Host genetics and infectious disease: new tools, insights and translational opportunities.

Understanding how human genetics influence infectious disease susceptibility offers the opportunity for new insights into pathogenesis, potential drug targets, risk stratification, response to therapy and vaccination. As new infectious diseases continue to emerge, together with growing levels of antimicrobial resistance and an increasing awareness of substantial differences between populations in genetic associations, the need for such work is expanding. In this Review, we illustrate how our understanding of the host-pathogen relationship is advancing through holistic approaches, describing current strategies to investigate the role of host genetic variation in established and emerging infections, including COVID-19, the need for wider application to diverse global populations mirroring the burden of disease, the impact of pathogen and vector genetic diversity and a broad array of immune and inflammation phenotypes that can be mapped as traits in health and disease. Insights from study of inborn errors of immunity and multi-omics profiling together with developments in analytical methods are further advancing our knowledge of this important area.

Interpretable detection of novel human viruses from genome sequencing data.

Viruses evolve extremely quickly, so reliable methods for viral host prediction are necessary to safeguard biosecurity and biosafety alike. Novel human-infecting viruses are difficult to detect with standard bioinformatics workflows. Here, we predict whether a virus can infect humans directly from next-generation sequencing reads. We show that deep neural architectures significantly outperform both shallow machine learning and standard, homology-based algorithms, cutting the error rates in half and generalizing to taxonomic units distant from those presented during training. Further, we develop a suite of interpretability tools and show that it can be applied also to other models beyond the host prediction task. We propose a new approach for convolutional filter visualization to disentangle the information content of each nucleotide from its contribution to the final classification decision. Nucleotide-resolution maps of the learned associations between pathogen genomes and the infectious phenotype can be used to detect regions of interest in novel agents, for example, the SARS-CoV-2 coronavirus, unknown before it caused a COVID-19 pandemic in 2020. All methods presented here are implemented as easy-to-install packages not only enabling analysis of NGS datasets without requiring any deep learning skills, but also allowing advanced users to easily train and explain new models for genomics.

Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection.

Coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses increase oxidative stress in the body leading to cellular and tissue damage. To combat this, administration of high-dose vitamin C (ascorbic acid or ascorbate), in addition to standard conventional supportive treatments, has been shown to be a safe and effective therapy for severe cases of respiratory viral infection. Morbidity, mortality, infectiveness and spread of infectious diseases are dependent on the host-pathogen relationship. Given the lack of effective and safe antiviral drugs for coronaviruses, there should be more attention in supporting host immune defence, cytoprotection and immunoregulation. Implementation of high-dose vitamin C therapy could dramatically reduce the need for high doses of corticosteroids, antibacterials and antiviral drugs that may be immunosuppressive, adrenal depressive and toxic, complicating the disease course. In order to effectively fight the novel SARS-CoV-2 virus, medical professionals should explore readily available pharmaceutical and nutritional therapeutic agents with proven antioxidant, anti-inflammatory and immunosupportive properties. Supplemental vitamin C may also provide additional benefits for the prevention of viral infections, shorten the disease course and lessen complications of the disease.

Will We Miss the Opportunity Again?

Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.