Abstract: The new variant strains OF Omikron subtypes BA.1 and BA.2 have successively dominated the global epidemic, and now the recombinant variant of the two XE has emerged, which is 10% more contagious than the previous BA.1 and BA.2. Under the combined effect of the general increase in the effectiveness of the new crown vaccine and natural immunity, and the emergence of drugs and therapy delays, the severe illness and case fatality rates have been significantly reduced. However, what cannot be ignored is the sequelae brought about by the recovery of the new crown, what are the sequelae, how long it can last, and whether the patient can be cured. The Lancet, the world's authoritative medical journal, has published an article saying that the long-term symptoms of the new crown may be the number one challenge of modern medicine.
The long-term symptoms of the new crown refer to the sequelae of the new crown. According to the clinical case definition published by the World Health Organization in October 2021, sequelae of COVID-19 usually occur within 3 months of the onset of COVID-19 infection, with symptoms lasting at least 2 months and cannot be explained by other diagnoses [1]. This standardized definition will help clinicians more easily identify patients and provide them with appropriate care. After recovering from COVID-19 infection, what are the sequelae? Below we have taken stock of the seven possible sequelae of COVID-19 after infection.
One of the sequelae of covid-19: diabetes
Diabetes may be one of the more difficult covid-19 sequelae, and research has been conducted earlier, and a recent scientific study confirmed this possibility with data. A study titled "Risk and burdens of incident diabetes in long COVID: a cohort study," published in the top journal The Lancet Diabetes & Endocrinology, analyzed data from more than 181,000 COVID-19 patients and found that COVID-19 infection increased their risk of developing diabetes by nearly 40%[2]. About 2 out of every 100 people infected with COVID-19 develop diabetes.
Figure 1 Research results (Source: [2])
The study included 181,280 COVID-19 subjects, while the control group included 4.12 million subjects as "current controls" (followed up to 20 December 2021) and 4.287 million subjects as "historical controls" (followed up to 30 September 2019), all of whom had not had diabetes prior to inclusion in the study cohort. After statistical analysis, the researchers came to the following conclusions:
1. Compared with the current control group, the risk of diabetes in the later stage of the new crown infection increased by 40%, the risk of using hypoglycemic drugs increased significantly to 85%, and the comprehensive risk of diabetes or the need to use hypoglycemic drugs in the new crown infected people increased by 46% (18.03 cases/1000 people increased in 12 months);
2. As the acute stage of new crown infection becomes more serious, the risk of diabetes and taking hypoglycemic drugs in infected people gradually increases;
3. Black people over the age of 65, people with cardiovascular disease and pre-diabetes with a BMI of >25 are at greater risk of diabetes and taking hypoglycemic drugs after infection with covid-19.
Figure 2 Risk of diabetes among COVID-19-infected people compared to the current control group (Source: [2])
In response, the researchers said: "The current evidence shows that diabetes is an aspect of the long-term syndrome of the new crown, and the care strategy of patients with new crown infection should include the identification and management of diabetes." ”
The second sequelae of COVID-19: brain atrophy
A study published in Nature titled "SARS-CoV-2 is associated with changes in brain structure in UK Biobank" shows that the coronavirus causes the brain volume to shrink in patients, and the atrophied brain tissue is related to cognitive function and olfactory function [3].
Figure 3 Research results (Source: Nature)
The researchers, who studied 785 participants in the UK Biobank, 401 of whom contracted the coronavirus between brain scans, compared the brain images of 785 participants and found:
1. The degree of brain gray matter reduction and tissue damage in new crown infected people is greater than that of natural aging;
2. The additional loss of the brain of the new crown infected person is 0.7%, of which the damage rate of the parahipocampal gyrus and the primary olfactory cortex reaches 1.3%-1.8%;
3. Compared with the control group, the overall brain volume of the new crown infected people decreased by 0.2%-2%.
And, through the "wiring test", the researchers found that the performance and cognitive ability of the new crown infected people were poor compared with the control group, so they believed that the decline in the ability to perform and cognitive ability of the new crown infection may be related to the loss of gray matter in specific areas of their brains. The researchers said that the damage of the new crown virus to the relevant functions of the human brain is equivalent to aging patients by 1 to 10 years in advance.
Sequelae of COVID-19 No. 3: Male dysfunction
In May 2021, The World Journal of Men's Health featured "COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the." The Human Penis study mentions that vascular dysfunction or endothelial dysfunction due to COVID-19 infection may cause erectile dysfunction (ED) in men [4].
Figure 4 Research findings (Source: The World Journal of Men's Health)
The researchers collected the penile tissue of two male COVID-19 infected people, and at the same time collected the penile tissue of two men who had not been infected with covid-19 as a control group, and microscopic observation of these penile tissues showed that:
1. There are extracellular virus particles with a diameter of about 100 nm near the penile vascular endothelial cells of the new crown infected person, while the control group does not;
2. PCR shows the presence of viral RNA in penile tissue specimens of patients who are positive for new crown;
3. Compared with men who are not infected with new crown, men infected with new crown have decreased expression of eNOS in the cavernosum of the penis, which is consistent with endothelial dysfunction.
