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Spectrum of COVID-19: From Asymptomatic Organ Damage to Long COVID Syndrome

  • Keywords:
  • Asymptomatic Organ Damage
  • Long COVID syndrome
  • Reduced Functional Capacity
  • Publication date:

    Submission date:



    Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10-30% of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. 

    It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.

    This article after additional peer review at Medical Review and subsequent changes is now also published at


    Symptomatic Long COVID affects 10-30% of the COVID-19-infected population depending on what symptoms are measured. (1-3) Organ damage might affect over 50% of post-COVID-19 individuals (4-6) and perhaps more in adolescents and children. (7)

    As COVID-19 continues to transmit across the world, the consequences of the pandemic are becoming clearer. It is now known that this virus is not only contagious and potentially deadly but can cause long-term damage as well. Acute COVID-19 is known to cause a wide range of symptoms, ranging from mild to severe and life-threatening complications. Some do not develop symptoms in the acute phase at all. Others experience sudden deaths, (8) heart attacks, strokes, (9-11) debilitating systemic infections, (12-16) heart failure, new autoimmune disorders, (17-20) and more are being noticed. Increasing numbers of publications since 2020 describe the pathophysiology mechanisms behind these complications, (1, 21-27) and large case-control studies (27-31) indicate a significant increase in them. 

    Across the spectrum of acute symptoms, many still develop longer-term symptoms known as Long COVID. Estimates range from 10-30% of people who contract COVID-19 experience symptoms that last beyond the initial illness, depending largely on definition. But what is even more concerning — and less widely known — is the long-term effect that COVID-19 can have on the organs of those who were infected. 

    Recent studies have shown that well over 50% of people, for some measures 70% or more, who have contracted SARS-COV-2 suffer damage to their organs. (4-6) For example, COVID-19 has the potential to cause lasting scarring in the lungs of infected patients, resulting in reduced lung function. (32,33) It has been linked with long-term cardiovascular damage, (10,34,35) which can cause difficulties when exercising (36,37) and even increase the risk of a heart attack (9) or stroke. COVID-19 can cause brain damage including loss of brain tissue, small blood vessels, and merged brain cells. In some patients, perhaps many, there is also damage to the immune system.

    While the term Long COVID refers to a set of symptoms whose exact causes are not yet fully understood, the virus’ underlying effects on the body are an even more common and insidious aspect of many COVID-19 infections. They can lead to a range of consequences including sudden severe events, loss of quality of life or a diminished lifespan (38). Some of these effects have been recognized in the literature since 2020 and yet have been largely ignored. There are many effects resulting from COVID-19 on bodily systems. Here we discuss evidence for five of these, the heart, brain, endothelial cells and blood vessels, endocrine system, and immune system (see Figure 1). 

    Figure 1: Overview figure of effects of COVID and Long COVID on organ systems. Created with

    The Heart

    According to work published recently (39), people infected with SARS-COV-2 between March and November 2020 were shown to be at higher risk for heart attacks, coronary heart disease, heart failure, and deep vein thrombosis. In this work, they followed over 7,500 people, both with and without pre-existing heart conditions. This was pre-vaccine and pre-omicron; however, data published in May 2023 shows that after omicron, the risk is essentially as high as for alpha/delta, higher with delta and varied with the severity of infection, but still present in those who experience a mild acute infection. (40)

    The infected group was 40% more likely to develop cardiovascular disease when compared to those uninfected. This group was also five times more likely to die during the following 18 months when compared to those not reporting prior SARS-COV-2 infection. The risk of adverse outcomes, such as hospitalization or death, is significantly greater in cases of severe infection compared to mild infection. However, it is important to note that even mild infections carry a higher risk of complications and should not be taken lightly. 

    This was not a surprise as early work (41) on a cohort of 100 recovered German patients in 2020, one-third hospitalized and two-thirds recovered at home used cardiovascular magnetic imaging to show cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%). These were not dependent on preexisting conditions, disease severity and overall course of the acute illness, and time from the original diagnosis.

