PMC:7148425 / 2531-4900 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7148425","sourcedb":"PMC","sourceid":"7148425","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7148425","text":"COVID immunopathology and potential interventions\nThere is no pre-existing immunity to a virus not previously encountered except via cross-reactivity or shared viral antigen, as is sometimes the case for seasonal influenza strains. As SARS-CoV-2 is almost certainly completely novel for at least the vast majority of people, the virus enjoys unrestrained entry into host cells which then rely on intracellular (cell-intrinsic) anti-viral defence mechanisms [4]. If these fail, cell death releases damage-associated molecules (DAMPs) and viral particles triggering inflammatory reactions. Severe acute respiratory syndrome is caused by dysregulated over-exuberant inflammatory responses that can progress to a systemic sepsis-like “cytokine storm” [5], which together with effects of the virus also directly infecting other organs, not just the lung, can result in multiple organ failure. The aim of prophylactic vaccination of course is to induce sufficient neutralising antibody to prevent infection and sufficient numbers of virus-specific resident memory cytotoxic T cells in the lung to prevent viral replication. This requires the presence and efficient cooperation of antigen-presenting cells, T cells and B cells within a correctly functioning microenvironment (lymph node). When vaccination is unable to elicit qualitatively or quantitatively sufficient protective antibody, host cell infection will still take place, and may trigger sequelae described above. Given the rapidity and degree with which SARS-CoV-2 can cause immunopathology in the lung, vaccines would have to be highly efficient in generating neutralising antibody as well as protective cell mediated local immunity to prevent this sequence of events. Achieving such immune protection by a vaccine is quite feasible in the young, but it may prove to be challenging in old populations as evidenced by the low efficacy of seasonal influenza vaccine in such populations. Alternatively, adoptive immunotherapy with neutralising monoclonal antibody, as in cancer treatment, may be a possibility, and several companies are working on this. However, repeated i.v. infusion of sufficient antibody does not seem a priori an optimal approach. Clearly, traditional vaccination to stimulate the patient’s own response would be preferable, but how likely is it that that could be accomplished in older 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