Long-term Effects of COVID-19
    (Long Covid)

    Welcome to our Long Covid resource centre. As with our COVID-19 communications, we have compiled ongoing evidence-based research and information regarding the condition.

    If you are aware of helpful research or literature in this field we would be very grateful for your input at longcovid@otandp.com.

     

    About Long Covid

    As we continue to learn more about COVID-19, we are just beginning to understand the long-term effects of the infection.

    Long Covid is a multisystem, inflammatory condition where COVID-19 symptoms continue to linger months beyond the initial illness, or new systems develop weeks or months after the acute infection has subsided[1].

    Symptoms may include debilitating fatigue, brain fog, shortness of breath, heart palpitations, and exercise intolerance, among many others[2]. The World Health Organisation estimates that there have been more than 200 symptoms reported in patients[3].

    Although the understanding of Long Covid is still in its infancy, the research suggests that the condition is widespread[4]. The UK Office of National Statistics (ONS) found that 13.7% of Covid positive people reported at least one symptom after twelve weeks based on a cohort of 20’000[5].

    A small study of 30 discharged patients in Hong Kong led by City University suggested that 80% of patients had at least one persistent symptom at six months after infection and one-third of patients had more than three symptoms at six months[4].

     

    Long Covid Classifications

    According to the National Institute for Health and Care Excellence (NICE), to effectively diagnose, treat and manage a condition, it needs to be defined and distinguished from other conditions[6].

    The following classification system has been developed in the UK, with a similar model put in place by the NIH in the US:

    • 4 Weeks
    • 4-12 Weeks
    • 12+ Weeks
    • Long Covid

    Acute COVID-19

    Symptoms of COVID‑19 for up to 4 weeks.

    Ongoing COVID-19

    Symptoms of COVID‑19 from 4 weeks up to 12 weeks.

    Post Covid / Post Acute Covid Syndrome (US)

    Symptoms of COVID-19 last 12+ weeks while the possibility of an alternative underlying disease is also being assessed.

    Long Covid

    Symptoms that continue or develop after acute, ongoing and post COVID-19, and can’t be explained by an alternative diagnosis.

    Who is More Likely to Get Long Covid?

    Unlike acute infection survival rates, Long Covid affects people of all ages, including children and young people[7].

    Research so far suggests that Long Covid disproportionately affects women, consistent with autoimmune conditions like chronic Lyme disease [8].

     

    Current Long Covid Theories

    Post-viral illnesses aren’t a new phenomenon, there have been links between viral infection and some form of post-viral fatigue, for example, SARS in 2003. In Hong Kong, a study amongst SARS survivors found that over 40% of respondents reported a chronic fatigue problem 40 months after infection[9]. Similarly, in the Middle-Eastern Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, prolonged symptoms and fatigue were reported up to 18 months after acute infection[10].

    There are broadly three different theories, which are not mutually exclusive, for the prevalence of Long Covid:

    1. The persistence of Sars-Cov-2 viral infection or viral debris
    2. Autoimmune reactions to the primary viral trigger
    3. Ongoing inflammatory reaction

    Unfortunately, the lack of a single specific test makes the diagnosis of Long Covid challenging. Current treatment globally is based on managing the specific symptoms individual patients are experiencing.

     

    patient getting information on Long Covid

     

    Post-acute COVID-19 Sequelae and Diagnostic Tools

    Cognitive Function / Neurological Symptoms

    Reported Cognitive and Neurological Symptoms:

    • Headaches
    • Exhaustion
    • Brain fog
    • “Alzheimers-like” memory problems
    • Persistent impairment in sustained attention
    • Loss of smell
    • Tingling sensations
    • Inability to speak
    • Strokes
    • Seizures
    • Changes in mood
    • Sleep disturbance

    There is increasing evidence to suggest that in the long term, a COVID-19 infection may cause some level of brain damage and cognitive impairment.

    One British study points to brain damage directly by encephalitis (brain inflammation)[11]. Other research data also suggests Covid infection is a risk factor for strokes and dementia, affecting even younger patients[12]. Covid infections have also been linked to brain damage through a lack of oxygen.