    Reduced blood oxygen or ischemia in the heart can cause acute myocardial infarction (AMI) and stroke. This can result from disruption of underlying chronically inflamed atherosclerotic plaques, and this has been clearly shown to be a clinical complication of COVID-19 (42, 43). It has recently been established that SARS-CoV-2 infects coronary vessels, and thereby induces inflammation of the plaques. (44) These might trigger acute cardiovascular complications, and the chance of long-term cardiovascular risk is elevated. AMI and stroke can also result from other respiratory viral infections, including influenza virus. (45). It is important to note, however, that patients with COVID-19 are seven times more likely to have a stroke than patients after influenza (46) and the risk for either AMI or stroke is still elevated up to 1 year after infection. (9) 

    The Brain

    There is now strong evidence that the SARS-COV-2 virus can enter the brain during infection leading to damage, including loss of both gray and white matter – impacting both the nerve cells and the support cells. The virus has been shown to disrupt the blood-brain barrier that protects the brain. (47) The impact of COVID-19 on the brain has been extensively studied, and some key findings have been reviewed (48-52)

    SARS-COV-2 might enter via a damaged blood-brain barrier (53,54) as SARS-COV-2 damages endothelial cells (47,54) or it might enter from the nose via a nasal nanotube mechanism. (55) Peripheral inflammation has also been shown to lead to post-infection brain deficiency, probably via the release of cytokines. (56) Inflammation of the Vagus nerve has been observed to cause dysautonomia during acute infection leading to disruption of the autonomic nervous system and affecting heartbeat, blood pressure, digestion, breathing, bladder control, dental health, etc. (57) These all can occur during the entire spectrum of illness of COVID-19 from mild to severe.

    Acute infection can lead to direct changes in the brain resulting in losses in learning/memory ability and cognition. (58,59) Significant neurologic and psychiatric outcomes of COVID-19 have been shown (60) including higher incidence of ischemic stroke, intracranial hemorrhage, dementia, and mood/anxiety disorders. Cerebral blood flow is diminished during acute COVID-19 infection. (47) The neurosymptoms of acute COVID-19 have been found to resolve in many patients, but magnetic resonance imaging has found that alterations can persist after 6 months in the amplitude of low-frequency fluctuation (ALFF) and functional connectivity in the right frontal, temporal, and occipital lobes of the brain. (61) Importantly, ALFF is a stable and reliable parameter to characterize intrinsic or spontaneous brain activity found in various brain diseases, including Parkinson’s disease, posttraumatic stress disorder, major depressive disorder, and bipolar disorder. (62) There is evidence of dopaminergic senescence with SARS-COV-2 infection which bodes poorly for a number of neurodegenerative disorders. (63) Direct invasion of the brain by SARS-COV-2 could lead to ORF3a expression, which has been shown to disrupt the autophagy-lysosomal pathway, impair sphingolipid homeostasis, and to drive neuropathogenesis including the accumulation of α-synuclein. (64)

    These acute and short-term remaining conditions are worrisome, but there are now a number of studies that suggest that SARS-COV-2 is causing longer-term damage via protein changes in the brain. In fact, the demarcation between acute COVID-19 and Long COVID is becoming blurred. The UK Biobank has conducted a magnetic resonance study on people aged between 51 to 81 years old, which revealed some concerning findings. Specifically, the study highlighted a significant reduction in the thickness of gray matter in the brain, as well as tissue contrast in two specific regions – the orbitofrontal cortex and parahippocampal gyrus. (65) They also saw a reduction in global brain size in those having COVID-19 relative to controls. Post COVID-19 patients also reported a greater cognitive decline approximately 6 months after infection. A follow-up study indicates that although some patients seem to recover cognitively, patients with symptoms can have cognitive issues after 2 years, suggesting an average 10-year increase in aging of the brain. (66)

