Hannah K. Hopkins

Chikungunya virus (CHIKV) is currently an urgent public health problem as high morbidity from the virus leaves populations with negative physical, social, and economic impacts. CHIKV has the potential to affect every organ of an individual, leaving patients with lifelong impairments which negatively affect their quality of life. In this review, we show the importance of CHIKV in research and public health by demonstrating the immunopathology of CHIKV as it presents in different organ systems. Papers used in this review were found on PubMed, using “chikungunya and [relevant organ system]”. There is a significant inflammatory response during CHIKV infection which affects several organ systems, such as the brain, heart, lungs, kidneys, skin, and joints, and the immune response to CHIKV in each organ system is unique. Whilst there is clinical evidence to suggest that serious complications can occur, there is ultimately a lack of understanding of how CHIKV can affect different organ systems. It is important for clinicians to understand the risks to their patients.

Chikungunya virus (CHIKV) is an alphavirus of the family Togaviridae with outbreaks occurring across Africa, Asia, parts of Europe, and South and Central America. There are three main lineages of CHIKV, including the West African lineage, the East Central South African (ECSA) lineage, and the Asian lineage. While CHIKV infection usually results in a self-limited febrile illness, there have been reports of concerning neurological manifestations, including encephalitis. Herein we discuss findings of over 700 cases of CHIKV encephalitis and risk factors for death. Additionally, we examined the genotypes of CHIKV associated with encephalitis and found that both the Asian and ECSA lineages were responsible for encephalitis but not the West African lineage. Protein analysis of consensus sequences of CHIKV strains associated with encephalitis identified mutations in the nsP1, nsP2, and nsP3 proteins. Reports and manuscripts of CHIKV encephalitis were inconsistent in reporting viral, demographic, and clinical features which complicated the delineation of risk factors associated with the disease and viral evolution. As climate change contributes to the range expansion of natural vectors, it is important for researchers and clinicians to consistently report patient and viral data to facilitate research and countermeasures for the ecology and epidemiology of CHIKV due to the lack of a targeted treatment or vaccine.

(1) Background: The human brain is of interest in viral research because it is often the target of viruses. Neurological infections can result in consequences in the CNS, which can result in death or lifelong sequelae. Organoids modeling the CNS are notable because they are derived from stem cells that differentiate into specific brain cells such as neural progenitors, neurons, astrocytes, and glial cells. Numerous protocols have been developed for the generation of CNS organoids, and our goal was to describe the various CNS organoid models available for viral pathogenesis research to serve as a guide to determine which protocol might be appropriate based on research goal, timeframe, and budget. (2) Methods: Articles for this review were found in Pubmed, Scopus and EMBASE. The search terms used were “brain + organoid” and “CNS + organoid” (3) Results: There are two main methods for organoid generation, and the length of time for organoid generation varied from 28 days to over 2 months. The costs for generating a population of organoids ranged from USD 1000 to 5000. (4) Conclusions: There are numerous methods for generating organoids representing multiple regions of the brain, with several types of modifications for fine-tuning the model to a researcher’s specifications. Organoid models of the CNS can serve as a platform for characterization and mechanistic studies that can reduce or eliminate the use of animals, especially for viruses that only cause disease in the human CNS.

Chikungunya virus (CHIKV) is vectored by Aedes aegypti and Aedes albopictus mosquitoes and is found throughout tropical and sub-tropical regions. While most infections cause mild symptoms such as fever and arthralgia, there have been cases in which cardiac involvement has been reported. In adults, case reports include symptoms ranging from tachycardia and arrythmia, to myocarditis and cardiac arrest. In children, case reports describe symptoms such as arrythmia, myocarditis, and heart failure. Case reports of perinatal and neonatal CHIKV infections have also described cardiovascular compromise, including myocardial hypertrophy, ventricular dysfunction, myocarditis, and death. Myocarditis refers to inflammation of the heart tissue, which can be caused by viral infection, thus becoming viral myocarditis. Since viral myocarditis is linked as a causative factor of other cardiomyopathies, including dilated cardiomyopathy, in which the heart muscle weakens and fails to pump blood properly, the connection between CHIKV and the heart is concerning. We searched Pubmed, Embase, LILACS, and Google Scholar to identify case reports of CHIKV infections where cardiac symptoms were reported. We utilized NCBI Virus and NCBI Nucleotide to explore the lineage/evolution of strains associated with these outbreaks. Statistical analysis was performed to identify which clinical features were associated with death. Phylogenetic analysis determined that CHIKV infections with cardiac symptoms are associated with the Asian, the East Central South African, and the Indian Ocean lineages. Of patients admitted to hospital, death rates ranged from 26–48%. Myocarditis, hypertension, pre-existing conditions, and the development of heart failure were significantly correlated with death. As such, clinicians should be aware in their treatment and follow-up of patients.