Most microorganisms are based on a DNA genome. Some viruses, including the coronavirus, have RNA-based genomes instead. In general, viral RNA genomes are much more mutation-prone than those based on DNA. This distinction is important because RNA-based viral mutations have a greater potential for increased virulence, greater transmissibility. Such are the concerns with the variants developing in the SARS-CoV-2 virus. Different variants are evolving from “mutations” of the viral genome. Studies have shown that some variants spread more quickly than others demonstrating mutation in the virus’s spike protein (more on this below), representing a potential risk of worsening the pandemic.
Viruses are not living cells or organisms. They require a living host to exploit or infect (enter) so they can replicate to complete their life cycle (Figure 7.1). The invading virus uses its genomic DNA or RNA to replicate in the host cell. Coronaviruses (CoV) are a family of RNA viruses that typically cause mild respiratory disease in humans. They include SARS-CoV-1, thought to be driven by the spillover of bat-adapted CoVs into an intermediate host (see below). The novel coronavirus (SARS- CoV-2) is a single positive-strand RNA virus that is the largest genome known. Thus, these viruses are poorly adapted to the human host and if transmitted to humans, they are generally associated with more severe clinical presentations.
Coronavirus disease leads to fast activation of innate immune cells, especially in patients developing severe disease. Innate immune activation, levels of many proinflammatory effector cytokines (e.g., TNF, IL-1b, IL-6, IL-8, G-CSF [granulocyte colony-stimulating factor] and GM-CSF [granulocyte-macrophage
colony-stimulating factor]), as well as higher levels of chemokines (e.g., MCP1, IP10, and MIP1a) leaving virtually all organ systems vulnerable to adverse effects from the novel coronavirus. The pathogenesis and life cycle of SARS-CoV-2 includes a complex of RNA genomic transfers and regenerations to produce the proliferation of the virus. The extracellular and intracellular (host cytoplasm) processes involved are illustrated in Fig. 7.1.
The severity and the clinical picture of the immune response in many patients could even be related to the activation of an exaggerated immune mechanism. The levels of some T cell-derived cytokines (e.g., IL-17) are increased often producing a “cytokine storm” or hyperinflammatory state. This chronic inflammatory (CI) clinical response leaves virtually all organ systems vulnerable to adverse effects from the virus. The hypothesis that SARS-CoV-1 (or other, antigenically similar CoV-1) has silently infected a significant proportion of the population, inducing “herd immunity” (see Blog #42) needs to be confirmed. Indeed, immunity against the infection or patterns of semi-immunity (capacity of the immune system to avoid severe infection) may be due to cellular immunity rather than humoral immune responses. Animal models suggest that the efficiency of T lymphocyte-mediated immune responses is also pivotal for controlling SARS-CoV infections. Both IgG and IgM titers plateaued within 6 days after seroconversion [17]. Thus, serological testing may be helpful for the diagnosis of suspected patients with negative reverse transcriptase-polymerase-chain-reaction (RT-PCR) (an antigen diagnostic test – Blog #36) and for the identification of asymptomatic infections.
There is currently no data on the specific role of either humoral or cellular immunity or innate immunity in patients recovering from COVID-19. T lymphocytes responsible for clinically relevant antiviral immune responses have a significant chance to be locally present in, or close to, respiratory epithelia. It is very possible that the exclusive detection of humoral immunity against SARS-CoV-2 leads to an underestimation of the anti-SARS-CoV-2 immune responses. It becomes plausible that, after infection by SARS-CoV-2, a sort of race decides the course of the events. Either a cellular innate immune response rapidly clears SARS-CoV-2 without any (or mild) clinical signs of infection or the virus causes a state of immunosuppression that debilitates and sometimes overwhelms the host’s (human) defense
Discussion Questions:
RNA viruses differ from DNA viruses upon entering a cell cytoplasm. Can you describe the difference(s)?
The severity and the clinical picture of the inflammatory response in many patients could be related to the activation of an exaggerated immune mechanism. What is this response called and what is a possible cause?
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