More than just pneumonia: The new coronavirus can severely damage multiple organs and tissues

The story continues, and we are still on the road to explore the new coronavirus. We strive to understand and solve problems, and we continue to encounter new problems.

Compiled by | Sister Xian

At the end of 2019, a terrible pneumonia of unknown cause spread rapidly in Wuhan, China. At that time, hospital beds were filled with more and more patients who needed ventilators. Experts initially thought it was a simple lung disease.

Months later, when the first wave of the coronavirus pandemic hit the East Coast of the United States, clinicians expected that patients would primarily experience respiratory problems, with severe cases requiring ventilators.

But Harvard Medical School's Haytham Kaafarani, a trauma surgeon and critical care physician at Massachusetts General Hospital, and his colleagues noticed an unexpected surge in COVID-19 patients experiencing intestinal complications, including nausea, loss of appetite, and even severe intestinal obstructions, often requiring consultation with a gastrointestinal surgeon.

To date, more than 100 million people have been infected with the new coronavirus worldwide, and the number is still increasing. Among them, more than 3 million cases of death due to lung damage have occurred. However, the large number of infected people shows that the virus harms far more than the respiratory system. It can also cause systemic symptoms such as headaches and diarrhea. Today, we can be sure of one thing, that is, the new coronavirus infection does have extrapulmonary symptoms, and the new coronavirus does cause extensive damage besides the lungs-something we didn't know more than a year ago. Over the past year and a half, researchers around the world have discovered various symptoms in the blood, heart, kidneys, intestines, brain and many other parts of the body of infected people. Some studies have shown that nearly one-third of people infected with the new coronavirus will experience extrapulmonary symptoms, and in critically ill patients, this proportion can reach more than two-thirds.

In addition to revealing the damage caused by the new coronavirus in the body, patient assessments, autopsy investigations, and experiments on human cells and tissues also provide clues for us to explore the mechanisms by which these complications may arise. Single-cell sequencing analysis showed that the receptors ACE2 and TMPRSS2, which are widely present on the cell surface, help the new coronavirus enter human cells. PCR technology has found that new coronavirus RNA is present in a variety of tissues, indicating that the virus may have infected cells outside the respiratory system, although direct evidence of this infection is incomplete. Another possible cause of systemic complications is the uncontrolled immune response and coagulation caused by the infection. (Figure 1)

Figure 1. The impact of the new coronavirus on organs and tissues throughout the body. (Click to see the larger image)

Coagulation crisis

Blood clots, big and small, are one of the most common complications of COVID-19. Early in the pandemic, reports from ICU patients in countries such as China, France and Italy showed blockages in large blood vessels in the patients' lungs and legs. Some studies have shown that nearly half of critically ill patients will eventually develop blood clots. Later studies found that many new crown patients also developed blood clots in the small arteries and capillaries in the lungs and in the blood vessels of other organs such as the heart, kidneys, brain and liver. In addition, researchers have found high levels of D-dimer, a protein fragment that indicates the presence of blood clots, in patients with severe new crowns.

At present, the cause of thrombosis is still unclear. Hanny Al-Samkari, a hematologist at Massachusetts General Hospital and an assistant professor at Harvard Medical School, pointed out that using patient samples, researchers have found some clues that the new coronavirus may directly infect vascular endothelial cells and platelets (both of which are components of blood clotting) through ACE2 receptors on the cell surface. However, the coagulation process may also be caused by maladaptive and uncontrolled immune responses. In short, thrombosis is not a single event.

In addition, whether due to direct viral effects or inflammation, a major feature of COVID-19 infection is damage to the vasculature, resulting in vascular dysfunction (called endotheliopathy) that can cause clotting. Studies of various organs affected by COVID-19 have also found that endotheliopathy is a major manifestation of COVID-19 disease. For example, the heart of infected people shows major symptoms of vasculitis and endothelial cell damage and dysfunction.

As more and more COVID-19 patients have clotting problems, researchers have launched clinical trials to evaluate the therapeutic effects of blood thinners. An international collaboration has launched three such trials: REMAP-CAP, ACTIV-4, and ATTACC. But the results so far have surprised everyone. People are accustomed to thinking that bleeding and clotting are complementary "either-or" relationships, but this is not the case - interim results of the trial (including data from more than 1,000 patients in 300 hospitals around the world, which has not yet been peer-reviewed) show that blood thinners may increase the likelihood of severe bleeding in patients with COVID-19, leading to worse outcomes; but at the same time, it can reduce complications in moderately ill patients (hospitalized but not in the ICU). This shows that at least in milder cases of COVID-19, preventing thrombosis can help prevent more serious problems, but there is a threshold. When a patient's blood vessels are already damaged and full of clots, the use of blood thinners will be more likely to cause bleeding and endanger life. Of course, the observation that blood thinners can prevent the deterioration of mild COVID-19 cases also shows to some extent that an important way in which the new coronavirus causes disease may be related to coagulation.

