Effect of a fever in viral infections — the ‘Goldilocks’ phenomenon?

Abstract

Acute infections, including those due to Coronaviridae and other viruses, often stimulate a febrile response. A mild fever appears to improve outcome; it appears to diminish viral replication by several mechanisms, including virion entry into host cells and genome transcription, and improving host defence mechanisms against the pathogen. However, a fever may also damage host cellular and tissue function and increase metabolic demands. At temperatures at the lower end of the febrile range, the benefit of the fever appears to outweigh the detrimental effects. However, at higher temperatures, the outcome worsens, suggesting that the disadvantages of fever on the host predominate. A non-infective fever is associated with a worse outcome at lower temperatures, suggesting that hyperthermia carries less benefit in the absence of infection. This review discusses the risks and benefits of a fever on the host response, focusing on the effects of a fever on viral replication and host response, and the detrimental effect on the host.

Keywords: Fever; Virus; Coronavirus; Infection; Body temperature regulation; Hyperthermia

Core Tip: Acute infections, including those due to coronavirus and other viruses, often stimulate a febrile response. A mild fever appears to improve outcome; it appears to diminish viral replication by several mechanisms, and improve host defence mechanisms against the pathogen. At higher temperatures, the outcome worsens, suggesting that the risks of fever on the host outweigh the benefit. A non-infective fever is associated with a worse outcome at lower temperatures. This paper discusses why a mild fever may be better than no, or very high fever.