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Research

New research is constantly being released about Long COVID, as well as opportunities for people to take part in research to increase understanding of the condition. We will be updating this page regularly with the latest research and opportunities to take part in research.

We have information about a range of topics linked with Long COVID including:

Research opportunities – currently open

New Parliamentary Inquiry into Long COVID and Repeated COVID Infections

The House of Representatives health committee’s new parliamentary inquiry will examine the health, economic and educational impacts of Long COVID and repeated infections. The inquiry’s chair, Labor MP Mike Freelander, has stated that long COVID is emerging as a significant issue and that the current understanding is limited. Terms of reference:

  1. The patient experience in Australia of Long COVID and/or repeated COVID infections, particularly diagnosis and treatment;

  2. The experience of healthcare services providers supporting patients with Long COVID and/or repeated COVID infections;

  3. Research into the potential and known effects, causes, risk factors, prevalence, management and treatment of Long COVID and/or repeated COVID infections in Australia;

  4. The health, social, educational and economic impacts in Australia on individuals who develop Long COVID and/or have repeated COVID infections, their families, and the broader community, including for groups that face a greater risk of serious illness due to factors such as age, existing health conditions, disability and background;

  5. The impact of Long COVID and/or repeated COVID infections on Australia’s overall health system, particularly in relation to deferred treatment, reduced health screening, postponed elective surgery, and increased risk of various conditions including cardiovascular, neurological and immunological conditions in the general population; and

  6. Best practice responses regarding the prevention, diagnosis and treatment of Long COVID and/or repeated COVID infections, both in Australia and internationally.

  7. The inquiry is inviting submissions from those interested by November 18th 2023.

The ADAPT Study 

The St Vincent’s ADAPT study is recruiting volunteers who have tested positive for COVID-19 since January 2022. The ADAPT study is an ongoing observational cohort study focusing on symptomology post COVID-19 infection. Participation in this study would initially involve a screening visit to determine eligibility and to provide consent. Once eligible, participants would be required to attend 3–4 follow-up visits over a period of 1 year. Assessments will include symptom review, blood samples and health and wellbeing questionnaires. More information can be found here.

John Hopkins COVID Long Study  

The Johns Hopkins Bloomberg School of Public Health is conducting research on how the COVID-19 pandemic has impacted people’s lives, especially related to symptoms and recovery. If you would like to participate in this one-time, 20-minute survey please follow this link.  

Melbourne University Research

Melbourne University researchers are planning on conducting a prospective study of Long COVID with the use of T MRI brain scans as part of a collaborative research program. For more information please read here or email twi@unimelb.edu.au.

PERCEIVE (COVID heart) study  

The Baker Institute in Melbourne is conducting the Persistent cardiovascular effects of COVID-19 viral infection (PERCEIVE) study aimed at understanding whether COVID-19 causes damages to the heart and impacts functional capacity. To be eligible for this study, you must be aged over 45 years and have had a COVID-19 infection. For more information, please follow this link.  

Statin Treatment for COVID-19 to Optimise Neurological Recovery (STRONGER) 

STRONGER is an international clinical trial aimed at determining whether 40mg of a statin drug (statin drugs are typically prescribed to those with elevated cholesterol to improve cardiovascular health and reduce the risk of a heart attack or stroke), administered daily can improve neuro-cognitive function in adults with Long COVID neurological symptoms. The study is a collaboration between The George Institute for Global Health, UNSW Sydney, Monash University’s School of Public Health, University of Sydney and Sydney Local Health District. This trial is currently in its third phase and is predicted to complete in June 2023. For more information, please follow this link.   

Development of a 2-stage nutraceutical treatment protocol for adults with long-COVID-19 syndrome, exploring underlying pathophysiology and treatment effectiveness 

This study (trial ID: ACTRN12622001204730) is looking at the underlying pathophysiology of Long COVID followed by a staged treatment approach. Based on a trial status update on 02/12/23, this study is currently recruiting Long COVID patients in Australia. To be eligible, you must be over the age of 20, have had COVID-19 evident by PCR or RAT more than 3 months ago, persistent symptoms for longer than 3 months and have been referred to and assessed by trial doctor as suitable for the trial. The primary contact person for further information and recruitment is A/Prof Karin Ried at the National Institute of Integrative Medicine (phone +61 9912 9545 / karinried@nimm.com.au).  