    The physical changes in the brain caused by SARS-COV-2 may take months or years to become apparent. Evidence suggests that recovery can take years and may not be complete. There is solid evidence that at least in severe infections the same chemical structures found in the brains of neurodegenerative patients occur (e.g., Parkinson’s disease, Alzheimer’s disease). (67) A worrisome study has shown that Alzheimer’s disease and COVID-19 patients, adjusted for age and gender, show similar molecular and cellular changes. (68) It has been suggested that COVID-19 might well lead to a higher predisposition of Alzheimer’s disease or dementia, (69) and those with already existing dementia are more likely to see a more rapid progression following SARS-COV-2 infection. (70) Similar circumstances have been observed for Parkinson’s disease. A very real possibility exists that we will see a major increase in neurodegenerative diseases in increasingly younger cohorts in the following decades after the pandemic. And, Long COVID incidence has not changed with omicron, (71,72) indicating that the damage continues with new variants and reinfections.

    The Endothelium and Blood Vessels

    Almost every pathological process during a COVID-19 infection and many in Long COVID can be related to its effects on the endothelial cells in the vasculature. Endothelial cells form the barrier between blood or lymphatic solution and the vessel walls controlling the flow of substances and fluid into and out of a tissue. These cells are critical to all functions involving circulation. SARS-COV-2 infection leads to elevated turnover of endothelial cells. (73) Data suggest that even for those who have had COVID-19 without symptoms, there is damage to the endothelial tissues. (74-77)

    The endothelium is a thin layer of cells that lines the inside of blood vessels, and it plays a significant role in maintaining vascular health. In COVID-19 patients, the virus can invade and damage these endothelial cells. This damage can lead to the rarefaction of vascular capillaries to become so minuscule that only a single red blood cell can pass through at a time. Unfortunately, this can also lead to the formation of microthrombi—small blood clots that block or restrict blood flow in the capillaries. In severe COVID-19, these microthrombi can form on a large scale which can lead to stroke or organ failure. In a 2021 review of 151 autopsies of those dying of COVID-19 were considered, microthrombi in the lung were found in 73% (91 patients), 11 % in the heart, 24% in the kidney, and 16 % in the liver. (76) Hence, the observation of damage to endothelial cells in asymptomatic COVID-19 patients (73) bodes poorly for the long-term impact of organ damage. This damage is likely to go unnoticed at first but may be significant in the aging of organs and is likely to be increased with repeated infections.

    The Endocrine System

    The endocrine system is responsible for regulating hormones that control numerous bodily functions, such as metabolism, immune response, stress response, and more. The endocrine system is complex, comprising hormone-producing cells and organs that serve to maintain homeostasis and to modulate the immune response to infections. Several studies have reported multiple endocrine and metabolic abnormalities following virus infections, such as human immunodeficiency virus type-1 (HIV-1), (78) coxsackieviruses B, (79) and now SARS-CoV-2. (80) Although many viral infections have been known to affect the endocrine system, (81) the large number of infections and reinfections with SARS-COV-2 makes understanding the impact of this infection on these effects important. COVID-19 can impact the endocrine system in several ways. For example, SARS-COV-2 infection increases the possibility of incident diabetes and antihyperglycemic use. (82) Endocrine diseases include adrenal insufficiency, type 1 and 2 diabetes, Cushing’s syndrome, and thyroid disease. (83) The long list of effects of COVID-19 on the endocrine system includes the following (80,84)

    1) Direct viral effects on endocrine tissues: ACE2 receptors, which the virus uses to enter human cells, are found in various endocrine organs like the pancreas, thyroid, and adrenal glands. Infection of these tissues can potentially disrupt hormone production and regulation. One such outcome is Graves disease, (84) an autoimmune disorder where the immune system mistakenly attacks the thyroid gland. Reports suggest that SARS-CoV-2 may cause thyroid inflammation in some individuals. (85) This condition, known as De Quervain’s thyroiditis, can lead to temporary thyroid dysfunction as well as thyroid tissue damage, which may affect individuals with or without preexisting autoimmune thyroid conditions like Graves’ disease or Hashimoto thyroiditis. More generally, COVID-19 has been associated with thyroid dysfunction, including both hyperthyroidism and hypothyroidism, (86-88) which can have important health implications. 

