Do current COVID-19 vaccines protect against brain damage?

Posted on 2023-02-10

Just as it did three years ago when the pandemic broke out in Wuhan, 2023 has begun with new COVID-19 variants and consequently, more cases. While the new “Kraken” variant is rapidly spreading worldwide, the transmission and mortality rates are not concerning. In fact, the UK has stopped publishing COVID-19 modelling data. According to the UKHSA Epidemiology Modelling Review Group (EMRG), the publication of specific data is no longer necessary as “vaccines and therapeutics have now allowed us to move to a phase where we are living with COVID-19". Since the 6th of January, COVID-19 activity is being monitored as any other common disease. This stability has enabled researchers to focus on understanding the virus, thus unveiling valuable information about transmission, infection, and its symptoms [1].

COVID-19 is primarily a respiratory disease caused by infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, many patients also manifest neuropsychiatric alterations, such as the loss of smell (anosmia) and taste (ageusia), headaches or dizziness. While these are not the most serious neurological consequences of COVID-19, they affect most individuals and in 10-20% of cases it can last over 12 weeks, altering the quality of life of those affected. In more severe cases, SARS-CoV-2 infection can result in cognitive impairment, epilepsy, ataxia, or encephalopathy among others [2].

Irrespective of their severity, neurological symptoms have been linked to either encephalitis, brought on by the direct viral infection of the central nervous system (CNS), or the secondary effects of the systemic SARS-CoV-2 infection, such as hypoxemia brought on by severe pneumonia. However, the neurotropism displayed by other coronaviruses, and the discovery of SARS-CoV-2 in cerebrospinal fluid from COVID-19 patients suggest direct infection of the CNS. Additionally, SARS-CoV-2 infection has also been found in the brain of multiple experimental animal models, including hamsters, ferrets, and non-human primates, as well as in transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2). While the effect of SARS-CoV-2 in the nervous system has not been characterised in detail and different pathogenic mechanisms have been proposed, important neurological alterations have been identified in patients with severe COVID-19 leading in some cases to chronic brain impairment [2,3]. While the effect of SARS-CoV-2 in the nervous system has not been characterised in detail and different pathogenic mechanisms have been proposed, important neurological alterations have been identified in patients with severe COVID-19 leading in some cases to chronic brain impairment [2,3].

Investigations from the University of Seville and the Spanish National Research Council (CSIC) have recently re-examined how SARS-CoV-2 infection developed in various brain areas of susceptible transgenic K18-hACE2 mice. Results suggest that viral replication mostly occurs in neurons 2-4 days after SARS-CoV-2 inoculation. The ventral regions of the brain, such as the hypothalamus, amygdala, and basal forebrain, showed the highest levels of infection. In later phases, viral replication spread to most brain areas, excluding the cerebellum, striatum and CA2/CA3 region of the hippocampus which only showed sporadic infection. Moreover, results revealed important neuropathological changes in K18-hACE2 mice, including neuronal loss, glia activation, and vascular damage [3].

As of today, many vaccines to tackle COVID-19 have been developed and administrated, resulting in decreased transmission rates and disease severity. Yet, it is unclear whether these prevent SARS-CoV-2 spread to the CNS and protect against brain lesions. The University of Seville and CSIC have also highlighted the potential of a poxvirus modified vaccinia virus Ankara (MVA) vector producing a human codon-optimised, full-length SARS-CoV2-S protein (MVA-CoV2-S) as a prospective COVID-19 vaccine candidate. The MVA-CoV2-S vaccine has been shown to produce a strong and long-lasting humoral and cellular SARS-Cov-2 specific immune response in several animal models. The question is, would MVA-CoV2-S be able to protect against SARS-CoV-2 brain infection and damage? [3,4,5].

Researchers then examined whether MVA-CoV2-S, expressing the SARS-CoV-2 S protein 30, protects against brain infection and associated neuropathology after SARS-CoV-2 spreading in mice [5]. K18-hACE-2 mice, which express high sensitivity to SARS-CoV-2 replication due to the enhanced hACE2 cerebral expression, were immunized with either one or two doses of MVA-S at days 0 and 28. Following immunisation, mice were infected with SARS-CoV-2 and euthanised for analysis by immunochemistry against the SARS-CoV-2 N protein. Results showed that even a single dose of the MVA-CoV2-S vaccine completely prevents SARS-CoV-2 infection in all studied brain regions. Therefore, preventing the associated brain damage, even after reinfection with the virus [3].

These findings support earlier research on the immunogenicity and effectiveness of the MVA-CoV2-S vaccine in multiple animal models [5]. In line with previous results, the MVA-CoV2-S vaccine candidate can induce an immunological response of antibodies binding to the S protein of the virus and neutralise antibodies against different variants in mouse, hamster, and macaque animal models. Moreover, the MVA-CoV2-S vaccine has been shown to induce the activation of T lymphocytes, which are essential markers for infection control [3,5]. The MVA-CoV2-S vaccine not only completely impaired brain viral replication with a single dose, but also provided long-term protection against re-infection. Interestingly, MVA-CoV2-S was able to boost the effectiveness of the vaccine candidate by inducing memory SARS-CoV-2-specific humoral and CD4+/CD6+ T cell immune response in the long-term (six months after the final dose) [3].

These findings have important long-term implications for understanding SARS-CoV-2 brain infection and the associated neurological damage. The results obtained strongly imply that the selected vaccine could prevent persistent COVID-19, independently of the number of doses administrated. While this mouse study is only the first step in demonstrating the efficacy of MVA-CoV2-S vaccine against the damage produced by SARS-CoV-2 infection, it yields promising results. "The data provided in this study with complete inhibition of SARS-CoV-2 replication in the brain mediated by the MVA-CoV2-S vaccine, together with previous studies published by the group and collaborators on the immunogenicity and efficacy of the vaccine against different variants of SARS-CoV-2, support the conduct of Phase I clinical trials with this vaccine or similar prototypes to evaluate its safety and immunogenicity," the study authors emphasize [3].

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References/Further reading:

[1] P. A. Media, “UK to stop publishing Covid modelling data,” the Guardian, Dec. 25, 2022. https://www.theguardian.com/world/2022/dec/25/uk-to-stop-publishing-covid-modelling-data (accessed Jan. 12, 2023).

[2] L. Lu et al., “The potential neurological effect of the COVID-19 vaccines: A review,” Acta Neurologica Scandinavica, vol. 144, no. 1, pp. 3–12, Jul. 2021, doi: 10.1111/ane.13417.

[3] J. Villadiego et al., “Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate,” Nature Neuroscience, Jan. 2023, doi: 10.1038/s41593-022-01242-y.

[4] Z. Huang, Y. Su, T. Zhang, and N. Xia, “A review of the safety and efficacy of current COVID-19 vaccines,” Frontiers of Medicine, vol. 16, no. 1, pp. 39–55, Feb. 2022, doi: 10.1007/s11684-021-0893-y.

[5] A. Lázaro-Frías et al., “Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice,” npj Vaccines, vol. 7, no. 1, Feb. 2022, doi: 10.1038/s41541-022-00440-w.