The SA Long COVID study: A clinical registry defining the care needs for patients with Post-COVID-19 conditions in South Australia 

This study (trial ID: ACTRN12622000718741) is looking at how COVID-19 has affected people including their fitness, health and quality of life after their initial infection. Based on a trial status update on 14/03/23, this study is currently recruiting Long COVID patients in South Australia. To be eligible, you must be over the age of 18, have had COVID-19 evident by nucleic acid testing or rapid-antigen testing (RAT) and be at least 3 months from the onset of proven COVID-19 with symptoms that have persisted for 2 months with no other alternative diagnosis. Symptoms must be known or suspected to be associated with Long COVID. The primary contact person for further information and recruitment is Dr Angela Molga at the Department of Clinical Pharmacology (phone +61 08 70742701 / angela.molga@sa.gov.au).  

Signs and symptoms

Additional Long COVID symptoms to add to the ever-growing list

The symptoms associated with Long COVID seem to be increasing in number, reflecting both breadth and diversity in the presentation of this condition. A recent study has announced that hair loss, reduced libido, bowel incontinence and erectile dysfunction have been reported among Long COVID patients.

Long COVID reshapes the brain, science explains

Science has confirmed that COVID-19 triggers an inflammatory response and alters the nervous system for up to two years after initial infection. A UK based neuroimaging study has showed that even mild cases of COVID-19 can lead to a reduction in overall brain size, with specific effects seen in the frontal cortex and limbic system. These brain changes help to explain why Long COVID patients tend to suffer from mental health complaints and neurological deficits like depression and brain fog. Researchers are conducting vigorous testing to assess the cause of these brain changes. One hypothesis is that of a loss of integrity of the brain’s protective layer, the blood-brain-barrier, leading to the process of swelling and brain injury. Another hypothesis is related to infection of the cells that essentially ‘hold the brain together’. When these astroglia cells are damaged, their ability to support and nourish the brains neurons is reduced. 

Cardiovascular manifestations of Long COVID 

According to authors of a recently published review on Long COVID, “continued systemic and myocardial inflammation appears to be the main pathology for cardiac involvement in Long COVID”. Symptoms specific to the cardiovascular injury include palpitations, chest pain, breathlessness and postural dizziness with or without syncope (temporary loss of consciousness caused by fall in blood pressure). The authors state that further research is needed to devise a diagnostic tool “that can use a combination of clinical symptoms, biomarkers, ECG and imaging to define cardiac involvement in long COVID”.   

Long COVID and brain health

Among the long-term effects of COVID-19 infection, experts say that brain health is particularly at risk. Research has found that symptoms of Long COVID can mimic the symptoms that are displayed after a stroke. Further, there are a few single-case reports confirming cases of clinical Parkinsonism developing after a COVID-19 infection.

Long-term gastrointestinal outcomes of COVID-19 

A recent study published in the journal Nature Communications has shown that patients diagnosed with COVID-19 were more likely to experience gastrointestinal disorders a year after their initial infection compared to people who were not infected. The gastrointestinal disorders span across several disease categories which include motility disorders (abnormal muscle and nerve contractions that cause spasms or lack of motion along the gastrointestinal tract), acid related disorders (dyspepsia, gastroesophageal reflux disease – GERD, and peptic ulcer disease – PUD), functional intestinal disorders, acute pancreatitis, hepatic and biliary disease. The most common diagnoses were acid-related disorders such as GERB and PUD.  