    2) Hyperinflammation including cytokine storms: During the acute phase of infection COVID-19 can lead to an excessive immune response and hyperinflammation both short or long-term, which can negatively impact the function of several endocrine organs, such as the pituitary gland, (89) leading to long term hormone imbalances. 

    3) Long-term metabolic changes: These can include glucose intolerance or a compromised response to insulin in the body, potentially leading to the development of type 2 diabetes in adults, and in some cases insulin resistance leading to type 1 diabetes in children. (82) The virus may also affect the function of the pancreas, (90) where insulin is produced. 

    4) Reproductive hormone changes: The impact of SARS on reproductive health is significant with reports indicating that the virus can temporarily disrupt menstrual cycles in women (91) and impact fertility in both women and men. (92) But It can also lead to an increased risk of hypogonadism and erectile dysfunction, (93,94) negatively affecting sperm quality parameters, (95) and crossing the placental barrier to infect and damage the placenta and fetus potentially several months following birth. (96-98) This can result in stillbirths, preeclampsia, fetal loss, and preterm birth. (99)

    It is important to note that our understanding of how COVID-19 affects the endocrine system across the population is continuing to develop. However, the existence of significant impacts is already apparent. 

    The Immune System

    The immunology of COVID-19 and Long COVID have recently been reviewed. (13,21) Immune dysregulation is generally considered to be a manifestation of Long COVID, and it occurs in patients after the full spectrum of illness from mild to severe COVID-19. However, Long COVID is usually defined by symptoms, whereas immune dysregulation doesn’t have distinctive symptoms on its own. However, it becomes apparent through recurrent infections. COVID-19 can dysregulate all the common aspects of the immune system. The duration of this dysregulation is still being investigated. The effects of COVID-19 are seen in T cells, (100) B cells, (101) dendritic cells, (102) monocytes, (103) and platelets, (104) among others. This results in increased vulnerability to other infections, (105) for example a more than fourfold increase in risk for other viral infections. (12)

    COVID-19 causes increased cellular turnover leading to aging of immune cells. These cells have limitations in their proliferative capacity and have a limited ability to divide and create new cells before cell division stops. SARS-COV-2 has been found to have detrimental effects on the length of cells’ telomeres, which are essential for cell proliferation. With each cell division, these telomeres are effectively shortened, potentially leading to accelerated aging and a higher risk of developing various diseases. T cell production is dependent on telomere length and these shorten naturally with age. Thus, the elderly have shorter telomeres. After SARS-COV-2 infection, these telomeres are also shorter. (106,107) This could explain why older adults appear to be more susceptible to reinfection following a SARS-COV-2 infection. (108) 

    Viral persistence can lead to a variety of damaging effects on the immune system. A new preprint provides good evidence that even people who are asymptomatic after SARS-COV-2 infection have signs of immune activation that localize in areas of the body from which one can identify the virus up to two years after infection. (109) These include the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. These data suggest that Long COVID and acute COVID-19 are not different entities, but the same infection at different levels of severity and longevity. (110)

    Implications of these findings are that several forms of damage lead to a condition similar to accelerated aging, with telomeres, mitochondria, the nervous, vascular, endocrine and immune system all showing decreased capacity and resilience. Increases in heart and neuro-inflammation can be caused by these long-lasting immune effects. In essence, this is accelerated aging of the tissues. Instead of being predominantly found in the elderly, in the near future T-cell controlled illnesses might move to middle age, even more so for immunocompromised individuals, dramatically reducing lifespan.

    Other Organs and Systems

    Lungs: COVID-19 often begins with respiratory symptoms, and severe cases can lead to acute respiratory distress syndrome. An impact on pulmonary function continues for one fourth of COVID-19 patients, who have impairment of pulmonary function a year after illness. (33) Fibrosis and scarring of lung tissue can lead to chronic respiratory impairment, including but much more widespread than recognized Long COVID respiratory symptoms. 