    Diagnostic Tests for COVID-19 Neurological Complications:

    As there is no specific test for Long Covid, diagnosing the condition revolves around ruling out the possibility of alternative diseases. When patients present with neurological symptoms, the following battery of tests can be run:


    • Blood sample to look at the prevalence of antibodies
    • CAT scan
    • MRI
    • fMRI
    • S100b blood test (more typically used to ascertain the extent of concussion damage in concussion patients)

    Current Research on Neurological Long Covid Symptoms:

    • (July 2020) Involvement of the central nervous system. Italian researchers detected viral particles in the endothelial cells lining the blood vessels of the brain in a post-mortem examination[13].
    Cardiovascular Symptoms
    Reported Cardiovascular Symptoms:
    • Heart beating rapidly
    • Heart palpitations
    • Chest tightness or pain
    • Chest discomfort
    • Feeling lightheaded or dizzy
    • Shortness of breath
    • Myocardial hypertrophy
    • Coronary artery atherosclerosis
    • Focal myocardial fibrosis
    • Acute myocardial infarction
    • Cardiac hypertrophy

    One of the most commonly reported symptoms after a COVID-19 infection is heart palpitations and tightness of the chest, illustrating that the virus can affect the heart.

    A study published in the British Medical Journal cited that cardiopulmonary symptoms, especially difficulty breathing (dyspnoea) were the most commonly reported. 35.7% felt symptoms 3-months post covid, and 22.1% continue to feel symptoms 6-months post covid[14]

    Diagnostic Tests for COVID-19 Cardiovascular Conditions:

    As there is no specific test for Long Covid, diagnosing the condition revolves around ruling out the possibility of alternative diseases. The following tests can be run to understand cardiovascular health:

    • Cardiac scan/Cardiac MRI
    • Measuring levels of circulating endothelial cells (CECs)
    • Endothelial activation markers
    • Electrocardiogram
    • Echocardiogram
    Gastrointestinal Symptoms
    Reported Gastrointestinal Symptoms:
    • Loss of appetite
    • Nausea
    • Acid reflux
    • Diarrhoea
    • Vomiting
    • Abdominal pain
    • Bloody stools

    A Lancet study on Gastrointestinal sequelae post-covid infection found that loss of appetite, nausea, acid reflux and diarrhoea are common in patients 3 months discharge from hospitalisation due to COVID-19[15].

    There are also a few studies linking gastrointestinal symptoms in children. One Spanish study found that ​​70% of children around 80.5 months old had reported abdominal pain linked to COVID-19 and multisystem inflammatory syndrome (MIS-C)[16]. Another study also similarly cites that MIS-C in children with COVID-19 most commonly reported fevers and gastrointestinal symptoms[17].

    Diagnostic Tests for GI Conditions:

    The following tests can be run to understand the GI symptoms:

    • MRI
    • CT scan
    • Faecal occult blood test
    • Stool culture
    • Ultrasound
    • Colonoscopy
    • Esophageal manometry

    Current Research on GI Symptoms:
    • (July 2021) Gastrointestinal and liver diseases associated with COVID-19. Researchers went through 590 articles to find that GI manifestations are common in COVID-19 patients[18].
    Psychological Symptoms
    Reported Psychological Symptoms:
    • Chronic fatigue
    • Anxiety
    • Depression
    • Headaches
    • Sleep disorders
    • Memory loss
    • Impaired quality of life
    • Phobias
    • Avoidance behaviours
    • Loss of concentration
    • PTSD

    While most research focuses on the short-term effects of COVID-19 on mental health, there is evidence to suggest that long-term mental health effects are anticipated to be intensified. One paper even suggests that failure to address the mental health issues stemming from the pandemic is likely to prolong its impact.

    The psychological impact of diseases is not a new phenomenon. Both SARS and MERS were also found to be associated with psychiatric and neuropsychiatric symptoms, the most common ones included confusion, depressed mood, anxiety, panic attacks, psychotic symptoms and delirium [19]. During the post-illness stage, depression, anxiety, irritability, memory impairment, fatigue, insomnia and post-traumatic stress disorder were frequently reported [19], much like we are seeing with many post-covid patients.

    Diagnostic Tests for Psychological Conditions:

    The following tests can be run to understand the psychological impact:

    • Brain imaging
    • Anxiety screening
    • Depression screening
    • PTSD screening
    Respiratory Symptoms
    Reported Respiratory Symptoms:
    • Shortness of breath or difficulty breathing
    • Persistent cough
    • Chest tightness
    • Chest pain
    • Decreased exercise tolerance, having to stop to “catch” your breath
    • Tiredness or fatigue
    • Decreased peak exercise performance in elite athletes

    The obvious place to check for long-term damage is in the lungs because COVID-19 begins as a respiratory infection. Many studies have published consistent findings that lower lobes of the lungs are the most frequently damaged, and the majority of the abnormalities observed by computed tomography were ground-glass opacities. These indicate inflammation, that might make it difficult to breathe during sustained exercise.

