Long interspersed nuclear element-1 (LINE-1) retrotransposition is a major hallmark of cancer accompanied by global chromosomal instability, genomic instability, and genetic heterogeneity and has become one indicator for the occurrence, development, and poor prognosis of many diseases. LINE-1 also modulates the immune system and affects the immune microenvironment in a variety of ways. Aberrant expression of LINE-1 retrotransposon can provide strong stimuli for an innate immune response, activate the immune system, and induce autoimmunity and inflammation. Among HERVs, one of the most studied is the W group, which is the sole HERV group specifically mobilized by the long interspersed element-1 (LINE-1) machinery, providing a source of novel insertions by retrotransposition of HERV-W processed pseudogenes, and comprising a member encoding a functional envelope protein coopted for human placentation. The HERV-W group has been intensively investigated for its putative role in several diseases, such as cancer, inflammation, and autoimmunity. There is supporting evidence of this interaction: data indicating the efficiency of antiretroviral drugs at the early stage of COVID-19, the isolation of SARS-CoV-2 for a long time after recovery, the persistence of coronavirus infections, and changes in the L1 retrotransposon expression patterns in the lung tissues of COVID-19 patients.