Three men in their 30s and 40s were recently released from Hadassah University Hospital in Ein Kerem after being hospitalized there for several weeks in critical condition, hovering between life and death. The three were infected with the coronavirus several months ago and subsequently recovered. However, many weeks later, they came down with inflammation that affected many vital systems.
“They arrived in what is termed a state of shock, with very low blood pressure, and were immediately sent to the intensive care unit, where they received agents that contract blood vessels,” relates Prof. Dror Mevorach, who treated the three. The syndrome they had included renal insufficiency, liver damage and inflammation of the heart and intestines. “This was an immune dysregulation caused by COVID-19. Their immune system did not recover, and progressed to a serious inflammatory disease. The medical literature has reported very few such cases in adults, with only 11 cases around the world,” adds Mevorach.
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The period they spent ill with the virus gave no clue as to what was to come. They recovered from the initial disease fairly easily. Two of them were not even hospitalized. The third was in the hospital for a few days and then released, just like thousands of Israelis who have experienced the same progression.
A few weeks later, they were hit by something called “multisystem inflammatory syndrome [MIS] in adults,” he says. This is an adult version of something experienced by children infected with the coronavirus, similar to Kawasaki Disease, which causes coronary heart disease in children. It was first seen around the world and in Israel last April and was identified as a long-term effect of the coronavirus in children and adolescents. According to Mevorach, “there have now been hundreds of cases around the world, with dozens in Israel. It’s now being found in adults too.” He emphasizes that this is rare. “We had three cases, and I’ve heard of two in other hospitals. We’re studying and treating it, but it requires immediate hospitalization and treatment by people who know what they’re doing.”
Although this is a rare syndrome, it is but one of a raft of phenomena, grave and prolonged to various degrees. They are often undiagnosed, covered by terms such as “Long-Covid” or “Post-Covid.” As the medical and scientific communities struggle to study and characterize the immediate disease caused by contracting the COVID-19, a new phase in studying the virus is commencing. This is a complex and riveting chapter, expected to last many years, focused on learning about the long-term health impact of the coronavirus.
In any other medical situation, 10 months are insufficient for identifying and characterizing long-term effects, but in the unique case of the coronavirus epidemic, with 44 million infected people around the globe, there is ample room for recording long-term effects. Research into post-infection effects is still in its early stages, but experts can already say that such effects – with their diversity and wide range of severity – are surprisingly different than long-term effects of other viruses in the coronavirus family, or than other viral infections.
“The coronavirus has made these effects more extreme, and we can now observe things that were hard to discern earlier,” says Mevorach. “In some ways, we are relearning the immune system following this epidemic.” He says that the information gathered now is not only relevant to COVID-19. “This virus is teaching us that inflammatory conditions that we didn’t understand are probably effects that develop following some infection that has compromised the immune system. There are other viral diseases that cause various syndromes. With the coronavirus, the effects are extreme. The immune system simply goes crazy for some period.”
‘It’s unlike anything else’
The prolonged period of being sick and the phenomena that appear among people who are sick or who have recovered can be divided into three groups. The first are people whose illness lasts much longer than usual, still defining them as having COVID-19. The second group (“Long-Covid”) includes people with common and diverse symptoms that appear after they’ve recovered. These include extreme fatigue, weakness, pain, breathing difficulties and neurological and mental problems. The third group includes people with symptoms that often appear long after recovery from COVID-19. “We’re talking about MIS, hypercoagulation, pulmonary embolism or heart attacks,” says Mevorach. “These symptoms usually appear during the course of the disease, but in some cases, they show up much later, after recovery.”
Post-coronavirus illness is increasingly worrying health authorities. Some hospitals have opened clinics for people who have recovered, with a documentation of these cases and research conducted. “There are clusters of complaints reported by people who have recovered from COVID-19,” says Prof. Leonard Leibovici, who is coordinating the clinical research of the coronavirus at the Rabin Medical Center (Beilinson and Sharon hospitals). He also edits the journal Clinical Microbiology and Infection. The first cluster includes people who had moderate to severe pneumonia and continue to suffer mainly from shortness of breath. Some of these patients have lung tissue fibrosis. “We’ve been following these patients for five months and still don’t know where this is heading. We know that with previous coronaviruses – SARS and MERS – 8 to 10 percent of those affected continued to have respiratory disabilities,” says Leibovici.
Other and more common complaints relate to severe fatigue, “to the point where people can function for only two hours a day, and not always fully. They then need to lie down and end their day,” says Leibovici. “We see this in about 10 percent of people who had moderate to severe cases, with a correlation between severity of disease and the severity of later symptoms. There are other diseases with similar symptoms, such as the “kissing disease” [mononucleosis], where there are reports of fatigue and difficulties in functioning, often for up to six months. The cases in people recovering from the coronavirus are more severe, and we’re trying to understand what causes this and how to treat it.”
The arc of effects described by Leibovici and others is wide. A study at Beilinson Hospital among 500 COVID-19 patients found that 30 percent of those who had moderate to severe symptoms report continued late symptoms. “Almost 10 percent of these patients report experiencing memory and cognitive problems, with difficulty in concentrating. We are now studying this as well.” Less common are heart problems and injury to cardiac muscle, hair loss and a loss of the sense of smell and taste. This sometimes lasts after recovery. “It’s not life-endangering but it’s very disruptive, and we don’t know how long this lasts,” admits Leibovici. “Oddly, taste sometimes returns first for particular flavors.”
Dr. Jacob Ablin, head of the internal medicine and rheumatology department at Ichilov Hospital, says that “it feels like nothing else we’re familiar with.” He says a major problem he encounters with these patients is shortness of breath, even with people who had mild cases or no pneumonia, or who were not hospitalized. “You see breathlessness, no tolerance for minimal effort and a rapidly rising pulse with people who used to be very physically active. Now they can’t even do minimal exercise,” he says. “Fatigue is also very common, along with sleep problems, mainly with people who were not hospitalized. These are young people who were home with COVID-19, coming to us weeks and months later.” Ablin also describes cases of cognitive problems, muscle and back pain, as well as headaches.
Damage to the heart and blood vessels is also recognized among people who had moderate to severe cases. In some of these, the damage appears after they recover. Prof. Ran Kornowski, head of cardiology at Beilinson, says that the incidence of Post-Covid is not quite clear. There is no orderly registration of these cases. His clinic of post-recovery patients is gathering the data. So far, it appears that 10 percent of recovering patients who had moderate to severe COVID-19 show up with myocarditis, or inflamed cardiac muscle. “During their illness there were also such effects on the heart, as well as pulmonary emboli,” he says.
Children are considered to be relatively safe regarding coronavirus symptoms. According to figures released by the Health Ministry, only 500 children have been hospitalized in Israel so far, less than 1 percent of those infected. Most of them had light cases, with only a few dozen moderate or severe cases. Nevertheless, a clinic for recovering children is scheduled to open next month at Schneider Hospital in Petah Tikva. It will study similar long-term effects in children recovering from the disease.