are increased in depressive patients. Antidepressant treatment may attenuate depression via modulation of pathways of inflammation, transformation in structure of brain, and synaptic plasticity. Hence, targeting inflammation may be emerged as an effective approach for the treatment of depression. The present review article will focus on the preclinical and clinical studies that targets inflammation. In addition, it also concentrates on the therapeutic approaches' that targets depression via influence on the inflammatory signaling pathways. Graphical abstract demonstrate the role of various factors in the progression and neuroinflammation, oxidative stress. It also exhibits the association of neuroinflammation, oxidative stress with depression.

Synergism of CD28 Immune Molecule in Late Immunosuppressive Phase of COVID-19: Effectiveness in Vaccinated Individuals.

Context: Lymphopenia has been frequently documented and linked to coronavirus disease 2019 (COVID-19) in a severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) attack. A decrease in the T-lymphocyte count has shown promise as a clinical indicator and predictor of COVID-19 severity. Objective: The review intended to examine the relationship of COVID-19 infections in individuals to lost expression of CD28 on naive CD4+/CD8+-mediated, vaccine-specific, neutralizing antibody responses. Design: The research team performed a narrative review by searching eight databases: Medline, Elsevier, Cochrane, PubMed, Google Scholar, Mendeley, and Springer Nature. The search used the following key terms: SARS CoV-2, clinical aspects and pathology of SARS CoV-2, involvement of viral spike (S) protein in SARS CoV-2, immunological changes in COVID-19 infection, basic overview of CD28 immuno-molecule ligand, reduction of vaccine therapeutic efficacy in COVID-19 infection, and immunomodulatory response of lost CD28 ligand. Setting: This study was done in a Maharishi Arvind College of Pharmacy, Jaipur, India. Results: In COVID-19 patients, particularly those with severe disease, had increased levels of IL-2 or IL-2R. Given IL-2's supportive role in the expansion and differentiation of T cells, the authors exhibiting that lymphopenia, particularly in severe COVID-19, could be attributed to nonfunctional and dysfunctional differentiation of CD4+ and CD8+ T cells as a result of low CD28 immuno-molecule expression on naive T cells. Conclusions: The literature review found that independent, early immunological prognostic markers for a poor prognosis, in addition to higher levels of IL-6, include a substantial proportion of large inflammatory monocytes and a small proportion of chronic CD28+ CD4+T cells. The current findings suggest that a combination of COVID-19 vaccination with SARS CoV-2-reactive naive T cells with the CD28 immune-molecule may be a viable method for establishing T-cell-based, adaptive cellular immunotherapy against COVID-19 infection. Further research is needed, especially larger studies to confirm the current findings, to improve early clinical treatment.

Folic Acid Functionalized Diallyl Trisulfide-Solid Lipid Nanoparticles for Targeting Triple Negative Breast Cancer.

DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against triple-negative breast cancer (TNBC). Its hydrophobicity, short half-life, lack of target selectivity, and limited bioavailability at the tumor site limit its efficacy in treating TNBC. Overexpression of the Folate receptor on the surface of TNBC is a well-known target receptor for overcoming off-targeting, and lipid nanoparticles solve the limitations of limited bioavailability and short half-life. In order to overcome these constraints, we developed folic acid (FA)-conjugated DATS-SLNs in this research. The design of experiment (DoE) method was employed to optimize the FA-DATS-SLNs' nanoformulation, which resulted in a particle size of 168.2 ± 3.78 nm and a DATS entrapment of 71.91 ± 6.27%. The similarity index between MCF-7 and MDA-MB-231 cell lines demonstrates that FA-DATS-SLNs are more therapeutically efficacious in the treatment of aggravating TNBC. Higher cellular internalization and efficient Bcl2 protein downregulation support the hypothesis that functionalization of the FA on the surface of DATS-SLNs improves anticancer efficacy when compared with DATS and DATS-SLNs. FA-functionalized DATS-SLNs have demonstrated to be a promising therapeutic strategy for TNBC management.