    Kidneys: Kidney damage and acute kidney injury have been observed in Long COVID patients. (111) Prolonged kidney dysfunction can lead to chronic kidney disease, which may require ongoing medical management or dialysis, and can have severe consequences if it cannot be controlled effectively.

    Intestines: SARS-CoV-2 can infect cells in the intestines, and some COVID-19 patients experience gastrointestinal symptoms. (112) There is ongoing research into potential long-term gastrointestinal complications and impacts on the gut microbiome. (113)

    Blood: The SARS-COV-2 virus has been associated with protein changes and long-standing blood changes including microclots in many patients. (114-116) 

    COVID-19 and SARS-COV-2 adversely affects nearly every organ in the body including also the skin, (117) the eyes, (118) the ears, (119) etc. 


    The importance of Long COVID symptoms impacting many millions around the world is gaining recognition. (120) While symptomatic Long COVID affects 10-30% of those infected, and its widespread impact is great enough to affect macroeconomic conditions, (121) it is only part of the long-term consequences of SARS-COV-2 infections. Varied levels of organ damage from COVID-19 have been shown to occur in over 50% of those infected. Organ damage leads to reduced functional capacity and physiological reserve of organs that is consistent with reduced health, reduced life expectancy, and increased vulnerability to future infections and conditions. It is also manifest in acute events such as heart attacks, strokes, as well as recurrent infections of other kinds. Organ damage is an important substrate for Long COVID symptoms, and the symptoms of Long COVID may be considered the tip of the iceberg of multisystem and organ damage manifestations. What is important to recognize is that even the known severe consequences of Long COVID are only part of the long-term consequences of COVID-19. It is crucial to acknowledge that SARS-CoV-2 poses significant threats that are further exacerbated by reinfections, resulting in a detrimental impact on various aspects of health. As we continue to study these impacts to better address them we must take preventive measures to avoid repeated infections. (122)


    We thank Nicholas Bertram for reading and commenting on the language in this manuscript. 



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    63. Han Y, Yang L, Kim TW, et al. SARS-CoV-2 Infection Causes Dopaminergic Neuron Senescence. Res Sq [Preprint]. 2021 May doi: 10.21203/ Update in: Cell Stem Cell. 2024 Jan 10;: PMID: 34031650; PMCID: PMC8142658.

    64. Zhu H, Byrnes C, Lee YT, et al. SARS-CoV-2 ORF3a expression in brain disrupts the autophagy–lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis. The FASEB Journal 37: e22919 (2023).

    65. Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604, 697–707 (2022).

    66. Guo P, Benito Ballesteros A, Yeung SP, et al. COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study. Front. Aging Neurosci. 14:804937 (2022).

    67. Szabo MP, Iba M, Nath A, et al. Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS. Exp Mol Med. 54: 447–454 (2022).

    68. Cheetham NJ, Penfold R, Guinchiglia V, The effects of COVID-19 on cognitive performance in a community-based cohort: a COVID symptom study biobank prospective cohort study. eClinicalMedicine 62: 102086 (2023).

    69. Al-Aly Z, Rosen CJ, Long Covid and Impaired Cognition — More Evidence and More Work to Do. N Engl J Med. 390: 858-860 (2024).

    70. Dubey S, Das S, Ghosh R, Dubey MJ, Chakraborty AP, Roy D, Das G, Dutta A, Santra A, Sengupta S, Benito-León J. The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia. J Alzheimers Dis Rep. 7:119-128 (2023).

    71. Griggs E, Trageser K, Naughton S, Recapitulation of pathophysiological features of AD in SARS-CoV-2-infected subjects. eLife 12: e86333 (2023).

    72. Magnusson K, Kristoffersen DT, Dell’Isola A, et al. Post-covid medical complaints following infection with SARS-CoV-2 Omicron vs Delta variants. Nat Commun. 13: 7363 (2022).

    73. Ben-Ami R, Loyfer N, Cohen E, Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients. Preprint. bioRxiv 2023.07.28.550957 (2023).

    74. Pretorius E, Venter C, Laubscher GJ, et al. Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma: a preliminary report. Cardiovasc Diabetol.19: 193 (2020).

