Recently, the "Lancet" published a study on the sequelae of COVID-19 patients (also known as "long-term COVID-19"), which once again woke up the alarm about the long-term impact of the COVID-19 epidemic on humans.
This authoritative medical journal has specially distributed an editorial for this, pointing out that as the COVID-19 pneumonia pandemic continues, symptoms such as persistent fatigue, dyspnea, and depression may affect millions of people, but what people know about this situation Very little.
What are the long-term effects of the COVID-19 virus? What are the characteristics, severity, and duration of these symptoms? There have been no clear answers to these questions for a long time, and this study gives the latest data on the sequelae of COVID-19.
Still unable to fully recover after 1 year
The study released by The Lancet on August 28 tracked 1,276 COVID-19 patients discharged from Wuhan Jinyintan Hospital and followed up their health and quality of life 6 months and 12 months after they were discharged from the hospital. A study on their recovery was conducted.
The research was led by Cao Bin from the Department of Respiratory and Critical Care Medicine of the China-Japan Friendship Hospital, Wang Xianguang from Wuhan Jinyintan Hospital, and Wang Jianwei from the National Respiratory Medicine Center and the Chinese Academy of Medical Sciences.
Cao Bin’s team published in The Lancet in January this year the follow-up of the same group of patients when they were discharged from the hospital for 6 months. At that time, they found that about three-quarters of COVID-19 survivors still had "fatigue or muscles" after they were discharged from the hospital. At least one persistent symptom such as "weakness". Patients who are critically ill during hospitalization are more likely to have pulmonary gas diffusion disorders and imaging abnormalities than patients with lower disease severity.
In this study, the research team counted all patients discharged from Jinyintan Hospital from January 7 to May 29, 2020, a total of 2,469 people. Among them, 1,193 patients were excluded from the study for many reasons, including death after discharge, living in a nursing home or welfare home, suffering from dementia or mental illness, and suffering from osteoarthropathy. The last 1276 patients were included in the study, and two follow-ups were completed 6 months after discharge and 12 months after discharge.
The median age of these patients was 59 years old, 864 patients received oxygen through nasal catheters and masks during hospitalization, 94 required high-flow nasal oxygen therapy or non-invasive ventilation, invasive mechanical ventilation, and 54 patients had been admitted to the ICU.
It can be seen that most of the patients are severe and critical cases. During hospitalization, these patients received treatment including corticosteroids, antiviral drugs, lopinavir, abidol, chloroquine phosphate, hydroxychloroquine, antibiotics, intravenous immunoglobulin, etc.
In the two follow-up visits, the patients received detailed face-to-face interviews, physical examinations, and 6-minute walk tests. They also completed a series of questionnaires to reflect their respiratory status, quality of life, medical treatment after discharge, and work. Condition and so on. According to the severity of the patients, the researchers randomly sampled their lung function and chest CT at 6 months after they were discharged from the hospital. At 12 months after they were discharged from the hospital, some people were further reviewed as needed.
In addition, the researchers also recruited community adults from Wuhan who had not been infected with COVID-19 as a control group. COVID-19 survivors and the control group were further matched 1:1 by age, gender and underlying disease. Because of the long span and large sample size, this study is considered to be the largest study of COVID-19 survivors to date.
The results of the study show that most COVID-19 patients have recovered well over time after being discharged from the hospital, and have resumed their original work and life, but their current health status is still lower than that of the control population.
Sleep disorders, hair loss, taste and smell disorders, headaches, joint pain, anxiety or depression... these symptoms are all included in the study as sequelae of COVID-19.
Compared with the 6 months after discharge, some of the sequelae disappeared significantly over time at 1 year. The proportion of people with at least one sequelae symptom also dropped from 68% at 6 months to 49% at 12 months. Similar to SARS sequelae, "fatigue or muscle weakness" is also the most common symptom of COVID-19 patients. The proportion of patients with this symptom has dropped from 52% at 6 months to 20% at 12 months.
However, the causes and pathogenesis of fatigue and muscle weakness after COVID-19 infection are still unclear. Based on some previous studies of SARS, impairment of lung diffusion, muscle inflammation caused by virus at the onset of disease, cytokine disorders, muscle atrophy and degeneration, corticosteroid myopathy, or a combination of these factors, may all be triggers.
In contrast to the above-mentioned decline in symptoms, the proportion of COVID-19 patients with dyspnea, anxiety and depression after 12 months of discharge was higher than that of six months ago. The proportion of dyspnea increased slightly from 26% at half a year to 30% at 12 months. Over a period of up to 12 months, approximately 20%-30% of moderate patients have observed pulmonary diffusion disorders, and this proportion is as high as 54% of critically ill patients. In addition, more patients presented with anxiety or depression (26%) 12 months after discharge from the hospital, compared with 23% at 6 months after discharge.
"Maybe these people themselves have some chronic diseases. Therefore, it is not clear that these symptoms of breathing difficulties are caused by lung injury when infected with COVID-19." Jin Dongyan, a professor at the School of Biomedical Sciences of the University of Hong Kong and a virologist, told China News Weekly.