Kidney damage

The link between COVID-19 and kidney function came to the fore early in the pandemic. As ICUs around the world began to be overwhelmed by demand, reports from around the world soon showed that patients with chronic kidney disease and those requiring dialysis or a kidney transplant were at increased risk of deterioration and death from the coronavirus.

Doctors have also found that acute kidney injury is a major complication in patients with severe COVID-19, even in those without a history of kidney disease. Some early observational studies reported that up to two-thirds of hospitalized COVID-19 patients experienced kidney-related complications, most of whom had mild to moderate symptoms (excessive levels of protein in the blood or urine indicate kidney damage). However, some patients experienced severe kidney damage and had to undergo dialysis; others had an increased likelihood of death.

Currently, scientists are still studying the mechanism by which the new coronavirus affects the kidneys. Autopsy reports show signs of coagulation, inflammation, and viral RNA in patients' renal tubules (a kidney structure that removes excess fluid, salts, and other waste from the body). Other studies have detected the new coronavirus spike protein in patients' urine, indicating that the virus may have directly infected urinary tract cells. Of course, this evidence is still in its preliminary stages, and Professor Annette Bruchfeld, a nephrologist at Linköping University in Sweden and Karolinska Institute in Sweden, believes that the direct and indirect effects of the virus will work together with susceptibility factors such as genetics.

It is not yet clear whether kidney complications associated with COVID-19 will develop into chronic conditions. While such complications can lead to death, it does not mean that if you survive, you will definitely become a chronic dialysis patient. We do not yet know what the long-term effects of concurrent kidney damage will be.

Gastrointestinal complications

In the early months of the pandemic, doctors saw early signs that COVID-19 could damage the intestines. An early meta-analysis (a research method that systematically and quantitatively analyzes previous research results) of data from more than 4,000 patients, most of whom were from China, found that the overall incidence of gastrointestinal symptoms—including loss of appetite, diarrhea, and nausea—was about 17%, and that gastrointestinal problems seemed to be more common in patients with severe COVID-19.

Kaafarani and colleagues first noticed an increase in the number of COVID-19 patients experiencing these complications at Massachusetts General Hospital last spring. They immediately launched a study to assess whether this trend was a unique manifestation of COVID-19 or a general response to critical illness. To do this, they selected COVID-19 patients admitted to the ICU in March and May 2020 and compared the rates of intestinal problems in the two patients with those admitted for acute respiratory distress syndrome (ARDS, a type of respiratory failure discovered before the outbreak.) They recorded symptoms such as intestinal blockage and ileus in these patients, as well as problems with intestinal motility. The results were shocking - the incidence of gastrointestinal complications in patients with severe COVID-19 was 74%, almost twice the rate of ARDS patients (37%) who were not infected with the new coronavirus. Such results made the researchers increasingly believe that there may be something special causing gastrointestinal complications in COVID-19 patients.

How does the new coronavirus affect the intestine? This is still an open question. But some evidence suggests that the direct effect of the virus may be partly responsible. For example, studies have found that the levels of ACE2 receptors in gastrointestinal cells of new coronavirus patients are usually high. In addition, scientists have found new coronavirus RNA in patients' feces and gastrointestinal tissue samples.

Whether the new coronavirus replicates in the gastrointestinal tract remains to be confirmed. But it is worth mentioning that scientists have detected the messenger RNA (genetic sequence string that guides the construction of proteins) of the new coronavirus in the intestines of new coronavirus patients, which seems to prove that the new coronavirus has indeed replicated in the intestines.

According to Kaafarani, preliminary examinations of gastrointestinal tissue from COVID-19 patients also showed some signs of clotting, especially in the small blood vessels below the intestine, which could impede blood flow into the intestinal arteries. At present, both clotting and direct viral effects can explain the effects of COVID-19 on the gastrointestinal tract, and I believe that in the next few years, researchers will surely find out the true cause and effect behind this.

Multi-organ disease

Studies have shown that the new coronavirus also has an impact on other parts of the body. For example, in the heart, the new coronavirus is associated with heart damage and failure; in the brain, it can cause problems such as stroke, epilepsy and sensory impairment. In addition, researchers have also found that organs such as the eyes, ears and pancreas of new coronavirus patients are also damaged.

As with problems with the vasculature, kidneys, and gastrointestinal tract, it is not yet clear whether these symptoms are caused by direct infection with the coronavirus or by indirect effects such as inflammation or coagulation. In short, to date, there is limited evidence that most organs in the body other than the lungs are directly infected by the coronavirus, so most of the damage that occurs in patients with the coronavirus is likely the result of infection rather than the effects of the virus itself.

As research continues, more and more discoveries will help guide treatments for the various symptoms of COVID-19—both the acute phase of infection and the long-term infection, about which little is known. Some of the current discoveries have led to new treatments, such as the blood thinners mentioned above, and expert guidelines have been modified accordingly.

However, there are still many unanswered questions, especially about the long-term effects of COVID-19. That’s what’s frustrating, we don’t know enough to help patients in the long run—there’s still so much we don’t know.

Compiled from:

https://www.the-scientist.com/infographics/infographic-the-havoc-sars-cov-2-wreaks-on-the-body-69111