    75. Mroueh A, Fakih ,. Carmona A, et al. COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway. J. Thrombosis and Haemostasis 22: 286-299 (2024).

    76. Parra-Medina R, Herrera S, Mejia J, Systematic Review of Microthrombi in COVID-19 Autopsies. Acta Haematol. 144: 476–483 (2021).

    77. Turner S, Khan MA, Putrino D,et al. Long COVID: pathophysiological factors and abnormalities of coagulation. Trends Endocrinol Metab. 34: 321–44 (2023).

    The Endocrine System

    78. Zaid D, Greenman Y, Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinology and Metabolism. 34: 95-105 (2019).

    79. Nekoua MP, Alidjinou EK, Hober D, Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol. 18: 503–516 (2022).

    80. Clarke SA, Abbara A, Dhillo WS, Impact of COVID-19 on the Endocrine System: A Mini-review, Endocrinology 163: bqab203 (2022).

    81. Nekoua MP, Debuysschere C, Vergez I, et al. Viruses and Endocrine Diseases. Microorganisms 11: 361 (2023).

    82. Xie Y, Al-Aly Z, Risks and burdens of incident diabetes in long COVID: a cohort study. The Lancet Diabetes & Endocrinology 10: 311-321 (2022).

    83. Murugan AK, Alzahrani AS, SARS-CoV-2 plays a pivotal role in inducing hyperthyroidism of Graves’ disease. Endocrine 73: 243–254 (2021).

    84. Steenblock C, Toepfner N, Beuschlein F, et al. SARS-CoV-2 infection and its effects on the endocrine system. Best Practice & Research Clinical Endocrinology & Metabolism 37: 101761 (2023).

    85. Çabuk SA, Cevher AZ, Küçükardalı Y, Thyroid Function During and After COVID-19 Infection: A Review. TouchREVIEWS in Endocrinology 18: 58–62 (2022).

    86. Rossetti CL, Cazarin J, Hecht F, et al. COVID-19 and thyroid function: What do we know so far? Front. Endocrinol. 13: 1041676 (2022).

    87. Lauri C, Campagna G, Glaudemans AWJM, et al. SARS-CoV-2 Affects Thyroid and Adrenal Glands: An 18F-FDG PET/CT Study. Biomedicines 11: 2899 (2023).

    88. Lui DTW, Lee CH, Woo YC et al. Thyroid dysfunction in COVID-19. Nat Rev Endocrinol (2024).

    89. Silva MJA, Ribeiro LR, Gouveia MIM, et al. Hyperinflammatory Response in COVID-19: A Systematic Review. Viruses 15: 553 (2023).

    90. Abramczyk U, Nowaczyński M, Słomczyński A, et al. Consequences of COVID-19 for the Pancreas. Int. J. Mol. Sci. 23: 864 (2022).

    91. Carp-Veliscu A, Mehedintu C, Frincu F, et al. The Effects of SARS-CoV-2 Infection on Female Fertility: A Review of the Literature. Int. J. Environ. Res. Public Health 19: 984 (2022).

    92. Depuydt C, Bosmans E, Jonckheere J, et al. SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients. eBiomedicine 93: 104640 (2023).

    93. YamaYamamoto Y, Otsuka Y, Sunada N, et al. Detection of Male Hypogonadism in Patients with Post COVID-19 Condition. Journal of Clinical Medicine. 11: 1955 (2022).

    94. Kaynar M, Gomes ALQ, Sokolakis I, et al. Tip of the iceberg: erectile dysfunction and COVID-19. Int J Impot Res. 34: 152–157 (2022).

    95. Aksak T, Satar DA, Bağci R, et al. Investigation of the effect of COVID-19 on sperm count, motility, and morphology. J Med Virol. 94: 5201-5205 (2022).

    96. Joshi B, Chandi A, Srinivasan R, et al. The placental pathology in Coronavirus disease 2019 infected mothers and its impact on pregnancy outcome. Placenta 127: 1–7 (2022).