This study shows that the virus COVID-19 is present in the penis of male patients after infection with the new crown virus, and that extensive endothelial cell disorders caused by viral infections can lead to erectile dysfunction.
Published in Clinical Infectious Diseases in February 2022 titled "SARS-CoV-2 infections by intranasal or testicular inoculation induces testicular damage preventable by vaccination in golden Syrian hamsters" studies have shown that even if it is mild, the new crown virus can lead to acute testicular injury and chronic asymmetric testicular atrophy, and suggests that vaccination can prevent this complication [5].
Figure 5 Research findings (Source: Clinical Infectious Diseases)
The researchers found that:
1. After 4-7 days of nasal infection with the new crown virus, the hamster has a sharp decrease in sperm count and serum testosterone, and the size and weight of the testicles are reduced;
2. With the increase of virus inoculation, acute histopathological injury occurs in the testicles of hamsters, accompanied by different degrees of inflammation, bleeding and necrosis, and the degeneration of spermatic tubules and the interruption of sperm production;
3. Vaccination can effectively protect the testicles of hamsters from SARS-CoV-2 infection.
The above studies show that the new crown virus will cause some damage to the testicles of men, resulting in dysfunction in men, but if it can be vaccinated in time, it may reduce this damage.
The fourth sequelae of the new crown: dry eye
A team from the Department of Ophthalmology and Visual Science at the University of Chinese School of Medicine in Hong Kong found that one in five covid-19 survivors developed at least one symptom associated with dry eye, such as blurred vision, itchy eyes, pain or burning sensations. In addition, studies have found that the more severe a patient's condition, the higher the risk of developing dry eye syndrome [6]. The findings were published in Clinical and Experimental Ophthalmology under the title "Ocular surface disturbance in patients after acute COVID-19."
Figure 6 Research results (Source: Clinical and Experimental Ophthalmology)
In the study, CUHK researchers included 228 people who had recovered from COVID-19 infection and 109 healthy participants and conducted a comprehensive ophthalmic assessment and examination, including "Meibomian gland dysfunction examination" (the most common cause of dry eye disease) and "corneal fluorescein staining test" (indicator of dry eye severity). After a comprehensive analysis of the test scores of all participants, the researchers concluded that those who had recovered from COVID-19 had a significantly higher risk of dry eye-related symptoms than the general healthy population, and that patients with a higher viral load in the body had an increased risk of dry eye-related ocular symptoms by about 10 percent. Based on this, the researchers said that for anyone infected with the new crown, dry eye evaluation should be considered within 1-3 months after discharge. It is worth mentioning that the researchers pointed out that vaccination is the most important and effective measure at present, which can significantly reduce the viral load after infection, reduce the chance of infected people developing severe disease, and effectively prevent the appearance of ocular symptoms and other sequelae after the new crown.
The fifth sequelae of the new crown: cardiovascular disease
In a large study published in Nature Medicine, researchers analyzed the risk of cardiovascular disease in patients 12 months after COVID-19 infection, and the results showed that after contracting the new crown virus, there was an increased long-term risk of cardiovascular disease in 20 types, and even those with mild infections had an increased risk of cardiovascular disease [7].
Figure 7 Research results (Source: Nature Medicine)
The researchers used the U.S. Department of Veterans Affairs National Health Care Database to build a cohort of 153,760 COVID-19 patients. At the same time, two control groups were also set up, one was the contemporary control group since the outbreak of the new crown, including 5637647 uninfected people, and the other was the historical control group before the new crown outbreak, including 5859411 uninfected people. The results show that within one year after infection with COVID-19, the risk of cardiovascular diseases in covid-19 infected people increases significantly, including cerebrovascular disease, arrhythmia, inflammatory heart disease, ischemic and non-ischemic heart disease, thromboembolic disease, MACE infarction, etc. Specifically, covid-19 patients had a 52 percent increased risk of stroke, a 69 percent increased risk of arrhythmia, a 66 percent increased risk of inflammatory heart disease, and a 72 percent increased risk of heart failure [7]. Moreover, the more severe the disease in the acute phase of the new crown infection, the higher the risk of cardiovascular disease in the infected person. In response, the researchers say governments and health systems around the world should be prepared to deal with the significant impact of the COVID-19 pandemic that could lead to an increased burden of cardiovascular disease.
The sixth sequelae of the new crown: the failure of smell and taste
A study published in Science Translational Medicine is the first to analyze the impact of COVID-19 on the human olfactory system. Researchers detected persistent SARS-CoV-2 virus particles in the olfactory mucosa of patients with persistent loss of smell, suggesting that long-term recurrent olfactory loss in patients with COVID-19 may be due to persistent viral infection [8].
