Recently, scientists working out of Sweden probed the SARS-CoV-2 spike’s ability to damage DNA in SARS-CoV-2 infected hosts. A troubling prospect, the study authors focused on the lack of adaptive immunity associated with severe COVID-19 patients. Clinical microbiologist Hui Jiang working out of both Umeå University and The Wenner–Gren Institute, Stockholm University, as well as Ya-Fang Mei, the virologist lead at Umeå University, found in a laboratory study using in vitro cell lines that the SARS-CoV-2 spike protein “significantly inhibits DNA damage repair,” necessary for the adaptive immunity for recovering from severe cases of the illness. This occurs as the spike protein associated with the novel coronavirus “localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site.” The pair hypothesize: could they have discovered how COVID-19 impedes the infected patient’s adaptive immunity? More disturbingly, does this breakthrough point out that the possible side effects of full-length spike-based vaccines?
Both Hui Jiang and a Ya-Fang Mei sought to better understand the mechanism making SARS-CoV-2, the virus behind COVD-19, so adversely impactful on the human adaptive immune system in severe cases. TrialSite provides a brief breakdown for the audience based on subscriber requests.
What can happen to severe cases of COVID-19?
In severe cases, SARS-CoV-2 adversely impacts human adaptive immunity. Meaning the virus hijacks and dysregulates the patient’s “cellular machinery to replicate, assemble and spread progeny viruses.” Studies reveal that patients infected with COVID-19 had impacted lymphocyte number and function. Additionally, in severe cases, COVID-19 patients produce fewer T cells, helper T cells, and suppressor T cells. Moreover, scientists have found that in severe infection, the disease delays IgG and IgM levels, which, combined with the previous elements, indicates the degradation of the human adaptive immune system.
What was the study question that both authors pursued?
What was the mechanism by which COVID-19 suppresses adaptive immunity?
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What are two critical host surveillance systems?
Immune and DNA repair systems are primary systems that higher organisms such as humans depend on to defend against a diverse array of threats and tissue homeostasis.
The authors share that mounting evidence suggests that the two systems depend on each other’s, particularly during lymphocyte development maturation.
Key investigational question
Do SARS-CoV-2 proteins hijack the DNA damage repair system and consequently endanger adaptive immunity in vitro?
What do the two scientists from Umeå University discover?
First, the authors’ study generates evidence to support the hypothesis that adaptive immunity is adversely impacted because the spike protein hijacks the host DNA damage repair machinery. The authors’ findings suggest that the SARS-CoV-2 spike protein significantly impedes V(D)J recombination.
So how is this relevant to a common understanding of risks with COVID-19?
If these findings are accurate, we already know from clinical observations that the risk of severe illness or death increases with age and that the elderly face the highest risk from the pathogen. Perhaps this is due to the SARS-CoV-2 spike protein weakening the DNA repair system of the elderly. This would hamper V(D)J recombination and adaptive immunity.
How might COVID-19 vaccines compound the problem?
The Sweden-based research team suggests that the “full-length spike-based vaccines may inhibit the recombination of V(D)J in B cells. First, Hui Jang and Ya-Fang Mei write that another study backs the premise that “a full-length spike-based vaccine-induced lower antibody titers compared to the RBD-based vaccine.”
They propose a different approach with the COVID-19 vaccine, suggesting “that the use of antigenic epitopes of the spike as a SARS-CoV-2 vaccine might be safer and more efficacious than the full-length spike.”
What is the potential bombshell finding in this recently published study?
The authors propose ways in which SARS-CoV-2 suppresses the “host adaptive machinery.” Combined with this is the problematic implication that these side effects carry over to full-length spike-based vaccines.
What needs to happen?
Researchers must better understand how SARS-CoV-2 develops and unfolds in the human body and gain an improved understanding of the impact of the current crop of vaccines.
Lead Research/Investigator
Hui Jiang, Ph.D., Umeå University; The Wenner–Gren Institute, Stockholm University
Ya-Fang Mei, Umeå University , Virology Department Head