Persistent SARS-2 infections contribute to long COVID-19

Med Hypotheses. 2021 Apr;149:110538. doi: 10.1016/j.mehy.2021.110538. Epub 2021 Feb 16.


COVID-19 is a serious disease that has infected more than 40 million people. Beside significant mortality, the SARS-CoV-2 infection causes considerable and sustained morbidity, dubbed long COVID. This paper argues that some of this morbidity may be due to a persistent systemic infection. Persistent infection is indicated by continued virus RNA shedding. The virus' superantigen could overstimulate anti-virus immune responses, and thereby induce negative feedback loops, that paradoxically allow the virus to persist. The superantigen would induce strong immune response to any residual infection. This hypothesis suggests that clearing the virus infection completely would be an appropriate intervention against long COVID.

MeSH terms

  • Antibodies, Viral / immunology
  • Antiviral Agents / therapeutic use
  • Autoimmunity
  • COVID-19 / complications*
  • COVID-19 / immunology
  • COVID-19 / virology
  • Cytokine Release Syndrome
  • Humans
  • Inflammation
  • Models, Theoretical
  • SARS-CoV-2*
  • Superantigens / immunology
  • Virus Shedding*


  • Antibodies, Viral
  • Antiviral Agents
  • Superantigens

Supplementary concepts

  • post-acute COVID-19 syndrome