The new coronavirus that has infected millions of people around the world can wreak havoc far beyond the lungs. Some of the symptoms of the disease it causes, COVID-19, are quite predictable: cough, fever, chills, headache. But the effects of the pathogen don’t stop there at all. The virus can cause problems in almost every organ, including brain, heart, kidneys, gastrointestinal tract and skin.
Doctors have been surprised by what they now call silent hypoxia, or happy hypoxia, a phenomenon in which people with dangerously low blood oxygen levels are not surprisingly struggling to breathe. And there is “COVID tip, “Painful swellings on the skin called chilblains rare cases, children – previously thought to be relatively spared from a serious illness – exhibit symptoms similar to Kawasaki disease, which leads to inflammation of blood vessels throughout the body. Complications associated with blood clots, eg shots is pulmonary embolisms (also blockages of blood vessels in the lungs). “Interestingly, a respiratory virus will cause such a diverse range of clinical sequelae,” he says Peter Hotez, dean of the National School of Tropical Medicine of Baylor College of Medicine.
One of the reasons for the unusual manifestations of COVID-19 could simply be the over four million confirmed cases of a completely new disease worldwide. Some of these symptoms appeared during other viral infections, for example researchers have seen blood clots in some patients infected with original SARS coronavirus and the H1N1 flu virus. “There are now so many cases in the world that we could collect minor variants,” he says Stanley Perlman, professor of microbiology and immunology at the University of Iowa. “It makes you wonder, if in other infections, you look at two [million] to three million [cases], how many of these types of events could occur. Or it is [the situation] really special for COVID-19? “
Scientists are still trying to pinpoint the exact mechanism behind the wide range of complications. However, there appear to be two main suspects. The first is the immune system’s defensive inflammatory response to foreign invaders such as viruses and bacteria. This reaction, in turn, can lead to the second culprit: blood clotting. The impact of the disease on blood vascularization appears to underlie some of the most disconcerting effects that COVID-19 patients encounter.
Reports of coagulation-related complications such as pulmonary embolism and stroke among COVID-19 patients in intensive care units come from several countries, including China, France, Italy and the WE. The overall frequency of these problems remains unclear, but some evaluations suggest that they appear in as many cases 30 percent of critically ill patients. In rare cases, the shots have to show up in people between 30 and 40, alarming doctors.
“We are experiencing many clotting abnormalities” in ICU patients, he says Margaret Pisani, associate professor specializing in lung medicine and intensive care at the Yale School of Medicine. “We have seen strokes, myocardial infarctions, pulmonary embolisms, clots in places that we normally don’t see in otherwise healthy people who enter with a viral infection.”
Coagulation problems are not specific to COVID-19, he says Yvonne Maldonado, a professor of pediatric infectious diseases at Stanford University. A condition known as disseminated intravascular coagulation, in which abnormal coagulation occurs in all blood vessels previously reported in patients with infectious diseases suffering from sepsis (a potentially lethal immune response to an infection). “What is unusual here is that it seems to happen with this disease more often than with other diseases,” he says.
In addition to clots in the large blood vessels, researchers have reported clotting inside smaller blood vessels known as capillaries. COVID-19 “is a vascular problem,” he says Frank Ruschitzka, cardiologist at the university hospital in Zurich. “The lung is the main battleground, but it is a disease of the blood vessels.”
Scientists have not yet identified the cause of the clotting. Inflammation appears to be a likely culprit, however. The researchers discovered, for example, the presence of complement proteins—Molecules involved in the activation of the immune response – inside coagulated blood vessels. Through many of the numerous symptoms of COVID-19, the common mechanism appears to be inflammation of the endothelium, the layer of cells that make up the inner lining of the blood vessels, he says Luciano Gattinoni, visiting professor in the departments of anesthesia and intensive care at the University Medical Center of Göttingen in Germany. “Since the endothelium is present everywhere, you can explain why the symptoms are so different.”
Some of the mysterious symptoms associated with COVID-19 begin to make sense when viewed as manifestations of a vascular disorder. Take silent hypoxia, a condition that Gattinoni has attracted attention in recent weeks as unrelated to lung oxygen capacity but rather to altered blood flow through the organ.
Many other strange manifestations of COVID-19, including the kidney problems requiring dialysis (in some cases, clotted blood has reported clogged up filters in dialysis machines) chilblains in the toes and Kawasaki-like symptoms in children have also been associated with vascular complications. “This is a rapidly changing field, but the vascular component of the disease is obvious,” says Ruschitzka, although he warns that “there is never a single mechanism.”
Whether the vascular problems associated with COVID-19 result from direct effects of the virus or from the body’s immune response remains an open question. Some evidence suggests that SARS-CoV-2, the coronavirus behind COVID-19, can attack endothelial cells directly. In April Ruschitzka and his colleagues published a document that told three autopsies in the Hand which found the presence of viral particles in the endothelium of the kidneys and an accumulation of inflammatory immune cells within the endothelium of various organs, including the kidney, heart and lungs. Ruschitzka, however, says that the body’s immune response, not the virus itself, is the most likely explanation for excessive clotting. “What we see everywhere is pronounced inflammation,” he adds.
However, it is too early to rule out the direct effects of the virus. “There are many conditions that cause inflammation where these types of clotting disorders are not seen,” says Hotez, increasing the prospect that the virus may be directly involved in stimulating blood abnormalities. The diversity of symptoms, he suggests, may have something to do with the ACE2 receptors to which SARS-CoV-2 binds. These receptors are present on cell surfaces multiple organs affected by COVID-19.
Alex Richter, an immunologist at the University of Birmingham in England, notes that the timing of a symptom may suggest whether it is caused by the virus itself or by the body’s immune response to it. A frequent early symptom – loss of taste and smell – can probably be a direct effect of the virus compared to clotting complications or Kawasaki-like symptoms that appear later. “There is almost a timeline on how we are experiencing these symptoms and on the likelihood that they will have a direct effect on the virus or because of a hyperimmune response,” he says.
Richter notes that what is particularly strange about the Kawasaki-like symptoms observed in children is that they appear to appear several weeks after initial exposure to the virus. She and her team are currently studying samples from affected children to find out how the immune system could generate these effects. So far, they have found evidence that these individuals have antibodies that suggest a well-developed immune response, indicating that the infection probably occurred weeks before symptoms started. Richter states that this observation is distinct from what has been seen in adult cases, where the immune system seems to react much more immediately to the infection.
Despite the wide range of COVID-19 symptoms, the emerging understanding of the infection suggests a number of common underlying factors that may be at work. “It could be that there are actually just a few things going on and, depending on where they come from, you see all these different symptoms,” says Perlman. “So the question is, why does it manifest itself differently in different people?” Most people infected with SARS-CoV-2 will not have to be hospitalized in intensive care, but those who are hospitalized face a disease that continues to hold surprises for the medical community. Clear risk factors portend serious diseases, including age, obesity and heart conditions. But Scientists are still looking for inflammatory biomarkers and other biochemical signals to help doctors predict who will improve on their own and who will become seriously ill, Maldonado says, adding: “Everyone is trying to understand it.”