    Diagnostic Tests for COVID-19 Respiratory Conditions:

    As there is no specific test for Long Covid, diagnosing the condition revolves around ruling out the possibility of alternative diseases. The following tests can be run to rule out other causes and evaluate the full impact on the respiratory system.

    • Pulse oximetry
    • Spirometry
    • Sputum sampling
    • Arterial blood gas
    • Blood test for thrombo-embolism
    • Pulmonary function test
    • Chest XR
    • CT Thorax
    • High-Resolution CT Thorax
    • Pulmonary angiogram
    • Cancer markers
    • Bronchoscopy

    Current Research on Respiratory Symptoms:

    Post-COVID-19 survivors discharge care is recognised as essential and of high priority in the research field. Management of the respiratory sequelae is still evolving. Pulse oximetry has been suggested as a useful tool in monitoring those survivors with persistent respiratory symptoms though still waiting for evidence. Serial pulmonary function tests and half-yearly high-resolution computed tomography of the chest have also been proposed.[20][21][22]

    Renal Symptoms
    Reported Renal Symptoms:
    • Decreased urine output
    • Blood in urine
    • Frothy urine (bubbles in urine)
    • Swelling in the ankles, legs and around the eyes
    • Tiredness
    • Shortness of Breath
    • Confusion
    • Nausea
    • Seizures

    While the full extent of the health implications in Long Covid cases is unknown, the incidence of Acute Kidney Injury, where kidneys suddenly stop working properly estimate from 2.1 up to 29%. Research on the exact mechanism is underway. The current proposal is that sepsis may lead to cytokine storm syndrome or that direct cellular injury may occur due to the virus invasion leading to acute tubular necrosis or tubulointerstitial nephritis. Hospitalized patients, even those with mild symptoms are likely to experience lingering kidney damage, and end-stage kidney disease (ESKD). Clinical guidance of how to care for this group of people is currently a top priority.

    Diagnostic Tests for COVID-19 Renal Conditions:

    As there is no specific test for Long Covid, diagnosing the condition revolves around ruling out the possibility of alternative diseases. The following tests can be run to rule out other causes and evaluate the full impact on the renal system.

    • Renal function test for urea, creatinine and electrolytes including sodium, potassium, calcium, magnesium, phosphate, bicarbonate
    • Glomerular Filtration Rate
    • Blood for antibodies that may attack the kidneys
    • Hepatitis panel to rule out other causes of kidney injury
    • Urine Protein
    • Renal Ultrasound
    • CT Kidneys
    • MRI Kidneys
    • MR angiography of the kidneys

    Current Research on Renal Symptoms:

    Renal physicians are currently researching the long-term impacts that this pandemic will cause, bracing for a surge in the population of patients battling lasting illnesses and disabilities.

    • (Sept 2021) Kidney Outcomes in Long Covid. Journal of the American Society of Nephrology[23].

    Potential Treatments for Long Covid

    Long Covid is a growing problem worldwide. Here we look at some potential treatments based on the likely mechanisms of Long Covid such as inflammation and poor nutrition. This is not a treatment plan, please seek the advice of a healthcare practitioner before starting any treatment for Long Covid.

    Nutrition

    Please remember that most nutrients do not act like medicines. Supplements are effective if there is a deficiency but not once the deficiency is corrected.

    Iron Deficiency[25]

    A common cause of fatigue, particularly in women, and may be exacerbated by illness. Simple blood tests such as Ferritin levels will identify iron deficiency which can be corrected by intravenous infusion or replacement by mouth

    Vitamin D[27]

    A key vitamin for proper immunity and has anti-inflammatory action. The Vitamin is mostly generated by the action of sunlight on the skin so levels are likely to fall during lockdown and illness. Being fat-soluble, it can accumulate so ideally measure Vitamin D levels and supplement accordingly. However, supplementation with 2,000iu daily is safe for adults.

    Zinc Deficiency[27],[28]

    Common worldwide and a well-established cause of poor immunity. Generally, zinc comes with protein, so low protein diets are a risk, and the requirement for zinc also goes up with infection. Excessive long treatment with Zinc can cause copper deficiency although 30mg daily for 3-6 months will be safe.