The article analyzes that chronic or late-onset psychological symptoms after COVID-19 infection are likely to be directly affected by the virus infection, or it may be due to the body's abnormal immune response, excessive activation of the immune system or autoimmune response. In addition, reduced social contact, loneliness, incomplete physical recovery, and unemployment may also affect the mental symptoms of patients.
In Jin Dongyan's view, although based on large-scale sample statistics, the scope of the sequelae of COVID-19 is somewhat broad. He said, after all, social discrimination and the patients themselves being too worried about the body may cause symptoms of depression and insomnia, rather than symptoms directly caused by the COVID-19 virus infection.
He believes that among the sequelae of these 1276 patients, which are caused by the COVID-19 virus, which are caused by the treatment drugs, and which are caused by psychological and spiritual problems, these problems still need to be further explored.
Not only cause pneumonia
According to the clinical definition, sequelae refer to "symptoms such as organ defects or dysfunction left after the disease has recovered." It is said that various physical and mental symptoms that occur after being infected with COVID-19 for more than 4 weeks and cannot be explained by other diagnoses can be called sequelae of COVID-19.
In Jin Dongyan's view, the current scientific community has no specific conclusion on the sequelae of COVID-19. "The sequelae of COVID-19 is not a simple disease, but should be regarded as a mixture of multiple symptoms."
In the eyes of most people, the COVID-19 virus is a respiratory virus that mainly attacks the lungs. However, more and more evidences show that after being infected with the COVID-19 virus, many symptoms have spread to organs outside the lungs. In other words, COVID-19 infection does not only cause pneumonia.
At the online "2020 Lancet-Chinese Academy of Medical Sciences Conference on Medicine and Health", Cao Bin, director of the Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, pointed out that the main pathogenic mechanism of COVID-19 pneumonia is directly caused by the virus itself. Cell death and viral infection lead to an imbalance in the immune response, which can cause secondary damage to the organ.
He said, “In the early severe cases in Wuhan, many cases showed multiple organ dysfunction, such as acute respiratory distress syndrome, metabolic acidosis, internal environmental disorders, acute kidney injury, liver injury, thromboembolic events, cardiac Injury, and even clinical manifestations of neurology."
In April this year, the “New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Eighth Edition Revised Edition)” issued by the National Health Commission showed that the pathological changes caused by COVID-19 pneumonia involve not only the lungs, but also the spleen, hilar lymph nodes and bone marrow. , Heart and blood vessels, liver and gallbladder, kidneys and other organs.
In July, a study by The Lancet showed that through feedback from 3762 people with confirmed or suspected COVID-19 infection from 56 countries, researchers collected more than 200 types of "long-term COVID-19" from 10 organ systems. symptom.
A 7-month follow-up survey of 66 symptoms of these patients found that most of the interviewees took more than 35 weeks to recover. Among all the more than 200 symptoms, these patients experienced an average of 55.9 symptoms, involving 9.1 organ systems. After 6 months, more than 50% of the survivors developed symptoms such as fatigue and cognitive dysfunction.
In addition to multiple organs and multiple symptoms, the range of people affected by the sequelae of COVID-19 is also expanding.
In a congressional hearing in April this year, Dr. Francis Collins, director of the National Institutes of Health, cited a study that showed that 11%-15% of infected young people may "eventually develop this long-term sequelae."
Affect the nervous system?
It is worth noting that many studies have mentioned the sequelae of the nervous system.
The nervous system is divided into the central nervous system and the peripheral nervous system. Sun Yongan, chief physician of the Department of Neurology at Peking University First Hospital, pointed out that the decreased sense of smell and taste in the early stages of infection is actually caused by damage to the peripheral nervous system. When the human body's resistance is reduced or the blood-brain barrier is destroyed, the central nervous system will also face the situation of being "breakthrough" by the virus.
Sun Yongan said that if the virus is detected in the cerebrospinal fluid, it can theoretically be considered that the virus may invade the central nervous system. In his view, it is more common for the virus to invade the nervous system. With long-term observation of COVID-19 survivors, there should be more evidence in the future.
In fact, many studies have confirmed that this "breakthrough" has traces to follow.
In March 2020, Wang Guiqiang, a member of the National Medical Expert Group and Director of the Department of Infectious Diseases of Peking University First Hospital, once introduced that a critically ill patient with COVID-19 pneumonia experienced convulsions and disturbance of consciousness during the treatment process, as well as central nervous system involvement. Performance. The doctor found the nucleic acid of the new coronavirus in the cerebrospinal fluid of this patient, suggesting that this virus may be the cause of central nervous system involvement.
However, Wang Guiqiang believes that the overall probability of COVID-19 virus invading the nervous system is not particularly high, because it needs to enter the blood circulation and also needs to break through the blood-brain barrier.
In August 2020, the University of Hong Kong and other units jointly published a paper in Cell Research, which pointed out that the COVID-19 virus can directly infect the nervous system, and can also infect cortical neurons and neural progenitor cells in the human brain. .