Quality by Design (QbD) Based Method for Estimation of Xanthohumol in Bulk and Solid Lipid Nanoparticles and Validation.

The analytical quality by design (AQbD) approach is utilized for developing and validating the simple, sensitive, cost-effective reverse-phase high performance liquid chromatographic method for the estimation of xanthohumol (XH) in bulk and nanoformulations. The Box-Behnken design (BBD) is applied for method optimization. The mobile phase ratio, pH and flow rate were selected as independent variables, whereas retention time, peak area, peak height, tailing factor, and theoretical plates were selected as dependent variables. The chromatogram of XH obtained under optimized conditions has given optimum conditions such as retention time (5.392 min), peak area (1,226,737 mAU), peak height (90,121 AU), tailing factor (0.991) and theoretical plates (4446.667), which are contoured in the predicted values shown by BBD. Validation of the method has been performed according to ICH Q2(R1) recommendations, using optimized conditions for linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, precision, robustness and system suitability. All the values of validation parameters lie within the acceptable limits prescribed by ICH. Therefore, the developed and validated method of XH by the AQbD approach can be applied for the estimation of XH in bulk and various nanoformulations.

A cell competition-based small molecule screen identifies a novel compound that induces dual c-Myc depletion and p53 activation.

Breakpoint Cluster Region-Abelson kinase (BCR-Abl) is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells (LSCs), the cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. New strategies to target cancers driven by BCR-Abl are therefore urgently needed. We performed a small molecule screen based on competition between isogenic untransformed cells and BCR-Abl-transformed cells and identified several compounds that selectively impair the fitness of BCR-Abl-transformed cells. Interestingly, systems-level analysis of one of these novel compounds, DJ34, revealed that it induced depletion of c-Myc and activation of p53. DJ34-mediated c-Myc depletion occurred in a wide range of tumor cell types, including lymphoma, lung, glioblastoma, breast cancer, and several forms of leukemia, with primary LSCs being particularly sensitive to DJ34. Further analyses revealed that DJ34 interferes with c-Myc synthesis at the level of transcription, and we provide data showing that DJ34 is a DNA intercalator and topoisomerase II inhibitor. Physiologically, DJ34 induced apoptosis, cell cycle arrest, and cell differentiation. Taken together, we have identified a novel compound that dually targets c-Myc and p53 in a wide variety of cancers, and with particularly strong activity against LSCs.

Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) is a paediatric cancer driven either by fusion proteins (e.g., PAX3-FOXO1) or by mutations in key signalling molecules (e.g., RAS or FGFR4). Despite the latter providing opportunities for precision medicine approaches in RMS, there are currently no such treatments implemented in the clinic. METHODS: We evaluated biologic properties and targeting strategies for the FGFR4 V550L activating mutation in RMS559 cells, which have a high allelic fraction of this mutation and are oncogenically dependent on FGFR4 signalling. Signalling and trafficking of FGFR4 V550L were characterised by confocal microscopy and proteomics. Drug effects were determined by live-cell imaging, MTS assay, and in a mouse model. RESULTS: Among recently developed FGFR4-specific inhibitors, FGF401 inhibited FGFR4 V550L-dependent signalling and cell proliferation at low nanomolar concentrations. Two other FGFR4 inhibitors, BLU9931 and H3B6527, lacked potent activity against FGFR4 V550L. Alternate targeting strategies were identified by RMS559 phosphoproteomic analyses, demonstrating that RAS/MAPK and PI3K/AKT are essential druggable pathways downstream of FGFR4 V550L. Furthermore, we found that FGFR4 V550L is HSP90-dependent, and HSP90 inhibitors efficiently impeded RMS559 proliferation. In a RMS559 mouse xenograft model, the pan-FGFR inhibitor, LY2874455, did not efficiently inhibit growth, whereas FGF401 potently abrogated growth. CONCLUSIONS: Our results pave the way for precision medicine approaches against FGFR4 V550L-driven RMS.