    Selenium Deficiency[27]

    At OT&P we commonly see low Selenium levels in patients another nutrient that is necessary for immunity. Low Selenium is common for those who eat food from areas of low Selenium. Nuts and seeds contain Selenium only if they are grown in soil which contains selenium. The usual supplemental dose is 200mcg daily, and better absorbed as the Selenomethionine form.

    Omega 3 Fatty Acids[30]

    Present in fish oil and some plant-based oils are known to have anti-inflammatory effects. They reduce inflammatory messaging molecules and can even stabilize Mast Cells. Taking a good quality fish oil at 2 grams daily has been shown to reduce inflammation.

    Probiotics[31]

    We have written elsewhere about the ant-inflammatory effect of probiotics. Taking probiotics daily will improve immune function.

    Mast Cell Activation Syndrome

    Many patients with Long Covid have the symptoms of Mast Cell Activation Syndrome[35]. For more information, we have an article here. Like POTS, MCAS is a well-known phenomenon which is not limited to Long Covid. The treatments are targeted towards excessive histamine, so antihistamines which block the effect and medications that stop the histamine release.

    Postural Orthostatic Tachycardia (POTS)

    Many patients with Long Covid and Chronic Fatigue exhibit the signs and symptoms of POTS. That is on sitting up or standing from prone their heart rate increases and blood pressure may drop due to a disordered autonomic nervous system, that is the functions that are not regulated on a conscious level. POTS is reasonably common, it is estimated that, in the USA, there are more than a million patients with POTS, so there is experience in treating this condition.

    Natural Anti-Inflammatories

    Quercetin

    This is a natural flavonoid which decreases histamine release from Mast Cells and works in a similar way to Mast Cell stabilizing drugs such as Cromolyn. It is often formulated with Vitamin C and Bromelain to increase absorption.

    Curcumin

    This is a naturally occurring anti-inflammatory compound that has been used extensively as a naturopathic agent. Formulations are available with enhanced absorption. The main benefit for Curcumin over medical anti-inflammatories is the lack of gut side effects such as stomach ulcers.

    Psychotropic Medications

    Fluvoxamine

    An antidepressant has been proposed as a treatment for Covid[33]. Patients with chronic illness of any type, particularly with neurological symptoms and fatigue are often given antidepressant medications as part of the management plan. The SSRI antidepressant Fluvoxamine also has anti-inflammatory effects due to it being an agonist for the sigma-1 receptor. Patients with persisting inflammation as a driver for their Long Covid can consider Fluvoxamine if an antidepressant is needed.

    Melatonin

    This is a well-known supplement for insomnia and jet lag and widely available. In humans it is produced by the pineal gland and mitochondria. As well as inducing sleep Melatonin has strong antioxidant and anti-inflammatory effects and can also stabilize Mast Cells[34]. The dosage usually used is 6-10mg daily. Melatonin is safe, a common side effect is increased dreaming.

    Corticosteroids

    One reason for decreased mortality from severe Covid illness is the use of Corticosteroids. In the initial hospital trial, Dexamethasone was used. In out-patients, it is more usual to Prednisolone. Steroids are powerful anti-inflammatories but they also suppress the normal immune response to infection. In addition, if they are given for long they can suppress the normal production of corticosteroids in the Adrenal Glands. Short courses of Prednisolone can be used to treat Long Covid when inflammation is present but this should always be under medical supervision.

    Re-Purposed Drugs

    Atorvastatin

    A Statin cholesterol lowering drug that is being used to treat Long Covid[35]. In addition to blocking the manufacture of Cholesterol in the liver Statins are also strongly anti-inflammatory. Statins are used extensively so the long term safety profile is good. Because Statins also block the production of CoQ10, which is necessary for energy production, the side effects of Statins are not dissimilar to Long Covid, that is fatigue, brain fog and muscle pains. CoQ10 can be taken as a supplement along with Atorvastatin.

    Low Dose Naltrexone

    Low Dose Naltrexone (LDN) has been proposed as a potential treatment for Covid and Long Covid. Naltrexone is an opiate antagonist, that is it blocks the effect of opiates such as heroin, morphine and fentanyl. Naltrexone is used in situations of opiate overdose, a common cause of death in countries with opiate abuse problems

    The natural stimulators of opiate receptors are endorphins, which act as pain killers and anti-inflammatories. LDN, by blocking the opiate receptor for a short period of time, stimulates the body to make more endorphins and therefore increases their activity.