    97. Jin JC, Ananthanarayanan A, Brown JA, et al. SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy. Pediatr. Res. 93: 1375–1382 (2023).

    98. Stoecklein S, Koliogiannis V, Prester T. et al. Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI. The Lancet Respiratory Medicine 10: e36–e37 (2022).

    99. Simon E, Gouyon J-B, Cottenet J, et al. Impact of SARS-CoV-2 infection on risk of prematurity, birthweight and obstetric complications: A multivariate analysis from a nationwide, population-based retrospective cohort study. BJOG An Int. J. Obstet. Gynaecol. 129: 1084–1094 (2022).

    The Immune System

    100. Diao B, Wang C, Tan Y, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front. Immunol. 11: 827 (2020).

    101. Jing Y, Luo L, Chen Y, et al. SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism. Sig Transduct Target Ther. 6: 345 (2021).

    102. Chang T, Yang J, Deng H, et al. Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection. Front. Immunol. 13: 843342 (2022).

    103.Ryan FJ, Hope C.M, Masavuli MG, et al. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection. BMC Med. 20: 26 (2022).

    104. Martins-Gonçalves R, Campos MM, Palhinha L, et al. Persisting Platelet Activation and Hyperactivity in COVID-19 Survivors.Circulation Research 131: 944–947 (2022).

    105. Wang L, Davis PB, Berger N, et al. Association of COVID-19 with respiratory syncytial virus (RSV) infections in children aged 0–5 years in the USA in 2022: a multicentre retrospective cohort studyFamily Medicine and Community Health 11: e002456 (2023).

    106. Cao X, Li W, Wang T, et al. Accelerated biological aging in COVID-19 patients. Nat Commun. 13: 2135 (2022).

    107. Mongelli A, Barbi V, Gottardi Zamperla M, et al. Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors. Int. J. Mol. Sci. 22: 6151 (2021).

    108. Aviv A, The bullwhip effect, T-cell telomeres, and SARS-CoV-2. The Lancet Healthy Longevity 3: E715-721 (2022).

    109. Peluso MJ, Ryder D, Flavell R, et al. Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19. Preprint.


    111. Bowe B, Xie Y, Xu E, Al-Aly Z, Kidney Outcomes in Long COVID. J. Amer. Soc. Nephrology 32: 2851-2862 (2021).

    112. Natarajan A, Zlitni S, Brooks EF, et al., Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection, Med, 3: 371-387 (2022).

    113. Bernard-Raichon L, Venzon M, Klein J, et al. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat Commun. 13: 5926 (2022).

    114. Wang C, Yu C, Jing H, et al. Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation. Front. Cell. Infect. Microbiol. 12: 861703 (2022).

    115. Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 479: 537–59 (2022).

    116. Grobbelaar LM, Venter C, Vlok M, et al. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19. Biosci Rep. 41: BSR20210611 (2021).

    Other Organs and Systems

    117. Martora F, Villani A, Fabbrocini G, Battista T. COVID-19 and cutaneous manifestations: A review of the published literature. J Cosmet Dermatol. 22: 4-10 (2023).

    118. Gedik B, Yuksel O, Kazim Erol M, et al. Evaluation of the retina, choroid and optic disc vascular structures in individuals with a history of COVID-19 Évaluation des structures vasculaires de la rétine, de la choroïde et du disque optique chez les personnes ayant des antécédents de COVID-19. Journal Français d’Ophtalmologie. 47: 104014 (2024).

    119. Dorobisz K, Pazdro-Zastawny K, Misiak P, et al. Sensorineural Hearing Loss in Patients with Long-COVID-19: Objective and Behavioral Audiometric Findings. Infect Drug Resist.16: 1931-1939 (2023).


    120. Addressing Long COVID: Advancing Research and Improving Patient Care.

    121. Cutler DM, The Economic Cost of Long COVID: An Update.

    122. Šalamon S, Ewing A, Fox G, et al. SARS-CoV-2 and COVID-19: From Crisis to Solution, WHN Science Communications 5: 1-1 (2024).

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