Figure 8 Research results (Source: Science Translational Medicine)
The researchers conducted virological, molecular and cellular studies on the olfactory neural epithelium of 7 patients with olfactory loss of smell and found that the olfactory neural epithelium is the main site of viral infection, and viral replication in this area is associated with local inflammation. The researchers believe that the persistence of viruses in the olfactory neuroepithelium and associated inflammation may be the cause of prolonged or recurrent COVID-19 symptoms, such as loss of smell, and that effective management of this disease should be considered.
A research paper titled "The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste" published in Nature Genetics earlier this year was reported.
Figure 9 Research results (Source: Nature Genetics)
This study sheds light on genetic risk factors for patients to experience loss of taste or smell after contracting COVID-19. Through an online survey, the researchers collected data on 69,841 people who developed COVID-19-related symptoms of taste or loss of smell. After conducting multiple genome association studies, the researchers identified an important genome-wide site, rs7688383, near the UGT2A1 and UGT2A2 genes, whose transition to C toT increased the likelihood of individuals losing their sense of taste or smell after contracting the coronavirus [9].
Supplements: UGT2A1 and UGT2A2, both genes expressed in the olfactory epithelium and play an important role in odor metabolism.
Covid-19 Sequelae No. 7: Mental Illness
In early March, the World Health Organization stated that the global incidence of anxiety and depression had increased significantly by 25% in the first year of the COVID-19 pandemic, and the WHO Director-General stated that "the information we now have on the impact of covid-19 on the mental health of the world's population is only the tip of the iceberg" [10]. According to a 2020 report published in The Lancet, 18% of COVID-19 patients developed mental health problems such as depression, anxiety or dementia within 3 months of being diagnosed. People living with COVID-19 are at doubled risk of mental problems compared to those who are not infected with COVID-19, and these patients typically develop post-traumatic Stress Disorder (PTSD) [11].
A study published in The Lancet Psychiatry found that about one-third of people infected with COVID-19 are diagnosed with a psychiatric or neurological disorder within 6 months of infection. After diagnostic analysis of 236379 covid-19 infected patients, the results showed that the estimated incidence of neurological or psychiatric diagnosis in patients with COVID-19 within 6 months after infection was 33.62%, of which 12.84% of patients were initial diagnoses, and for patients who had been admitted to ITU, the incidence rate was 46.42%. Moreover, 17.39% of patients were diagnosed with anxiety disorders. Overall, nearly one-third of COVID-19 survivors develop mental health or neurological-related disorders within six months of infection [13].
Figure 10 Research results (Source: The Lancet Psychiatry)
In fact, the possible sequelae of the new crown virus should be far from the above mentioned ones. In August 2021, The Lancet, an internationally renowned medical journal, published a study on the sequelae of domestic COVID-19 patients, assessing the health status of 1276 COVID-19 patients who had been hospitalized in Wuhan Jinyintan Hospital in early 2020 within 12 months after discharge. Studies have shown that after 12 months of discharge, 30% of these patients have difficulty breathing, 26% have depression and anxiety, and patients have sequelae such as muscle weakness, tiredness, sleep difficulties, hair loss, and joint pain. The coronavirus may even do more harm to the human body than we currently know. For now, vaccination to prevent infection is the best way to protect yourself.
Because of the chronic nature of these diseases, they can have long-term effects on patients and health systems, as well as on economic productivity and human life expectancy. Therefore, addressing the challenges posed by the long-term COVID-19 era requires a global long-term response strategy. In the face of the new crown virus, we must not only pay attention to the reduction of the infection rate and the severe disease rate, but also pay attention to the risk of other diseases that the new crown infection may face after recovery, including physical and psychological diseases. Nowadays, a new round of large-scale epidemic is still raging madly, and I hope that the public can improve their awareness of protection, actively vaccinate, and cooperate with community organizations to win the battle against the epidemic!
Written by | Muzijiu
Typography | Qiao Weijun
End
Resources:
[1]https://www.who.int/zh/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---7-october-2021
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[5] Li C, Ye Z, Zhang AJ, et al . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by intranasal or testicular inoculation induces testicular damage preventable by vaccination in golden Syrian hamsters. Clin Infect Dis. 2022 Feb 18:ciac142. doi: 10.1093/cid/ciac142. Epub ahead of print. PMID: 35178548; PMCID: PMC8903466.
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[7] Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022 Mar;28(3):583-590. doi: 10.1038/s41591-022-01689-3. Epub 2022 Feb 7. PMID: 35132265.
[8] de Melo GD, Lazarini F, Levallois S, et al. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med. 2021 Jun 2;13(596):eabf8396. doi: 10.1126/scitranslmed.abf8396. Epub 2021 May 3. PMID: 33941622; PMCID: PMC8158965.
[10] https://news.un.org/zh/story/2022/03/1100042
[11] People with long-lasting COVID-19 are more susceptible to mental illness. https://www.caipa.com/wp-content/uploads/2021/06/%e6%96%b0%e5%86%a0%e7%97%85%e6%af%92%e6%8c%81%e4%b9%85%e7%97%87%e6%82%a3%e8%80%85%e6%9b%b4%e6%98%93%e6%82%a3%e7%b2%be%e7%a5%9e%e7%96%be%e7%97%85.pdf
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