    The usual dose of a Naltrexone Tablet is 50mg, whereas in LDN doses ranging from 1mg to 4.5mg are commonly used. The effect of these low doses of naltrexone is to actually increase the natural endorphins stimulating the same opiate receptors that the drugs act on. These small increases in endorphins act as an anti-inflammatory and analgaesic.

    Long Covid Knowledge Centre

    Below we include the academic references to papers discussed in this document, in addition to external resources and support groups.

    General Long Covid Research and Summary Papers

    1. Centers for Disease Control and Prevention. (2021). ‘Post-COVID Conditions.’ CDC. 12 July 2021. Available at: <https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html> [Accessed 10 September 2021].

    2. National Health Service. (2021). ‘Long-term effects of coronavirus (long COVID)’ NHS. 2 September 2021. Available at: <https://www.nhs.uk/conditions/coronavirus-covid-19/long-term-effects-of-coronavirus-long-covid/> [Accessed 10 September 2021].

    3. The World Health Organization. (2021). ‘Episode #47 - Post COVID-19 condition.’ WHO. 30 July 2021. Available at: <https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science-in-5/episode-47---post-covid-19-condition> [Accessed 10 September 2021].

    6. National Institute for Health and Care Excellence. (2020). ‘COVID-19 rapid guideline: managing the long-term effects of COVID-19’. NICE. 18 December 2020. Available at: <https://www.nice.org.uk/guidance/ng188/chapter/Context> [Accessed 10 September 2021].

    8. Kent J. Nielsen, Jesper Medom Vestergaard., et al. (2021). ‘Day by day symptoms following positive and negative PCR tests for SARS-CoV-2 in non-hospitalised health-care workers: a 90-day follow-up study’. International Journal of Infectious Diseases. March 03, 2021. Available at: <https://www.medrxiv.org/node/310296.external-links.html> [Accessed 10 September 2021].

    20. Huang, Chaolin et al. (2021). ‘6-month consequences of COVID-19 in patients discharged from hospital: a cohort study’. The Lancet, Volume 397, Issue 10270, 220 - 232. 8 January 2021. Available at: <https://doi.org/10.1016/S0140-6736(20)32656-8> [Accessed 10 September 2021].

    41. Groff, D., Sun, A., & Ssentongo, A. E. (2021). Short- and long-term rates of postacute sequelae of SARS-COV-2 infection. JAMA Network Open. October 13, 2021. Available at: <https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784918.> [Accessed November 22, 2021]

    Investigations for Long Covid

    4. CUHK Faculty of Medicine. (2021). ‘CU Medicine Finds New Evidence for Link between Gut Microbiome and COVID-19 Severity Microbiome Imbalance Might Influence “Long COVID” Risk’. CUHK. 18 January 2021. Available at: <https://www.med.cuhk.edu.hk/press-releases/cu-medicine-finds-new-evidence-for-link-between-gut-microbiome-and-covid-19-severity-microbiome-imbalance-might-influence-long-covid-risk> [Accessed 10 September 2021].

    Clinical Manifestations of Long Covid

    5. Office for National Statistics. (2021). ‘Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 1 April 2021’. ONS. 1 April 2021. Available at: <https://www.ons.gov.uk/> [Accessed 10 September 2021].

    9. Lam MH, Wing Y, Yu MW, et al. (2009). ‘Mental Morbidities and Chronic Fatigue in Severe Acute Respiratory Syndrome Survivors: Long-term Follow-up’. Arch Intern Med. 2009;169(22):2142–2147. 14 December 2009. Available at: <doi:10.1001/archinternmed.2009.384> [Accessed 10 September 2021].

    10. Lee SH, Shin HS, Park HY, et al. (2019). ‘Depression as a Mediator of Chronic Fatigue and Post-Traumatic Stress Symptoms in Middle East Respiratory Syndrome Survivors'. Psychiatry Investig. 2019;16(1):59-64. 7 January 2019. Available at: <doi:10.30773/pi.2018.10.22.3> [Accessed 10 September 2021].

    11. Paterson RW, Brown RL, Benjamin L, et al. (2020). ‘The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings’. Brain. 2020;143(10):3104-3120. 1 October 2020. Available at: <doi:10.1093/brain/awaa240> [Accessed 10 September 2021].