Similar brain structure changes among Long COVID and ME/CFS patients  

Similar changes in brain structure have been identified among people who have Long COVID and encephalomyelitis/chronic fatigue syndrome (ME/CFS). The brain of 28 adults were compared by Griffith University scientists using a high-powered magnetic resonance imaging scanner (MRI). The findings show that the brainstem was significantly larger among the Long COVID patients and those with ME/CFE compared to those who had never been diagnosed with either condition. The researchers state that "the symptom overlap between ME/CFS and Long COVID patients is consistent with our current findings of similar abnormalities in the brainstem". Further people are currently being recruited to continue the investigation into the findings of this pilot study.  

Treatment options

Current clinical trials

Although treatment options are still limited, an article in the journal Nature has stated that 26 randomised controlled trials are currently underway, testing for potential therapies that may be helpful in Long COVID treatment. Based on the lack of clarity around the key causes and symptoms of the condition, researchers are trialling drugs that have been repurposed for other conditions. Many of the drugs that are being explored are those that target the inflammatory response and blood clotting. Interestingly however, cortisol replacement therapy and anti-depressant drugs are also being proposed as possible treatment options, specifically employed to target the cognitive-based symptoms such as brain fog and fatigue.

Long COVID could be diagnosed through the blood, a study reveals

A study that was recently been published in the Molecular Medicine Journal has shed light on the possible development of a blood test to aid the process of diagnosing Long COVID. The London based study found that Long COVID patients had 14 elevated biomarkers which the researchers have theorised is due to the blood vessels not only trying to heal themselves, but also reaching out to try to find healthy tissue. The researchers state that this new discovery could also lead to new treatments and medications for Long COVID patients.  

Anti-viral treatment may reduce risk of Long COVID 

A study has been conducted to examine the effects of the antiviral Paxlovid on the development of Long COVID. The participants within the study were patients who formed part of the US Veterans Health Administration system and who experienced a COVID-19 infection between March 1 and June 30, 2022. Based on the findings, the researchers state that treatment with Paxlovid during the acute phase of COVID-19 infection reduces the risk of post-acute adverse health outcomes. These outcomes were displayed regardless of vaccination status and whether the participants had been previously infected with COVID-19. Although promising, it is important to note that this study is yet to be peer reviewed and therefore, should not be used to guide clinical practice.  

L-arginine with vitamin C as a potential supplement for Long COVID patients 

An article has been published in the journal Nature that has examined the effects of L-arginine and vitamin C supplementation on the alleviation of Long COVID symptoms. Findings from the study showed that the l-arginine plus vitamin C supplementation improved walking performance, muscle strength, and endothelial function, reduced fatigue and restored serum l-arginine concentrations in adults with long COVID. The authors of the article state that "while no conclusive evidence exists on the beneficial effects of L-arginine supplementation on human performance, our findings indicate that a short course of L-arginine supplementation plus vitamin C supplementation may positively impact exercise capacity of adults with long COVID'' 

Living systematic review of therapeutic options for post-covid-19 condition 

A systemic review of potential therapeutic options for long COVID has been conducted by the Pan American Health Organisation (PAHO). The review includes all the identified clinical forms, symptoms and manifestations of long COVID for which an intervention has been assessed in a least one randomised controlled trial (RCT). For example, the review has identified 12 potential therapeutic options (including adaptogens, vitamins, enzymes and probiotics) to support fatigue dominant long COVID. To read the full review, click here. 

A possible treatment option for fatigue dominant long COVID   

The findings from a recent study demonstrated an association between a 4-week oral administration of a drug (metabolic modulator AXA1125) and significant improvements in documented physical and mental fatigue symptoms among patients with fatigue dominant long COVID. For more information about the study, please read here.  

Underlying causes

We need to understand the underlying causes

With the surge in COVID-19 cases and patients developing Long COVID, researchers are emphasising the need to understand the underlying causes. Better insight into the biology of Long COVID has emerged from recent studies that have examined the immune response and why it has gone “haywire”. Studies have shown that there are a handful of possible explanations. These include antibodies attacking the body’s own proteins, persistent antibodies being produced against the virus’s spike protein, low blood levels of the hormone cortisol and the re-activation of previous virus infections within the herpes virus family such as Epstein-Barr and Varicella-zoster.

