Is it all over if you test positive for COVID-19?

When it comes to COVID-19 infection, everyone may immediately think of the fever, headache, muscle and joint pain, sore throat, difficulty breathing, and pneumonia that they have just experienced.

Some people may not fully recover after COVID-19 infection, and may have various sequelae of COVID-19 infection, entering the "long COVID" period. Generally speaking, those who still have symptoms 4 weeks after COVID-19 infection are "long COVID-19". Studies have found that 6 months after COVID-19 infection, up to 60% of patients still have sequelae such as fatigue, difficulty breathing, cough, memory loss and difficulty concentrating, unexplained discomfort, loss of taste or smell, "brain fog", headache, gastrointestinal discomfort, as well as depression and anxiety (not all symptoms exist in the same patient).

It seems that COVID-19 infection is not as simple as "passing the test"! In addition to the various sequelae of procrastination, everyone will have various lingering concerns: Will the virus still exist after COVID-19? When will it come back? Will COVID-19 infection mainly cause gastrointestinal infection? And so on.

If we have a certain understanding of the new coronavirus, we may not be so worried. Knowing ourselves and the enemy will give us the confidence and courage to face the uncertainties of the future.

1. Novel coronavirus and its infection mechanism

As we all know, the novel coronavirus has a simple structure, consisting of an RNA chain and a shell whose main component is protein. This "low-end" structure, on the one hand, makes the virus unable to "survive on its own" and needs to rely on the infected human body to "pass on" (so it is difficult for the virus to survive on the surface of objects); on the other hand, it makes the virus difficult to kill and remove, and easy to spread. Once infected, the virus "combines" with the infected human cells. If you want to kill the virus in the body, you either "can't reach" it or you will inevitably "accidentally injure" the human cells.

Once the new coronavirus enters the human body, it will use the human body as a "copy machine" to "copy" countless new viruses. The number of viruses that enter the human body is not large at the beginning, but they will "work overtime" to replicate. During this period, the human body has no symptoms (incubation period). When the virus replicates to a certain number, it will trigger a violent "reaction" in the body, produce various symptoms, and further spread to infect others.

However, after the new coronavirus comes into contact with the human body, it needs a key "key" to get into human cells (so that the photocopier can be used), that is, the spike protein S. With this protein, the "lock" on the human cell can be opened, that is, angiotensin-converting enzyme 2 (ACE2). The new coronavirus has this "key" to enter the human body, and the danger can be imagined!

2. The role of ACE2 in COVID-19 infection

We know that about 60% of the human body is water, which is distributed in various tissues, organs and cells of the human body. The distribution process and state are strictly regulated. Once out of control, people may get sick. Among the many "managers" who manage water balance, there is an important system called the "renin-angiotensin system", which is widely present in the heart, blood vessels, muscles, brain, pancreas, gonads and adipose tissue. Simply put, this system can synthesize angiotensinogen in these organs or tissues. When the kidneys "feel" that the blood flow is reduced, they "send" renin, which can convert angiotensinogen into angiotensin I. However, angiotensin I is not yet active and needs to generate angiotensin II (or further generate III or IV) under the action of angiotensin converting enzyme (ACE) to play a role, that is, to constrict blood vessels and increase blood pressure. So, simply put, ACE has the effect of raising blood pressure, and inhibiting it can lower blood pressure. Among the various drugs for treating hypertension, there is a class of angiotensin converting enzyme inhibitors (ACEI).

However, the "lock" opened by the new coronavirus when it enters the human body is ACE2. ACE2 is similar to ACE, but has different functions. The existence of ACE2 was not discovered until 2000. It can hydrolyze angiotensin I or II into angiotensin 1-9 or angiotensin 1-7, which have the opposite effect of angiotensin II. That is, ACE raises blood pressure, while ACE2 lowers blood pressure. Of course, there are more systems that regulate blood pressure than the "renin angiotensin system", which I will not elaborate on here.