    12. Fridman S, Bres Bullrich M, Jimenez-Ruiz A, et al. (2020). ‘Stroke risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases. Neurology’. 2020;95(24):e3373-e3385. 15 September 2020. Available at: <doi:10.1212/WNL.0000000000010851> [Accessed 10 September 2021].

    13. Paniz-Mondolfi A, Bryce C, Grimes Z, et al. (2020). ‘Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)’. J Med Virol. 2020;92(7):699-702. July 2020. Available at: <doi:10.1002/jmv.25915> [Accessed 10 September 2021].

    14. Shoucri SM, Purpura L, DeLaurentis C, et al. (2021). ‘Characterising the long-term clinical outcomes of 1190 hospitalised patients with COVID-19 in New York City: a retrospective case series’. BMJ Open 2021;11:e049488. 1 June 2021. Available at: <doi: 10.1136/bmjopen-2021-049488> [Accessed 10 September 2021].

    15. Weng, Jingrong et al. (2021). ‘Gastrointestinal sequelae 90 days after discharge for COVID-19’. The Lancet Gastroenterology & Hepatology, Volume 6, Issue 5, 344 - 346. 9 March 2021. Available at: <https://doi.org/10.1016/S2468-1253(21)00076-5> [Accessed 10 September 2021].

    18. Sweed, D., Abdelsameea, E., Khalifa, E.A. et al. (2021). ‘SARS-CoV-2-associated gastrointestinal and liver diseases: what is known and what is needed to explore’. Egypt Liver Journal 11, 64. 31 July 2021. Available at: <https://doi.org/10.1186/s43066-021-00123-6> [Accessed 10 September 2021].

    19. Klaus W. Lange. (2021). ‘Coronavirus disease 2019 (COVID-19) and global mental health’. Global Health Journal. 13 February 2021. Available at: <https://doi.org/10.1016/j.glohj.2021.02.004.> [Accessed 10 September 2021].

    21. Zhao YM, Shang YM, Song WB, et al. (2020). ‘Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery’. EClinicalMedicine. 2020;25:100463. 25 August 2020. Available at: <doi:10.1016/j.eclinm.2020.100463> [Accessed 10 September 2021].

    22. Shah AS, Wong AW, Hague CJ, et al. (2020). ‘A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations’. Thorax 2021;76:402-404. 3 December 2020. Available at: <https://thorax.bmj.com/content/76/4/402> [Accessed 10 September 2021].

    23. Benjamin Bowe, Yan Xie, Evan Xu, Ziyad Al-Aly. (2021). ‘Kidney Outcomes in Long COVID’. American Society of Nephrology. 1 September 2021. Available at: <https://doi.org/10.1681/ASN.2021060734> [Accessed 10 September 2021].

    Potential Treatments for Long Covid

    25. OT&P Healthcare. (2020, March 27). Is anaemia making me tired? OT&P – Internationally Accredited Medical Clinics in Hong Kong. Retrieved October 5, 2021, from https://www.otandp.com/blog/is-iron-deficiency-anaemia-causing-my-fatigue.

    26. Vimaleswaran, K. S., Forouhi, N. G., &amp; Khunti, K. (2021, March 4). Vitamin D and covid-19. The BMJ. Retrieved October 5, 2021, from https://www.bmj.com/content/372/bmj.n544.

    27. OT&P Healthcare. (2021, August 9). How nutrition and lifestyle can improve immunity against viral infections. OT&P – Internationally Accredited Medical Clinics in Hong Kong. Retrieved October 5, 2021, from https://www.otandp.com/blog/how-nutrition-and-lifestyle-can-improve-immunity-against-viral-infections.

    28. Kumssa, D. B., Joy, E. J. M., Ander, E. L., Watts, M. J., Young, S. D., Walker, S., &amp; Broadley, M. R. (2015, June 22). Dietary calcium and zinc deficiency risks are decreasing but remain prevalent. Nature News. Retrieved October 5, 2021, from https://www.nature.com/articles/srep10974.

    29. U.S. Department of Health and Human Services. (n.d.). Office of dietary supplements - selenium. NIH Office of Dietary Supplements. Retrieved October 5, 2021, from https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/.

    30. PC;, C. (n.d.). Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochemical Society transactions. Retrieved October 5, 2021, from https://pubmed.ncbi.nlm.nih.gov/28900017/.

    31. OT&P Healthcare. (2021, September 14). Gut Microbiota and Covid-19. OT&P – Internationally Accredited Medical Clinics in Hong Kong. Retrieved October 5, 2021, from https://www.otandp.com/blog/gut-microbiota-and-covid-19.