Gastrointestinal symptoms post-acute COVID-19 syndrome – the role of the microbiome

Gastrointestinal symptoms are common among those suffering from Long COVID. A recent survey conducted on 1,783 COVID-19 survivors at six months elicited 749 responses, with 220 patients (29%) self-reporting symptoms of diarrhoea (10%), constipation (11%), abdominal pain (9%), nausea and/or vomiting (7%) and heartburn (16%). Although exact causal factors are still unknown, gut dysbiosis remains as an important part of ongoing research in this field.

Long COVID and Auto-immunity 

Autoimmunity refers to the condition where the immune system, rather than targeting foreign pathogens and infection, turns against its own body leading to a host of unwanted symptoms. Although the research remains unclear, scientists have long suspected that viral infections may be associated with chronic autoimmune diseases and there is evidence to suggest that the symptoms presented in Long COVID may in part, be the result of the activity of autoantibodies – antibodies that attack the immune system. Based on this emerging science, doctors are endeavouring to discover new therapies that control an overactive immune system. 

Poor mental health prior to COVID-19 infection increases risk of Long COVID

A study has found a link between poor mental health prior to contracting COVID-19 and an increased risk of developing Long COVID. The study was based on health data derived from nearly 55,000 US volunteers, most of whom were women. The analysis declared that high levels of psychological distress prior to infection with COVID-19, increased the risk of long-term illness by 32% to 46%.  

Long COVID linked to the common cold among patients with pre-existing rheumatic disease 

Based on a study conducted on patients with pre-existing rheumatic disease, researchers now believe that exposure to the common cold, another virus within the coronavirus family, may play a role in the development of Long COVID among some patients, particularly patients affected by arthritis. While this discovery does not necessarily translate to other categories of Long COVID, it may potentially serve as a diagnostic and treatment tool for patients with pre-existing arthritis.  

Prolonged stress prior to COVID-19 infection increases chances of Long COVID  

According to a Harvard University study released last month, psychological distress prior to COVID-19 infection increases the likelihood of developing Long COVID. Researchers claim that a possible explanation could be the relationship that prolonged mental distress has with the activation of inflammatory processes and the reprogramming of the immune cells which respond to new threats. 

Lost connections between nerve cells in the brain may explain cognitive symptoms 

More research is being conducted to determine what underlying determinants lead to the development of the commonly experienced cognitive symptoms among Long COVID patients. A recent study that looked at the effect of COVID-19 on brain organoids (miniature organs grown from stem cells) found that an excessive number of synapses (the connections between brain cells) were eliminated. This could explain why some people who are affected by Long COVID experience cognitive related symptoms such as brain fog.

The link between Long COVID and gastrointestinal health 

An imbalance of the bacteria within the gastrointestinal tract (medically known as 'dysbiosis') has been associated with poor health outcomes among COVID-19 patients who are supported with a ventilator during their hospital stay. These findings, among other research, has revealed that a disruption of the gut microbiome, otherwise known as the bacteria and other organisms such as fungi and viruses found within the gastrointestinal tract, and importantly a depletion of the bacteria that play a role in the immune system, during COVID-19 infection may provide an explanation behind the increased inflammation experienced by some individuals after infection.  

Long COVID and vitamin D deficiency  

A study that has been published in the Journal of Clinical Endocrinology & Metabolism (conducted in Italy) has found that low levels of vitamin D could increase the risk of developing long COVID. This study analysed the vitamin D levels of 100 patients aged between 51–71 who were admitted to hospital for COVID-19. At the six-month mark after their discharge from hospital, the researchers found lower vitamin D levels among the patients with long COVID. Read more here.  

Facts and statistics

Risk of Long COVID accumulates with repeated infection, states Professor Brendan Crabb

Burnet Institute Director and CEO, Professor Brendan Crabb AC, has warned that based on recent evidence, the risk of developing Long COVID is increased each time you are infected with the virus. Professor Crabb has told the ABC that what’s happening with COVID in Australia is simply not sustainable and that it has been estimated that between 100,000 and 500,000 Australians will suffer from Long COVID symptoms. He urges that in addition to continuing to explore treatment options, mask wearing also remains an important public health response.

