Fever: current view on its significance in the COVID-19 era and the people’s attitude to this symptom

Our purpose was to evaluate the scientific data on occurrence of fever in the infectious conditions as well as studying peculiar features of fever in children at pediatric unit with assessment of attitude towards pyrexia among general population. Fever is a general response to infection which occurs across warm- and cold-blooded vertebrates for over 600 million years of evolution. The response to fever is mediated by integrated physiological and neural circuitries and provides a survival advantage during infection. The world experience in fever studies shows an ambiguous effectiveness of combating it, both under septic conditions and non-septic events. In a systematic review of 42 studies conducted by Rumbus Z. and other authors, the mortality rate in patients with sepsis with fever greater than 38 °C was 22.2%, with normothermia – 31.2%, and was highest in patients with hypothermia less than 36.0 °C – 47.3%. That is, fever was associated with reduced, and hypothermia with increased mortality in septic patients. All attempts to achieve improved survival by usage of antipyretics and physical cooling in sepsis have failed. Given the rising mortality rates during the COVID-19 pandemic, we may neglect a key aspect of the immunological response. Higher body temperature inhibits growth of microorganisms, enhances the effects of antibiotics on bacteria in biofilms, improves the survival of neutrophils, stimulates interferon productions. The heat shock proteins have a cytoprotective effect; the pyrogenic cytokines stimulate lymphocyte differentiation and exert other significant effects. However, the mechanisms of switching from pro-inflammatory to anti-inflammatory response as well as the origins of cytokine and septic shock remain understudied. It is important to look at pyrexia from the viewpoint of the body integrity. The continuum theory (unified theory of diseases) suggests that the constant fight against fever and acute inflammation causes a transition from a response to the pathogen to another, first subacute and, later to chronic level of inflammation, which excludes the possibility of acute inflammation being a predictor of ageing.

The presented review of some chronic inflammatory diseases showed this age dependence. In clinical histories, a decreased frequency and severity of fever may be observed during the onset of such chronic diseases as diabetes mellitus, bronchial asthma, chronic headaches, hypertension and post-viral syndrome. This trend suggests a revision of approaches to treatment of acute inflammation in general population. Pediatric patients exhibit the most pronounced fever and have less common chronic diseases overall. However, in recent decades a trend is noted for increase in chronic diseases among children. What is the cause of pediatric fever, and how common is usage of antipyretic drugs and other methods of fever therapy in general population? For this purpose, 300 parents living in the rural areas, and 300 urban parents of children aged 4 to 5 years have been surveyed during the non-epidemic period upon their visit to pediatric polyclinics.

Fever was most often a sign of acute respiratory infection (82.0% of cases); other acute inflammatory conditions were less common. Duration of pediatric fever exceeded 3 days in 77.0% of patients, its grade was < 39% (58.0% of the cases). High febrility was observed in 40.3% of patients and hyperthermia above 41 °С – in 1.7% of children. In the studied cohort, 21.0% had documented diseases; chronic inflammatory diseases were observed only in 9.0% of cases. With pyrexia, 96.3% of parents are anxious, have a fear of fever and use antipyretic drugs and other treatment. Febrile seizures were observed in 3.3% of pediatric patients, other adverse events were observed in 10.3% of respondents. The reported pyrophobia among the population is not justified, since fever in the child population is, generally, a sign of acute infectious disease with high temperature being is a protective reaction. The fight against pyrexia can adversely affect not only the further course of the disease, but also affect the health condition in the future, actively interfering with serious pathogenetic mechanisms.