Sun Yongan believes that the impact of the COVID-19 virus on people is systemic and may affect different organs. Among them, the pathological changes of the central nervous system are not necessarily primary, but may be secondary reactions caused by other complications. For example, after infection with the COVID-19 virus, symptoms of ischemia and hypoxia caused by complications of the heart, lungs or other organs may have an impact on the human nervous system.
In a live sharing session at the beginning of this year, Cao Bin said, “We cannot treat COVID-19 virus infection as an acute disease.” He suggested that special attention should be paid to the chronic effects of acute virus infection on the body, and not just Rehabilitation of lung function is limited, but diagnosis and treatment thinking should be expanded. For example, thrombosis prevention, heart and central nervous function rehabilitation also need attention, and more scientific research is also needed to reveal the underlying mechanism.
So, what factors may cause the sequelae of COVID-19? Some recent studies have given possible answers.
On September 2, according to media reports such as USA Today, one possible explanation for the kidney damage caused by the COVID-19 virus is that the COVID-19 virus excessively activates the immune system in a way that damages the body's organs. Recently, another study published in the "Journal of Thrombosis and Hemostasis" pointed out that new evidence suggests that blood clotting may be the root cause of "long-term COVID-19."
There are also some speculations that the sequelae of COVID-19 may also be caused by: First, the virus or fragments of it continue to cause severe damage in the body; second, the body needs to heal after fighting the COVID-19 virus, and various discomforts are only the healing process. One part; the third is that because the COVID-19 virus is a new virus for humans, it may cause the immune system to overreact for a long time.
Many experts and medical figures told China News Weekly that for now, the COVID-19 virus infection does produce symptoms of varying degrees, but the specific cause is still unclear.
Wang Jianwei, a professor at the Institute of Pathogenic Biology of the Chinese Academy of Medical Sciences, said in a meeting earlier this year that many questions about the changes and effects of antibodies in COVID-19 patients after discharge from the hospital still need to be further studied, including which immune response is responsible for antiviral immunity. The decisive role is what other immune protection mechanisms besides neutralizing antibodies and how high the level of antibodies can provide adequate protection.
In his opinion, after the level of neutralizing antibodies in the patient's body decreases, whether they are at risk of re-infection with the COVID-19 virus, and how long it will take to re-infect them, these questions are still unanswered.
How to deal with the sequelae of COVID-19
Cao Bin’s team and other research groups recently published a one-year follow-up study in The Lancet. They also mentioned the impact of COVID-19 pneumonia on the work of survivors. There were 479 patients who had work before the illness. Among them, 57 (12%) failed to resume their original jobs: 32% of them were due to decline in physical function, 25% were unwilling to do their previous jobs, and 18% were dismissed.
It is more common in the literature that 10%-30% of COVID-19 patients have sequelae. According to the current estimate of nearly 90,000 cured and discharged cases in China, at least nearly 10,000 people will face the sequelae of COVID-19.
"Many of them hope that the entire group of COVID-19 survivors will be noticed, but they do not want individuals to be noticed. Individuals often choose to'hide' and are unwilling to place themselves where others can see." An industry insider who had communicated with many patients told China News Weekly.
"Mr. A Yuan", an excellent answerer on medical topics, told China News Weekly, "Many COVID-19 survivors are concerned about these long-term symptoms, but they lack professional rehabilitation guidance." "Mr. A Yuan" believes that Professionals pay attention to this group, and existing medical institutions should think about how to help this group perform effective recovery, such as timely psychological intervention and physical function recovery guidance for people recovering from COVID-19.
Cao Bin once pointed out that first of all, when medical staff are treating COVID-19 patients, they should take into account the mid- to long-term adverse reactions that may occur after these patients are discharged from the hospital, and the protection of vital organs should be done more meticulously. Secondly, for patients who have been discharged, even if they are dischargedAppropriate symptoms, and adequate health education should be done, because after 3 months or 6 months of discharge from the hospital, patients may still have various symptoms.
He believes that when it comes to organ protection, in addition to the protection of lung function, it is also necessary to closely monitor the function of the external organs of the lung, such as thrombosis and new-onset diabetes. If a patient suffers from renal impairment in the acute phase, doctors must be very careful when administering medicine to the patient during the recovery phase and avoid using drugs that are harmful to the kidneys.
Effectively solving the sequelae of COVID-19 is a long-term and complicated task for both patients and society as a whole.
WHO Director-General Tan Desai called on countries to give priority to understanding, rehabilitation and research on the long-term consequences of COVID-19 pneumonia, and to collect "long-term COVID-19" data. He pointed out that the scientific community and the medical community must cooperate to explore the mechanism and pathogenesis of "long-term COVID-19" and finally find an effective treatment.
Positively, this effort is already underway. Many countries and research institutions have identified "long-term COVID-19" as a priority and initiated clinical and epidemiological studies.
In February of this year, the National Institutes of Health (NIH) launched a $1.15 billion research program, which includes a prospective "long-term COVID-19" study. Some COVID-19 patients will be tracked to study their symptoms and The long-term effects of COVID-19.
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