Long COVID susceptibility higher among women

Although research is still in its infancy regarding the susceptibility and risk factor profile of Long COVID, studies have found that women are more likely than men to develop the condition. A study that involved 1.3 million people suggested that women were 22% more likely than men to be diagnosed with Long COVID. This has been attributed to a difference in how men and women's immune systems respond to the virus.

Long COVID categories 

As more people are affected by Long COVID, it has become apparent that it can be divided into various categories.  

1. The first category of Long COVID includes the combination of organ damage, profound physical debilitation and poor mental health inflicted by severe pneumonia and resultant critical illness.  

2. The second category refers to the new onset of recognised medical conditions like heart disease, a stroke, or a blood clot – after a mild COVID-19 infection.  

3. A third category is that of respiratory symptoms that last longer than expected but that are not associated with lung damage, critical illness or a new diagnosis like a heart attack or diabetes.  

 

Beyond these differing presentations of the condition, for some people affected by Long COVID the condition presents as a chronic illness – a complex of numerous unexplained, potentially debilitating and varied symptoms all of which typically follow a mild acute respiratory infection.  

Adam Gaffney – a pulmonary and critical-care physician and an assistant professor at Harvard Medical School stated that, "testing apart which kind of Long COVID a person has is important, both to advance our understanding of the illness and to best care for people". 

Review of Long COVID: major findings, mechanisms and recommendations

According to a major review article that has been published in the journal Nature Microbiology, at least 65 million people world-wide are estimated to have Long COVID. The review states that there are likely a multitude of overlapping causes, and the risk factors potentially include female sex, type 2 diabetes, Epstein Barr virus reactivation, the presence of specific autoantibodies, connective tissue disorders, attention deficit hyperactivity disorder (ADHD) and other conditions such as chronic urticaria (medical term for hives) and allergic rhinitis (inflammation of the inside of the nose caused by an allergen). The study states that a higher prevalence of Long COVID has been reported in certain ethnicities including Hispanic and Latino heritage. Socioeconomic risk factors have also been documented which include those with a lower income and the inability to adequality rest in the early weeks after developing COVID-19.  

The association between a healthy lifestyle and Long COVID  

A prospective cohort study (a research study that follows over time a group of individuals who are similar but also differ in certain characteristics) of 1981 women examined the association between following certain modifiable risk factors prior to infection with COVID-19 with the risk of developing Long COVID. The modifiable risk factors included maintaining a healthy BMI (body-mass index), being a non-smoker, consuming a healthy diet, moderating alcohol consumption, engaging in regular exercise and having adequate sleep. The findings revealed that adhering to a healthy lifestyle prior infection with COVID-19 was associated with a ‘substantially’ decreased risk of developing Long COVID.  

Long COVID in Australia – A review of the literature  

Although research on Long COVID is still in its infancy, a recent review has analysed the available Australian and international literature to understand the scale and impact of Long COVID. The review includes the following:  

  1. The incidence and prevalence of Long COVID in Australian and internationally;

  2. Whether SARS-CoV-2 variants and vaccination modify the risk of developing Long COVID; 

  3. Demographic, clinical and social determinants of Long COVID outcomes;  

  4. Outcomes and impact of Long COVID on patients, such as burden of disease, health service use, quality of life and patient experience; and  

  5. Data deficiencies and research gaps around Long COVID.  

Beyond the case numbers: Social determinants and contextual factors in patient narratives of recovery from COVID-19  

An Australian researcher and occupational therapist conducted 37 narrative interviews with adults approximately six months after they had their COVID-19 infection. The findings of the interviews revealed certain themes that had been described by the participants (also referred to as patients). The themes were related to the following: 

  1. Recovery trajectories – about a third of the patients (mostly aged under 30) quickly and completely recovered from acute symptoms; 

  2. Returning to "my normal" – the patients identified as their ultimate recovery destination; and 

  3. Back to work – the patients emphasised that work is a tangible sign of recovery for many.

Exercise

Long COVID and exercise: An updated list of recommendations by the WHO

The WHO strongly recommend that exertional desaturation and cardiac impairment after COVID-19 should be ruled out prior to the re-establishment of an exercise routine. The WHO states: “rehabilitation that involves an increase in oxygen such as in the case of physical activity, in the presence of exertional desaturation or new cardiac impairment, could precipitate an acute event”. The WHO have recommended rehabilitation of post exertional symptom exacerbation (PESE) should involve education surrounding the importance of quality rest and sleep and skills training on energy conservation techniques such as techniques for activity and energy management or pacing. 

