Журнал инфекционных заболеваний и терапии

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Two-Year History of COVID-19: A Review

Toshiharu Furukawa

In the two years since the outbreak of COVID-19, scientific advancement in relation to SARS-CoV-2 and COVID-19 has been rapid and extensive, covering virus identification, development of testing methods, epidemiological characterization, understanding of pathogenesis and immune responses, development of therapeutic agents, analysis of emerging variant strains, and development and deployment of several types of vaccines. Through trial and error in research and development for COVID-19, a certain degree of knowledge has been obtained: RT-PCR tests appear negative for some infected individuals with low levels of viral nucleic acid and appear positive for some un infectious convalescent individuals with fragmented nucleic acid; the main mechanisms of severe disease are hyper-inflammation and hyper-coagulopathy; Antiviral therapeutics may be expected to be efficacious in early phases of the disease when viral loads are still low, whereas anti-inflammatory therapeutics may be expected to be efficacious in late phases of the disease; Pre-existing cross-reactive immunity exists in some proportion of population people and modifies the immune response to emerging pathogens; Infection-induced immunity against reinfection wanes over time and upon the emergence of variants; MRNA-based vaccines may be highly effective for a short period of time, but vaccine-induced immunity wanes in half of a year; In vaccination schedules with two doses, a longer interval between the first and the second doses may lead to a higher vaccine efficacy; MRNA-vaccines may cause myocarditis, whereas virus-vectored vaccines may cause thrombosis by the production of abnormal antibody that activate platelets; Heterologous vaccination strategies may be feasible to broaden the selection of vaccines to be used for booster vaccination; Multiple-antigen exposure by infection or vaccination induces stronger and broader immunity that is effective for variants. This learning will facilitate research and development in the next pandemic.