3. The mechanism of COVID-19 infection causing multiple systemic symptoms

First of all, the role of ACE2 is not only to participate in the regulation of water balance, it also has many "part-time jobs". ACE2 is also involved in regulating physiological and pathological activities such as inflammation and cell proliferation. The role of ACE2 also requires the participation of other factors, such as transmembrane serine proteases 2 and 4, which are two molecules involved in the new coronavirus infection.

In addition to the lungs, ACE2 is also expressed in many other extrapulmonary tissue cells, including the intestines, heart, liver, kidneys, nerves, and immune cells. Therefore, it is understandable why COVID-19 can cause multiple symptoms throughout the body and has been officially renamed COVID-19 infection.

For example, in the intestine, ACE2 is not only a receptor for the new coronavirus, but also regulates the intestinal uptake of tryptophan, which can improve the intestinal barrier function and reduce inflammatory cytokines, thereby protecting the beneficial bacteria in the intestine and maintaining the balance of intestinal flora. When the new coronavirus invades the intestine, ACE2 synthesis decreases, and the above protective pathways are destroyed, leading to gastrointestinal diseases. The gastrointestinal symptoms of patients infected with the new coronavirus may also involve other mechanisms. For example, the new coronavirus may affect the central nervous system and may stimulate the vagus nerve, which is closely related to gastrointestinal function, thereby causing various gastrointestinal symptoms such as nausea, vomiting and diarrhea.

Secondly, in addition to ACE2, the new coronavirus may also infect human cells through a variety of other receptor mechanisms. Recently, it has been found that more than a dozen membrane proteins can bind to the S protein of the new coronavirus alone or as a cofactor of ACE2. For example, chondroitin sulfate, which is present on the surface of most cells, neuropilin 1, which is rich in brain and nasal nerve fibers, and CD147, which is highly expressed by the immune system, are also found. There are also studies suggesting that the new coronavirus can infect cells through the endosomal pathway.

Third, ACE2 or other receptors mainly mediate the stage of the virus "invading" human cells. In fact, there are other subsequent processes. When the virus successfully invades, the body's inherent immunity is activated. In order to "protect itself", the new coronavirus needs to activate the corresponding signal mechanism to suppress the body's immune system's attack; then, the body's adaptive immune mechanism is activated, and the "battle" between the virus and the human immune system is further escalated; if the body's immune system cannot successfully eliminate the virus, the human body enters the acute symptom stage; after the acute stage, depending on the situation of the virus fighting the human body, the patient will either recover, die, or enter a long COVID period.

4. Mechanism of sequelae of COVID-19 infection

From the above introduction to the novel coronavirus infection and gastrointestinal symptoms, it can be seen that the impact of the novel coronavirus on the human body is not limited to a certain organ, nor is it limited to the ACE2 receptor. At present, the pathological process of novel coronavirus infection in the human body has not been studied clearly. The mechanism of infection process and sequelae is still just a hypothesis. It may include the following aspects.

First, after the COVID-19 infection, the human immune system will experience autoimmune disorders, which will continue to cause damage to the body. Secondly, after the COVID-19 infection, the body's inflammatory response is abnormal, and it enters a long-term chronic low-intensity inflammatory state, and the inflammatory response causes various symptoms. Third, the COVID-19 infection may not have completely eliminated the virus, which continues to affect physical health. Fourth, there are other possible mechanisms, such as post-traumatic stress disorder caused by social isolation during the COVID-19 pandemic, the blow of illness and death of relatives and friends, and fear of the virus, which subjectively feel that the body has various discomforts. It may also be because of the dysfunction of the blood-brain barrier, the damage to the intestinal barrier function, and the disorder of intestinal flora caused by the COVID-19 infection, which makes the body still have various "damages" after the acute COVID-19 infection.

In short, COVID-19 infection is a systemic disease that affects the respiratory system, but also the nervous system, cardiovascular system, and digestive system. Its infection and pathological mechanisms are complex and can cause multiple acute and long-term symptoms. Especially when the COVID-19 pandemic is not over and highly toxic variants are still likely to appear, both researchers and ordinary people should not take it lightly.

References

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