Why does the covid have repeated fevers, and generally at night?

Not only the new crown, but most fevers caused by pathogen infections will show cyclical changes. This is related to pathogen characteristics, as well as the body's own thermoregulatory mechanisms.

As thermostatic animals, we have a specialized thermoregulatory mechanism in our bodies: it regulates body temperature through the thermoregulation point of the hypothalamus.

The thermostat is like a ruler.

When the human body is facing the threat of high temperature, the hypothalamus promotes the cooling of the human body by promoting increased secretion of sweat glands, telangiectasia, and decreased heat production in the muscle liver;

When the human body is threatened by low temperature, the hypothalamus promotes the warming of the human body by promoting decreased secretion of sweat glands, constriction of capillaries, and increased thermogenesis of muscles and livers;

Although the temperature setting point is usually around 37°C, it is not static:

For example, pathogen infection, inflammatory response, endocrine disorders, metabolic disorders, thermoregulatory center dysfunction, autonomic dysfunction, other diseases, etc., may cause the temperature regulation point to rise, resulting in fever.

In daily life, the fever encountered by ordinary people is mainly caused by pathogen infection (humoral route) and inflammatory reaction (skin sensory nerve pathway).

Changes in the point of temperature regulation are mainly achieved by prostaglandin E2 (PGE2) [1].

Humoral route

When pathogens invade the human body and cause an immune response, they will prompt immune cells (monocytes, macrophages, endothelial cells, lymphocytes, etc.) to release a series of cytokines.

Some thermogenic factors in cytokines (eg, interleukin 1, 2, 6, interferon, tumor necrosis factor, etc.) can promote PGE2 release through direct or indirect pathways [2].

When PGE2 binds to PGE2 receptors in the hypothalamus, it activates neurons in the anterior part of the hypothalamus and raises the body temperature to set the point.

Neural pathways

When local inflammation occurs, PGE2 forms at the site of inflammation and heats up by activating cold-sensitive neurons in the skin and transmitting firing signals to the brain [3].

In addition to the cutaneous sensory nerve pathway, body temperature can be elevated through the vagus nerve (mainly the liver). The vagus pathway, independent of PGE2, acts purely through epinephrine [4].

The main reason why pathogens cause the temperature setting point to rise is that high temperatures can suppress pathogens (enhance immunity, weaken pathogens), which is an adaptive evolution.

As the pathogen is cleared, the immune response ends, and the inflammatory response ends, PGE2 levels decrease to normal levels. Coupled with the corresponding negative temperature regulation mechanism to play a role, the body temperature adjustment point will return to normal levels.

It can be seen that the level of body temperature reflects the level of PGE2, and the level of PGE2 reflects the strength of the immune response. The strength of an individual's immune response is often related to the amount of viral load.

Of course, the fever of the human body infected with different pathogens is directly related to the infectious capacity of the pathogen itself, the amount of virulence, and the strength of the human immune system.

After infection with different pathogens, body temperature manifestations are varied [5][6][7]:

Subtle differences in the description of thermodynamic performance from other data are differences in the selected data and literature

A: Retained fever, body temperature above 39~40 °C, manifested as 24-hour high body temperature, the highest and lowest temperature difference is less than 1 °C, mainly seen in lobar and gram-negative pneumonia, typhoid, acute bacterial meningitis, urinary tract infection, tuberculosis, fungal infection, etc. [8]. This type of viral infection may also be seen.

B: Short-term persistent acute fever, manifested as acute fever but generally resolves within 24 hours. Both acute infection and some common diseases can occur.

C: Tensile fever, body temperature above 39 °C, large fluctuations, temperature fluctuations of more than 2 °C within 24 hours. It is more common in bacterial infections such as sepsis, infective endocarditis, rickettsial infection, and brucellosis. Viral infections are often characterized by galloping fever and are self-limited.

D: intermittent fever, body temperature often rises sharply above 39 °C, subsides after a few hours, high fever and fever-free periods appear repeatedly alternately, and the fever-free period can reach up to 1 day to several days (mainly divided into 24 hours, 48 hours, 72 hours). It is more common in malaria, purulent infection, tuberculosis, schistosomiasis, sepsis, lymphoma, spirochete infection, kala-azar, acute pyelonephritis [9], and intermittent fever may also be present in other bacterial and viral infections.

E: Wave fever, more common in brucellosis [10], sheep are the main source of infection, followed by pigs and cattle.

F: Relapsing fever [11], a typical symptom caused by relapsing fever treponemal infection, mostly transmitted by lice and tick bites, and generally not seen in other conditions. (The heat of each cycle, in fact, is not as regular as in the figure, and can show waveforms such as residual heat, relaxation heat, and intermittent heat). However, it is also seen in malaria, lymphoma, spirochetesis, periodic neutropenia, and rat bite fever [12].

Different pathogens, after infecting different populations, have different developments, and most of them show diurnal changes [13].

But in fact, it can be seen that because some bacteria and fungi have a more typical life cycle in the human body, the fluctuations in body temperature caused by them are also more typical. Relatively speaking, the cyclicality of the virus is difficult to have typical manifestations, and individual differences are greater.

As a virus, a pathogen, the new coronavirus also causes PGE2 to rise mainly through an immune response, resulting in fever in the human body [14][15]. The severity of COVID symptoms also showed a positive correlation with PGE2 levels [16].

As many as 88.7% of hospitalized patients develop fever [17].

