Abstract
In this issue, we have two interesting and informative reviews dealing with coronavirus disease 2019 (COVID-19). In the first, Azargoonjahromi discusses the implications of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the brain. In this review, the author discusses cytokine storms, the damaging of brain cells, and the impact of SARS-CoV-2 on neurons, oligodendrocytes, astrocytes, and microglia. Finally, we attempt to understand the mechanisms at play during Long COVID and the associated brain fog.
As soon as we saw early cases of COVID-19, it quickly became apparent that there would be a broad range of disease severity based on many factors and determinants of health. In particular, underlying issues, such as type 2 diabetes (T2D), were immediate concerns as such health issues were suspected to worsen disease severity. Once COVID-19 vaccines became available, the impact of T2D on immune responses to the vaccines was also a major concern. In a second review in this issue, Yuan et al. updates us on the research progress on weak immune responses to COVID-19 vaccines in individuals living with type 2 diabetes.
Staying with the topic of vaccines against viruses, in a research article by Boone et al. focused on the turkey herpesvirus (HVT), the authors aimed to test whether the addition of CpG oligodeoxynucleotides (CpG ODN) to the HVT vaccine could have an adjuvant effect. The team measured the frequencies of macrophages, gamma-delta T cells, CD4 and CD8 T cell subsets, as well as double positives and T cell activation markers. The authors indeed observed improvements in some of these parameters when CpG ODN was included, allowing them to conclude that CpG ODN administration in ovo with or without HVT significantly increased the frequencies of activated CD4+ and CD8+ T cells.
In another article that focused on T cell responses, Kaushal et al. studied Kyasanur Forest Disease Virus (KFDV), which is a tick-borne flavivirus that causes hemorrhagic fever and is associated with 3–5% mortality rates. To gain insights into the pathogenesis of this virus, the authors isolated peripheral blood mononuclear cells from KFD cases and healthy controls and exposed them to γ-inactivated KFDV antigen ex vivo. The team noted that a significant increase in lymphoproliferation and a high frequency of CD4+ and CD8+ T cells secreting IFN-γ against γ-inactivated KFDV antigen were found in the recovered KFD group. The authors believe these findings would be relevant to KFD vaccine development.
The topic of waning immunity might have seemed like a new and disappointing concept for many in recent years as we saw the limitations of the COVID-19 vaccines, but in the world of immunology, waning of immunity was and is expected. We hope it doesn't happen too fast, of course, but it is inevitable. Fortunately, virus- or vaccine-induced immunity seems to wane more slowly for some viruses and vaccines than it does for others. The hepatitis B virus vaccine has often been a shining example of a vaccine that provides decades of protection, and it somewhat sets a standard by which many other vaccines are measured. In a study by Niu et al., the authors investigated the relationship between age, sex, and anti-HBs antibody levels, as well as HBsAg/HBeAg positivity. Interestingly, they found a significant difference in anti-HBs titer between sexes and across age groups. The authors concluded that anti-HBs levels indeed decline following vaccination, and they expressed concern that 15–18 years of age adolescents showed the highest prevalence of serum markers HBsAg/HBeAg.
The topic of immune senescence has always been highly relevant, but this interest was enhanced when checkpoint inhibitors were developed. Given the success of checkpoint inhibitors in cancer therapy, the notion of taking the brakes off T cells in chronic infection is now also a hot topic. In a study by Wu et al., the mRNA expression patterns of Epstein–Barr virus (EBV) lytic genes along with PD-L1 genes was monitored in an EBV-positive nasopharyngeal carcinoma (NPG) cell line. The results showed that EBV immediate-early gene BRLF1 (Rta) had potential for PD-L1 activation, and they found that Rta expression enhanced PD-L1 expression. The authors went on to show that Rta-induced PD-L1 expression could impair IL-2 secretion from T cells. Based on these findings, the authors proposed that RTa might be important in NPG and could be a potential new therapeutic target.
In closing, we are ever grateful to all authors for submitting their outstanding work to Viral Immunology, all reviewers for volunteering their time and expertise, funding sources for making the work possible, and of course, to all study subjects for providing crucial samples.