In the early days of the Covid-19 pandemic, when we knew very little about the natural history of the virus, groups of patients started to report long-lasting symptoms. This was termed Long Covid or Post-Acute Covid Syndrome (PACS), and it posed great uncertainty for both clinicians and patients, particularly as case numbers rose.

I was one of a group of UK doctors experiencing Long Covid who formed a social media group to make sense of our own experiences. This helped us to identify patterns of ill-health and share knowledge. In mid-2020, we published medical articles about the patterns of symptoms that many people were experiencing.

The birth of a transatlantic collaboration – the PACS International Working Group

In August 2020, at a World Health Organization (WHO) meeting, Dr Amali Lokugamage and I were asked by UK patient support groups to explain the medical effects of Long Covid. The meeting was arranged by WHO in response to requests by patient groups for help. They asked WHO to ‘Recognise, Research and Rehabilitate’ Long Covid. To this, Amali and I added a fourth R: ‘Return to work’, as we saw the negative impact of Long Covid on people’s employment. 

Following this meeting, I made a connection with Dr David Putrino, Director of the Department of Rehabilitation Innovation at Mount Sinai Health System. He shared our concerns about the health, work and economic implications of Long Covid. 

In an article that reported on the WHO meeting, Dr Putrino said, “What we need to do is rapidly mobilise and educate people that Long Covid is a real thing, and it’s going to be around for a while. There's a lot of hurt and we are doing what we can to help, but we need a lot of people to pick up the torch and run with us.”

Dr Putrino’s objective was not just to get WHO and the United States Center for Disease Control (CDC) to recognise the longer term health impacts of Covid-19, but also to acknowledge that the condition was occurring in a vast number of people, many with negative PCR and antibody tests. In the US, people were being denied insurance payments for healthcare and disability payments on these grounds. In the UK, people were – and still are – facing similar difficulty in accessing healthcare, support to stay in work and disability benefits. We also shared concerns that patients who hadn’t been hospitalised were being ignored despite experiencing prolonged illness.

The Rehabilitation Innovation Department at Mount Sinai Hospital had set up the world’s first clinic for rehabilitation of non-hospitalised PACS patients. Due to the number of Covid cases in New York, they were also the first to develop a way of monitoring acute cases at home when the hospitals had no space. The US team was working flat-out seeing patients, and lacked the time or manpower to get their knowledge of the condition out more widely.

So we decided to pick up the torch and help meet the urgent need to write information to educate clinicians around the world about Long Covid. Amali and I consulted our Doctors with Long Covid Facebook group, which had around 350 members at the time and was discussing and collecting a database of research. We recruited a few doctors who were also experienced educators.

Global teamwork powered by Zoom and social media

We met at an initial Zoom meeting, where members from the Mount Sinai medical and rehabilitation teams described the health problems they were seeing as a result of Long Covid and how they were treating them. Their expertise in inherited and autonomic cardiovascular disorders meant that they had recognised important patterns of autonomic dysfunction early in the pandemic. On the UK side, we were medically qualified volunteers with diverse skills in general practice, hospital medicine, child health, psychiatry, sports medicine and physiotherapy. Some of us were experiencing Long Covid ourselves and some were running post-Covid clinics.

We agreed that Mount Sinai would provide their data and knowledge from managing PACS, while the UK team would use our medical expertise, lived experiences and skills as communicators to produce a trustworthy stream of educational information for patients and healthcare workers.

The key aim of the group was to create educational networks and resources in order to:

1. increase awareness of Long Covid
2. inform research and clinical practice
3. provide both patients and clinicians with key concepts to help manage the patterns of illness, both in the UK and the US.

Outputs of the collaboration

We met monthly on Zoom from August 2020 to discuss emerging health problems. Together, we identified the dominant health problems in Long Covid rehabilitation, and began to learn how to manage them. The US team noted that ‘standard’ rehabilitation and exercise approaches caused worsening. They developed schemes to take account of the dominant autonomic nervous system dysfunction and modified their assessment tests. 

Over time, we brought information from New York to the UK about the most adverse health problems caused by Long Covid:

• Autonomic Dysfunction - how to recognise triggers and manage it.
• Neurocognitive problems.
• Severe debility, more than with other viruses. People with Long Covid absolutely cannot exercise at first and should start with breathing exercises.
• Sense of trauma - the emotional impact of lack of access to healthcare, or not being believed.

We disseminated this information through regional and national committees organising Long Covid care in the UK, but these messages were not taken on board. Cascade learning has been more effective in getting key messages across, through our now thousand-member Doctors with Long Covid group, and other patient groups. Some clinicians that have returned to work are also sharing information and good practice.

The UK team created an online repository of research papers on Long Covid pathology and management of health issues, which was used by Mount Sinai staff and patients. We wrote information leaflets and publications for UK and US use and shared them on a website hosted by Mount Sinai, including ‘Men and Long Covid’, ‘Top tips for general practice’, ‘You don’t need a positive test’, ‘Covid and voice problems’ and ‘Returning to work after Covid-19’. We took part in Mount Sinai’s cognitive rehabilitation programme and they shared their research outcome data on various topics.

We all contributed to the World Physiotherapy Association Briefing document for safe rehabilitation in post-Covid syndrome, and some of us are currently part of the WHO Guideline Development Group on PACS Rehabilitation. In 2021, we jointly took part in webinars for the UK Society of Occupational Medicine, and spoke at WHO and UK multidisciplinary clinical meetings.

Barriers to progress in understanding and treating Long Covid

It has been frustrating having spent a year trying to share learning, only for it to be ignored. A year after we first shared our findings on the subject in September 2021, senior respiratory clinicians finally admitted that pulmonary rehabilitation techniques designed for other conditions do not work in Long Covid.

