The severely neglected long-term sequelae of COVID-19 infection

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The severely neglected long-term sequelae of COVID-19 infection, Nature has continuously issued articles to raise the three most pressing issues.

The severely neglected long-term sequelae of COVID-19 infection.  According to the New York Times Epidemic Tracker, the number of confirmed cases worldwide on a single day has dropped by 25% in the past two weeks compared with the previous year. The number of new cases on June 12, 2021 is 370,000; the number of deaths has dropped by 9% compared with the previous period.

The continuous decline in the number of new cases in a single day has encouraged the reopening of countries such as the United States and Britain, and the society has immediately shown vitality.

The neglected sequelae of COVID-19

For many people, COVID-19 has become a set of numbers that fluctuate daily. People are happy to see the reduction in the number of cases and the number of new deaths.

But for many COVID-19 survivors, surviving the new coronavirus infection and being discharged from the hospital is just another long-term treatment and the beginning of a difficult life.

Because of long-term sequelae.

Correspondingly, there are currently only few and incomplete data on the long-term symptoms of COVID-19 patients. This shows a serious neglect of the long-term sequelae of COVID-19.

Nature magazine news feature published an article by Michael Marshall, exploring the most pressing issues of long-term symptoms after COVID-19 infection.

1. How many people have long-term symptoms of COVID-19?

As a biomedical researcher, we first need to determine how long the symptoms last after the new coronavirus infection is considered a long-term symptom of COVID-19.

Columbia University’s research is defined as more than 4 weeks.

Because COVID-19 is an acute viral infection, the new coronavirus with replication ability has not been isolated after 3 weeks; therefore, the symptoms after 4 weeks are no longer caused by the continuous infection of the new coronavirus.

The Office of National Statistics (ONS) also defines the long-term symptoms of COVID-19 (or sequelae of COVID-19) as 4 weeks. However, the National Bureau of Statistics of the United Kingdom followed up more than 20,000 people who tested positive for COVID-19 virus and found that even at 12 weeks, 13.7% of the people who tested positive for the COVID-19 virus still reported symptoms caused by the COVID-19 virus infection.

What needs to be confirmed is that the 13.7% ratio is based on all those who have tested positive for nucleic acid, that is, including asymptomatic infections; it is not from symptomatic COVID-19, and not from hospitalized cases. So this is a very high ratio.

The follow-up results for hospitalized patients showed even more worrying results.

In the Columbia University follow-up study of discharged patients from 38 hospitals, they evaluated the 60-day follow-up results of 1,250 discharged patients. It was found that 6.7% of patients died and 15.1% of patients needed to be re-admitted; 32.6% of patients had persistent symptoms, and 18.9% of patients had new or worsening symptoms.

In Italy, 143 discharged patients were followed up for 60 days and found that 87.4% of patients had persistent symptoms. Fatigue (53.1%), dyspnea (43.4%), arthralgia (27.3%) and chest pain (21.7%) were the most common symptoms , 55% of patients have 3 or more symptoms.

A prospective study on Wuhan, China was published in Lancet’s study on January 8, 2021. A follow-up of 1733 patients at 6 months showed that 76% of discharged patients had at least one sequelae 6 months after onset. The most common is fatigue (63%), followed by sleep disorders (26%), anxiety/depression and other psycho-neurological symptoms (23%), and 13% of patients have abnormal renal function.

Since the study by the National Bureau of Statistics of the United Kingdom is for all people infected with the new coronavirus, and the follow-up is based on community-based samples, it is considered the best study so far.

As of June 13, 2021, 175 million people worldwide have been infected with the COVID-19 virus. According to the UK National Bureau of Statistics, 13.7% of the infected people have long-term symptoms, which means that about 24 million people are still full after 3 months of infection. Suffering from symptoms of COVID-19 infection.

Women seem to be more prone to long-term symptoms than men.

In another UK National Bureau of Statistics analysis, 23% of women and 19% of men still had symptoms 5 weeks after infection.

Middle-aged people are more prone to long-term symptoms.

Among the 35-49 age group, 25.6% of people infected with the new coronavirus still have symptoms at 5 weeks, much higher than the young and the elderly. But this result is probably due to the deviation of survivors, because many elderly people infected with COVID-19 have died of illness.

Among children aged 2-11, 9.8% of those infected with the new coronavirus still have symptoms at 5 weeks.

2. Why do people with COVID-19 have long-term symptoms?

In this regard, Rachael Evants, a physician and scientist at the University of Leicester in the United Kingdom, believes that after a few weeks, the infected person has been cleared of the new coronavirus, and the long-lasting symptoms are no longer caused by continuous infection, but the sequelae of organ damage and new coronavirus infection Induced autoimmune diseases are the two keys to the long-term symptoms of COVID-19.