It presents with fever, intermittent and one of the common symptoms [18].

The development of the new crown virus in the human body has this relationship with body temperature:

When the new coronavirus replicates in the human body, as the amount of virus increases, the immune response strengthens, which will lead to a gradual increase in the temperature adjustment point.

When the body temperature rises, the new coronavirus is suppressed, and as the viral load decreases, the immune response weakens. The stubborn new coronavirus may invade cells again and replicate continuously.

After developing to a sufficient scale, it again causes a strong immune response, causing an increase in body temperature.

……

In this way, fever and viral load rise and fall, constantly cycling.

Although most people's immune system will eventually destroy the new crown virus, there are also some people (10~20%) whose immune system cannot completely eliminate them, thus showing a long new crown and being in the painful torment of long-term symptoms.

For asymptomatic, it is usually because there are enough viruses infected or the immune system is strong enough. After causing an immune response, the new coronavirus is directly eliminated, and the cytokines produced have returned to normal levels before causing an increase in body temperature.

For mild cases with a short duration of one-time fever, the virus may have been cleared by the first fever cycle.

Of course, for most mild cases, the virus is usually cleared within a few cycles.

In addition to the typical course, some recurrent fevers may involve more complex causes, such as the formation of abscesses from deep infection, repeated exposure to antigens due to various other causes, drug allergies, tissue necrosis, and even some unknown causes [19].

Isn't the fever high in Covid?

Since Omicron is already far less toxic than Delta, for most people, there is no cytokine storm like severe disease. Therefore, it is mainly mild, so the fever degree of some people is indeed not high.

But this is still closely related to the toxicity of the strain branch, the amount of virus infection, and the autoimmune system, and there are great individual differences.

Some people may have an acute hyperthermia and quickly suppress the virus and then recover; But some people may have a long-term low-grade fever, repeated and unable to completely remove the virus.

Why is the fever cycle often related to the day and night cycle?

It is mainly reflected in two points:

1. The temperature cycle of the human body changes with day and night.

Body temperatures are higher during the day and lower at night, usually within 1°C. It is regulated by the biological clock and is related to metabolism and endocrine.

When the amount of viral infection is low enough, the increase in fever itself is not obvious, and the body temperature cycle is naturally the same as the circadian rhythm.

For example, with an average temperature rise of 0.6°C, fever appears during the day and looks normal at night.

2. Viral activity is affected by temperature, and the immune response is regulated by circadian rhythm [20].

When sleeping at night, as metabolism decreases, related physiological functions weaken, and as body temperature decreases, pathogens may behave more actively.

Regarding immunity, my original answer mentioned that when you sleep, immunity is lower. In fact, there are certain problems with this statement. To be precise, the immunity is the lowest before going to bed, and after sleeping, the immunity will gradually increase, and the immunity in the second half of the night and early morning is the strongest.

The immune system works by the balance of anti-inflammatory factors and pro-inflammatory factors. In short, pro-inflammatory factors make the immune system more active, resulting in an inflammatory response and the elimination of pathogens, but they are also more likely to cause cytokine storms and cause damage to autologous cell tissue. Anti-inflammatory factors suppress the immune system and can protect autologous cell tissue, but they may also make it easier for pathogens to invade and multiply. That is to say, whether the anti-inflammatory factor or the pro-inflammatory factor is too strong, it is not good for the human body, and it needs to be in a state of dynamic balance.

Nocturnal time is a key process in the balance shift between pro-inflammatory and anti-inflammatory factors [21][22].

Before falling asleep, anti-inflammatory factors continue for a day of activity, inflammatory factors reach the lowest level, and the immune response is the weakest. After falling asleep, with the gradual increase of pro-inflammatory factors, the body's immune response will gradually increase, and the immune response will be most intense after the second half of the night.

Too strong an immune response is more likely to pose a threat to the body. Acute inflammatory symptoms and the risk of death in humans also occur mainly during this time period.

Especially during viral infection, the virus develops rapidly when the immunity weakens in the evening, and when the immune response is strongest in the second half of the night, it is more likely to have a serious immune response, resulting in a rapid increase in PGE2 levels, causing an acute increase in body temperature.

Therefore, acute fever, or periodic high fever, mostly occurs at night.

Although acutely elevated body temperature helps suppress the development of the virus, it is also often more dangerous.

Acute high fever at night, especially need to pay attention to cooling treatment.

High fever is generally 2~4 °C higher than normal body temperature, far exceeding the normal day and night body temperature difference. Compared with the first case, the periodic changes in body temperature cycle and viral load and immune rhythm at this time show a stronger correlation.

Of course, it is precisely because of the existence of such a cycle in the immune rhythm that sleeping more is conducive to recovery after influenza and new crown infection.

Since most people are impressed by a high fever, they will also be more impressed by a fever late at night.

In short, the fever caused by the new crown infection will indeed show changes in the day and night cycle as a whole, but the specific degree of fever and fluctuation characteristics will have obvious individual differences.

Since the increase in body temperature is conducive to inhibiting pathogens, increasing the upper fever reducing drugs generally has certain side effects, so it is generally recommended that antipyretics below 38.5 °C are not applicable, and above 38.5 °C can be considered, and fever reduction is required beyond 40 °C.

It is worth noting that each person's physique is different, and the tolerance of high fever is different. Whether to cool down can be self-judged according to the degree of discomfort.

reference

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