Why does hypothermia sometimes follow a fever from influenza or COVID-19?
Executive summary
Hypothermia can follow or replace fever in some influenza and COVID-19 cases because severe or dysregulated systemic inflammation, central thermoregulatory dysfunction and host factors (age, energy reserves, medications) can flip the body's set‑point and heat balance from producing heat to losing it [1] [2]. Case reports and clinical summaries document hypothermia in COVID-19 and viral illnesses, but the phenomenon remains relatively uncommon and mechanistically incompletely understood [3] [2].
1. Clinical pattern and how often this occurs
Clinicians have observed hypothermia in a minority of severe infections: most patients with viral illnesses like influenza or SARS‑CoV‑2 present with fever, but case reports and small series describe patients who develop low core temperature either early, alternating with fever, or later in the illness course—findings recorded in COVID‑19 case reports and in reviews of systemic inflammation [2] [3] [4] [1]. Large observational studies suggest hypothermia is less common than fever but, when present in hospitalized infectious patients, it is associated with worse outcomes in many reports, for example in sepsis and in some COVID‑19 cohorts [5] [6] [3].
2. Inflammation can produce fever or hypothermia depending on context
Fever and hypothermia are both regulated responses to systemic inflammation driven by endogenous mediators—“pyrogens” produce fever and other mediators (sometimes called cryogens) can produce hypothermia—so the same innate immune activation can yield either outcome depending on the magnitude, timing and context of inflammatory signaling [1]. Animal models and human sepsis data show that mild or early inflammatory stimuli tend to trigger fever, whereas severe or dysregulated inflammation (and certain doses or types of stimuli) can trigger hypothermia—an adaptive or maladaptive switch that is not fully resolved scientifically [1] [2].
3. Central thermoregulation and viral neurotropism: the hypothalamus as a likely player
SARS‑CoV‑2 and other pathogens can affect central autonomic structures involved in temperature regulation; several reports suggest hypothalamic or central autonomic dysfunction may underlie temperature swings including paroxysmal hypothermia after COVID‑19, and the hypothalamus is known to express viral entry proteins that could permit direct or inflammation‑mediated injury [4]. Case descriptions document alternating fever and hypothermia and hypothesize hypothalamic involvement and central dysautonomia, but these remain hypotheses requiring more systematic neuropathologic and physiologic study [4] [2].
4. Peripheral contributors: energy balance, heat loss and iatrogenic causes
Beyond central mechanisms, peripheral factors explain why a patient might cool down after a febrile phase: severe illness depletes metabolic reserves needed for heat production (e.g., prolonged catabolism, hypoglycemia, or malnutrition), organ dysfunction can impair heat generation, and treatments or home measures—excessive antipyretic dosing, aggressive cooling attempts or environmental exposure—can hasten temperature drops; case series and patient reports have highlighted antipyretic overuse and energy depletion as contributors [7] [8] [5]. Measurement issues with peripheral thermometers can also misclassify temperature, so clinical context and core measurements matter [9].
5. Prognosis, treatment implications and controversies
Hypothermia in the setting of infection often signals more severe or dysregulated disease and has been associated with higher mortality in sepsis and some COVID‑19 reports, prompting urgent evaluation for sepsis, organ failure and reversible causes [5] [3] [6]. At the same time, randomized trials in sepsis have cautioned against blanket aggressive temperature suppression because fever can support immune functions, so clinicians must balance heating or cooling strategies against the underlying pathophysiology rather than reflexively treating numbers [10] [1].
6. What remains uncertain and where research should focus
Existing evidence is largely case reports, observational cohorts and mechanistic reviews: the precise mediators that switch an inflammatory response from fever to hypothermia are incompletely identified, the relative roles of direct viral neuroinvasion versus systemic cytokine patterns are unsettled, and whether hypothermia in viral illness is sometimes adaptive or always maladaptive is debated—prospective physiologic and neuropathologic studies are needed to move beyond hypothesis [1] [2] [4]. Current reporting documents the phenomenon and plausible mechanisms but cannot definitively rank causes or prescribe universal management beyond standard sepsis and hypothermia care [3] [8].