A symptom-led approach to exercise during Long COVID recovery  

The UK's National Institute for Health Research has recommended a symptom-led approach to recovery, stating that “the key is to pace yourself by tailoring the volume and intensity of the exercise you do and prioritising rest in between sessions”. They also recommend monitoring symptoms and level of fatigue or post-exertional malaise (chronic symptoms worsening after exertion) during and after exercise to guide amount and intensity. Starting slow with simple movements such as chair-based exercises and once further along in recovery, trying a combination of endurance and strength training, has also been suggested.  

Financial impact

Long COVID and its economic burden

Recent statistics have demonstrated that Long COVID keeps 31,000 Australians away from work each day. This equates to 12% of all COVID-19 related absenteeism. This is also being seen across the world where in the US, there are 4 million people out of the workforce due to Long COVID and in the UK, there 2 million people out of work. Treasurer Jim Chalmers has stated that Australia’s “labour market has been absolutely smashed by COVID-19, and Long COVID increasingly”. 

Vaccination

Does vaccination reduce Long COVID risk?

According to a study conducted on more than 13 million people, vaccination against COVID-19 reduces the risk of developing Long COVID after infection by only 15%. Another study published in The Lancet has found that those fully vaccinated against COVID-19 who developed a breakthrough infection were 49% less likely than those unvaccinated to report symptoms of Long COVID. In terms of Long COVID symptom improvement post vaccination, a survey found that approximately 40% of respondents with Long COVID documented an improvement in their symptoms after vaccination however another 14% stated that their symptoms had worsened. Overall, vaccines do appear to reduce the symptoms of Long COVID but further evidence is required.

Vaccine now deemed effective against the development of Long COVID based on meta-analysis – December 2022

A new meta-analysis conducted on vaccine effectiveness against Long COVID has shown that getting at least one dose of a COVID-19 vaccine (Pfizer, Moderna, AstraZeneca or the Janssen vaccine) decreases the chances of having symptoms beyond three weeks or developing Long COVID. The vaccine has been deemed effective in reducing post-COVID-19 conditions even after having COVID-19. The authors states that “although some patients who previously contracted COVID-19 are hesitant to get vaccinated, our findings can reassure that individuals with prolonged COVID-19 symptoms who have not been vaccinated that they should do so”. 

Research study finds that vaccination reduces the risk of Long COVID - March 2023

A recent study has demonstrated that compared to vaccinated patients, unvaccinated patients were 7 times more likely to develop Long COVID. Authors of this research paper state that it is imperative to promote vaccination and implement education campaigns to inform the public about the risks and consequences of Long COVID.

Children

Children developing multisystem inflammatory syndrome post COVID-19 infection – what parents should look out for

Paediatric inflammatory multisystem syndrome (PIMS-TS) is a rare condition that has been demonstrated to manifest among children after infection with COVID-19. Statistics have estimated that roughly one in every 2,500 children who contract COVID-19 are affected by the syndrome. This condition begins within 6 weeks after COVID-19 infection and is characterised by an inflammatory response that occurs within several different parts of the body. Signs and symptoms usually include fever (for more than 3 days), vomiting, diarrhoea, abdominal pain, headaches, conjunctivitis, rashes, swollen lymph glands, sore throat and a cough. It has been recommended that if your child has a fever that continues for more than three days in the 2 to 6 weeks after COVID-19 infection, it is best to seek medical advice. Although treatment is available, at this stage, up-to-date vaccination status remains the best form of protection against this syndrome.

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