Exploring the rationale for thermotherapy in COVID-19

Abstract

Increased transmissibility of the pandemic severe acute respiratory coronavirus 2 (SARS-CoV-2) has been noted to occur at lower ambient temperatures. This is seemingly related to a better replication of most respiratory viruses, including SARS-CoV-2, at lower-than-core body temperatures (i.e., 33 °C vs 37 °C). Also, intrinsic characteristics of SARS-CoV-2 make it a heat-susceptible pathogen. Thermotherapy has successfully been used to combat viral infections in plants which could otherwise result in great economic losses; 90% of viruses causing infections in plants are positive-sense single-stranded ribonucleic acid (+ssRNA) viruses, a characteristic shared by SARS-CoV-2. Thus, it is possible to envision the use of heat-based interventions (thermotherapy or mild-temperature hyperthermia) in patients with COVID-19 for which moderate cycles (every 8–12 h) of mild-temperature hyperthermia (1–2 h) have been proposed. However, there are potential safety and mechanistic concerns which could limit the use of thermotherapy only to patients with mild-to-moderate COVID-19 to prevent disease progression rather than to treat patients who have already progressed to severe-to-critical COVID-19. Here, we review the characteristics of SARS-CoV-2 which make it a heat-susceptible virus, potential host mechanisms which could be enhanced at higher temperatures to aid viral clearance, and how thermotherapy could be investigated as a modality of treatment in patients with COVID-19 while taking into consideration potential risks.

Keywords:

• Thermotherapy
• non-oncologic applications of hyperthermia
• COVID-19
• SARS-CoV-2
• RNA interference

Acknowledgments

J.M.G. would like to thank ‘Dirección General de Calidad y Educación en Salud’ for supporting his participation in ‘Programa Nacional de Servicio Social en Investigación en Salud’. This work benefitted from data assembled by the ImmGen consortium. Figures were created with BioRender.com.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Instituto Nacional de Perinatología ‘Isidro Espinosa de los Reyes’ under Grant INPer 2020-1-19 awarded to N.G.S.