This view was confirmed by a Yale University article published by Nature on May 19, 2021. The study newly discovered the immunopathological mechanism of COVID-19-the production of autoantibodies. The new coronavirus infection is likely to cause a more permanent immune disorder, and persistent autoimmunity is the key reason for aggravating the disease and producing sequelae.

The analysis showed that compared with healthy controls, COVID-19 patients produced a large number of autoantibodies against immune-related proteins, including cytokines, chemokines, complement and immune cell surface proteins.

Further studies have found that these autoantibodies can inhibit the antiviral function of the immune system by interfering with the immune cell signaling pathway and the distribution of immune cells, and disrupt the immune function.

In addition, some COVID-19 patients will also produce antibodies against their own tissue antigens, and some antibodies are related to disease progression and long-lasting sequelae.

In addition to the autoimmune response induced by the new coronavirus, another important reason for the long-term symptoms of COVID-19 is the extensive organ damage caused by the new coronavirus.

Evans said: Organ damage in the acute phase will cause continuous pathological changes. Whether it can be repaired and how long it can be modified remains unknown.

In fact, the new coronavirus can not only cause serious damage to the lungs, but also affect other tissues and organs.

The article “How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes” published in Science magazine discusses how the new coronavirus attacks the main organs of the human body.

Severe lung injury

There is no doubt that the most severe damage from COVID-19 is the lungs. An Austrian study found that lung injury will decrease over time: 88% of hospitalized patients still have significant injury at 6 weeks after discharge; by 12 weeks, 56% of patients still have lung injury.

The long-term follow-up of SARS by Peking University People’s Hospital will provide some evidence for the long-term prognosis of the lungs of people infected with COVID-19. The study reported the results of follow-up of SARS hospitalized patients from 2013 to 2018. It showed that even 15 years after SARS infection, 4.6% of people still had significant changes in their lungs, and 38% had a reduced ability to spread, which meant that their lungs could not The oxygen is fully transported into the blood.

Coronavirus attacks the heart and affects blood clotting function

JAMA Cardiology published the results of a study of 416 patients with COVID-19 pneumonia in Wuhan, China on March 25, 2020, showing that 20% of patients had heart damage. In another study of 138 patients in Wuhan, 44% of patients had arrhythmia.

In addition, studies have shown that COVID-19 patients may have abnormal coagulation function. In the study of 184 ICU hospitalized COVID-19 patients in the Netherlands published in Thrombosis Research on April 10, 2020, 38% of patients had abnormal coagulation function and plaques. After falling off, it may cause pulmonary embolism or stroke.

New coronavirus causes kidney damage

The new coronavirus enters body tissues by binding to ACE2 receptors on human cells. Because kidney cells also highly express ACE2 receptors, they have become another important target of the virus.

According to a preprinted research report, 27% of 85 hospitalized patients in Wuhan suffer from renal failure. Another study showed that among nearly 200 hospitalized COVID-19 patients in and around Wuhan, 59% of the urine contained protein and blood, indicating kidney damage.

Coronavirus affects the brain

Another striking set of symptoms of COVID-19 patients is concentrated in the brain and central nervous system. Dr. Frontera said that 5% to 10% of COVID-19 patients in her hospital have neurological symptoms that require evaluation by a neurologist. “May underestimate the proportion of brain damage in COVID-19 patients”, especially because many patients use sedatives and use ventilators.

In addition to encephalitis, seizures, and “sympathetic nerve storm”, there are also strokes in patients, and many people report loss of smell.

Robert Stevens, an intensive care doctor at Johns Hopkins Medicine, said that ACE2 receptors exist in the neurocortex and brainstem, which may be the pathophysiological basis for the new coronavirus to invade the brain.

Other organs

In addition to the above-mentioned key tissues and organs, the intestines and liver are also damaged. It is often used to treat the damage caused by medication or over-stressed immune system. More COVID-19 survivors have reported abnormal blood sugar.

In this process, the proportion of patients reporting fatigue is very high.

3. How to help patients with long-term symptoms of COVID-19?

Currently, doctors have very few choices. Because people don’t know much about the long-term symptoms of COVID-19.

However, doctors in some countries have already begun to take action. The most important thing is to assess the physical condition of the COVID-19 survivors and grasp the patient’s condition.

But for people who are suffering from the sequelae of COVID-19, they just want to know “How can I get better?”

(source:internet, reference only)

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