    32. Mast Cell Activation Syndrome (MCAS). American Academy of Allergy Asthma & Immunology. (n.d.). Retrieved October 5, 2021, from https://www.aaaai.org/conditions-treatments/related-conditions/mcas.

    33. Sukhatme, V. P., Reiersen, A. M., Vayttaden, S. J., &amp; Sukhatme, V. V. (1AD, January 1). Fluvoxamine: A review of its mechanism of action and its role in covid-19. Frontiers. Retrieved October 5, 2021, from https://www.frontiersin.org/articles/10.3389/fphar.2021.652688/full.

    34. Tarocco, A., Caroccia, N., Morciano, G., Wieckowski, M. R., Ancora, G., Garani, G., & Pinton, P. (2019, April 8). Melatonin as a master regulator of cell death and inflammation: Molecular mechanisms and clinical implications for newborn care. Nature News. Retrieved October 5, 2021, from https://www.nature.com/articles/s41419-019-1556-7.

    35. I-RECOVER Management Protocol for Long Haul COVID-19 Syndrome (LHCS) | Front Line COVID-19 Critical Care Alliance. (2021, August 11). Retrieved October 5, 2021, from https://covid19criticalcare.com/covid-19-protocols/i-recover-protocol/.

    36. Molderings, G. J., Brettner, S., Homann, J., &amp; Afrin, L. B. (2011, March 22). Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology &amp; Oncology. Retrieved October 5, 2021, from https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-4-10.

    37. Weiler CR; Austen KF; Akin C; Barkoff MS; Bernstein JA; Bonadonna P; Butterfield JH; Carter M; Fox CC; Maitland A; Pongdee T; Mustafa SS; Ravi A; Tobin MC; Vliagoftis H; Schwartz LB; (n.d.). AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management. The Journal of Allergy and Clinical Immunology. Retrieved October 5, 2021, from https://pubmed.ncbi.nlm.nih.gov/31476322/.

    38. Raj, S. R., Arnold, A. C., Barboi, A., Claydon, V. E., Limberg, J. K., Lucci, V.-E. M., Numan, M., Peltier, A., Snapper, H., Vernino, S., &amp; American Autonomic Society. (2021, June). Long-Covid Postural Tachycardia Syndrome: An American Autonomic Society Statement. Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society. Retrieved October 5, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976723/.

    39. Dani, M., Dirksen, A., Taraborrelli, P., Torocastro, M., Panagopoulos, D., Sutton, R., &amp; Lim, P. B. (2021, January). Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clinical medicine (London, England). Retrieved October 5, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850225/.

    40. GrubbMD, B. P., Grubb, B. P., Blair P. Grubb From the Cardiology Department of Medicine, &amp; Grubb, C. to B. P. (2005, June 7). Neurocardiogenic Syncope and Related Disorders of Orthostatic Intolerance. Circulation. Retrieved October 5, 2021, from https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.104.482018?url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org&amp;rfr_dat=cr_pub%2B%2B0pubmed&amp;.

    42. Alexander, S. (2021, November 17). Ivermectin: Much more than you wanted to know. Astral Codex Ten. Retrieved November 22, 2021, from https://astralcodexten.substack.com/p/ivermectin-much-more-than-you-wanted

     

    Long Covid in Children

    7. Buonsenso, D., Munblit, D., De Rose, C., Sinatti, D., Ricchiuto, A., Carfi, A. and Valentini, P. (2021). ‘Preliminary evidence on long COVID in children’. Acta Paediatrica, 110: 2208-2211. 09 April 2021. Available at: <https://onlinelibrary.wiley.com/doi/10.1111/apa.15870> [Accessed 10 September 2021].

    16. Öcal Demir et al. (2021). ‘SARS-CoV-2 associated multisystem inflammatory syndrome in children (MIS-C). A single center's experience’. Minerva Pediatrics. 23 April 2021. Available at: <https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1200473> [Accessed 10 September 2021].

    17. Rubens J H, Akindele N P, Tschudy M M, Sick-Samuels A C. (2021). ‘Acute covid-19 and multisystem inflammatory syndrome in children’. BMJ 2021; 372 :n385. 1 March 2021. Available at: <doi:10.1136/bmj.n385> [Accessed 10 September 2021].

    If you are aware of helpful research or literature in this field we would be very grateful for your suggestions at longcovid@otandp.com.

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