Nanostructured Conductive Metal Organic Frameworks for Sustainable Low Charge Overpotentials in Li-Air Batteries.

Lithium-oxygen batteries are among the most attractive alternatives for future electrified transportation. However, their practical application is hindered by many obstacles. Due to the insulating nature of Li2 O2 product and the slow kinetics of reactions, attaining sustainable low charge overpotentials at high rates becomes a challenge resulting in the battery's early failure and low round trip efficiency. Herein, outstanding characteristics are discovered of a conductive metal organic framework (c-MOF) that promotes the growth of nanocrystalline Li2 O2 with amorphous regions. This provides a platform for the continuous growth of Li2 O2 units away from framework, enabling a fast discharge at high current rates. Moreover, the Li2 O2 structure works in synergy with the redox mediator (RM). The conductivity of the amorphous regions of the Li2 O2 allows the RM to act directly on the Li2 O2 surface instead of catalyst edges and then transport through the electrolyte to the Li2 O2 surface. This direct charge transfer enables a small charge potential of <3.7 V under high current densities (1-2 A g-1 ) sustained for a long cycle life (100-300 cycles) for large capacities (1000-2000 mAh g-1 ). These results open a new direction for utilizing c-MOFs towards advanced energy storage systems.

Molecular aspects of Omicron, vaccine development, and recombinant strain XE: A review.

The global pandemic of COVID-19 began in December 2019 and is still continuing. The past 2 years have seen the emergence of several variants that were more vicious than each other. The emergence of Omicron (B.1.1.529) proved to be a huge epidemiological concern as the rate of infection of this particular strain was enormous. The strain was identified in South Africa on November 24, 2021 and was classified as a "Variant of Concern" on November 26, 2021. The Omicron variant possessed mutations in the key RBD region, the S region, thereby increasing the affinity of ACE2 for better transmission of the virus. Antibody resistance was found in this variant and it was able to reduce vaccine efficiency of vaccines. The need for a booster vaccine was brought forth due to the prevalence of the Omicron variant and, subsequently, this led to targeted research and development of variant-specific vaccines and booster dosage. This review discusses broadly the genomic characters and features of Omicron along with its specific mutations, evolution, antibody resistance, and evasion, utilization of CRISPR-Cas12a assay for Omicron detection, T-cell immunity elicited by vaccines against Omicron, and strategies to decrease Omicron infection along with COVID-19 and it also discusses on XE recombinant variant and on infectivity of BA.2 subvariant of Omicron.

Luteolin: a flavonoid with a multifaceted anticancer potential.

Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.

Training community health workers for the COVID-19 response, India.

OBJECTIVE: To report experiences in Bihar, India's most densely populated state, with a state government programme to train community health workers (CHWs) to combat the coronavirus disease 2019 (COVID-19) pandemic in the state's predominantly rural population of 128 million. METHODS: In May 2021, during the second wave of the COVID-19 pandemic in India, the Bihari government initiated a 1-day COVID-19 training programme for rural, unaccredited CHWs who had recently completed a community health education course from the National Institute of Open Schooling. The use of primary health centre buildings and doctors to deliver COVID-19 training and the existence of certification data on CHWs who participated in the community health education course streamlined implementation and minimized costs. After COVID-19 training, CHWs were paid as first responders and COVID-19 treatment workers by the Bihari government. FINDINGS: Overall, 15 000 CHWs in Bihar completed the COVID-19 training programme in 2021 and a further 30 000 were enrolled. A survey of CHWs carried out after COVID-19 training had started found that 80% (81/102) were satisfied with training and felt they were receiving information from reliable sources. CONCLUSION: The training and mobilization of a team of CHWs helped ease pressure on a stressed, rural, health-care system in Bihar and improved its preparedness for future COVID-19 outbreaks. The success of the training programme illustrates how local initiatives can help address gaps in the health workforce and extend the reach of public health care into rural areas, in addition to improving COVID-19 responses.