The UK has focused on reinventing the wheel and not getting it turning, and this has led to a delay in people with Long Covid receiving appropriate advice. We have seen first-hand how collectively loud the patient voice has had to be, to be listened to.

Ongoing transatlantic collaboration and support

It has, however, been energising to work in collaboration, solving problems and using investigative skills to develop effective and safe rehabilitation techniques. The PACS group continues to meet, pulling in different people as required, and we see the potential for future research collaborations. We also continue to support and communicate each other’s constructive messages via social media.

Our collaboration of lived experience, professional expertise, collective action and determination to deliver rapid learning and treatment is an unexpected benefit of the challenging circumstances we have faced during this pandemic.

Related reading
The mythology of Long Covid - 9 common misconceptions
Promises of Long Covid support have not materialised (a blog by Clare Rayner)
My experience of suspected 'Long COVID'
Long Covid: Information gaps and the safety implications (7 June 2021)
Children with Long Covid: Co-producing a specialist community public health nursing response (19 October 2021)
How will NHS staff with Long Covid be supported?

Despite Long Covid being a burgeoning health concern, the risk factors and pathophysiology remain obscure. The varied clinical presentation of Long Covid poses a diagnostic challenge to clinicians. In order to establish a framework for better clinical decision making, understanding the complex nature of Long Covid is essential.

WHO definition 

The World Health Organization (WHO) defines Long Covid as ‘Post Covid-19’, a condition that occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually beginning within three months of the initial onset of Covid-19.[2]

Some common symptoms are fatigue, shortness of breath and cognitive dysfunction, but there are many others. The symptoms may have new onset or persist from the time of initial infection, lasting for at least two months. They cannot be explained by an alternative diagnosis. 

Who is at high risk? 

The US Centers for Disease Control and Prevention noted that people with higher body mass index, those above 40 years of age and those with pre-existing medical conditions are at higher risk of developing Long Covid.[3] Women are at increased risk due to intense immune responses influenced by genetic and hormonal factors  [4], and certain ethnic groups are more prone to develop Long Covid than others.

Recent reports show both hospitalised and non-hospitalised Covid patients experience Long Covid.[5] However, patients with severe disease and those who have more than five symptoms during their first week of illness are at greater risk.[6]

What causes Long Covid? 

The precise mechanisms causing Long Covid are unknown, and are likely to be multifactorial. Plausible mechanisms that could differ or co-exist among individuals, are: 

• virus-specific pathophysiological changes like endothelial damage, and micro-vascular injury. 
• maladaptation of Angiotensin Converting Enzyme 2 (ACE2) pathway leading to abnormal autonomic, endocrine, metabolic and neurological functions. 
• autoantibodies provoking chronic inflammation and long term Covid-19 sequelae. 
• expected sequelae of post-critical illness such as new or worsening abnormalities in physical, cognitive and psychiatric domains.[7]

In addition, alterations in host microbiome [8], and presence of persistent SARS-CoV-2 reservoirs in tissues [9] like gut, liver, gall bladder and lymph nodes could trigger long-term morbidity. 

How to treat Long Covid? 

Long Covid has no specific clinical presentation and the symptoms often fluctuate and vary between individuals. Hence, a holistic and multidisciplinary approach is essential for the treatment of Long Covid.[7]

The first step is careful evaluation of the symptoms and comprehensive clinical assessment of the patient’s history. Based on the initial evaluation, investigations like chest X-ray, blood tests, electrocardiogram (ECG) and exercise tolerance tests should be performed to distinguish from other possible diagnoses. 

In the next step, depending on the severity of the symptoms, individualised treatment plans should be devised. Symptoms including cough, fever, generalised body pain and fatigue are treated symptomatically. On the other hand, critically ill patients with signs of severe lung disease, cardiac chest pain, coagulation issues or psychiatric symptoms require close monitoring with intensive treatment. In general, patients affected by Long Covid need psychological support as well as physical rehabilitation care.

How do vaccines prevent Long Covid? 

There is evidence that vaccination plays an important role in alleviating the impact of Long Covid. According to some studies, vaccinated individuals are around 50% less likely to develop long Covid [10] than unvaccinated individuals. Recent studies show that priming the immune system with Covid-19 vaccines enhances immunity towards SARS-CoV-2 virus [11], thereby eliminating the viral reservoirs. Vaccines also help prevent persistent dysregulated immune response, limiting the chronicity of the disease.

Ways forward in preventing and treating Long Covid

The impact of Long Covid is unparalleled, and the condition remains enigmatic. To mitigate the effects of Long Covid, understanding the pathogenesis, risk factors and clinical presentation is important. Preventive measures like vaccination, social distancing and consistent use of masks should be diligently followed. Lastly, reinforcing the 4 R’s – Reporting, Recognition, Rehabilitation and Research – could reduce the burden of Long Covid.

Related reading

The mythology of Long Covid - 9 common misconceptions (20 December 2021)
Long Covid: Information gaps and the safety implications (7 June 2021)
Long Covid podcast: Claire Hastie - founder of Long Covid Support, & advocate (10 November 2021)

References

1 D Altmann, R Boynton. Decoding the unknowns in long covid. BMJ. 2021;372:n132
2 A clinical case definition of post COVID-19 condition by a Delphi consensus. World Health Organization. 6 October 2021
3 K Yomogida, S Zhu, F Rubino et al. Post-Acute Sequelae of SARS-CoV-2 Infection Among Adults Aged ≥18 Years — Long Beach, California, April 1–December 10, 2020. MMWR Morb Mortal Wkly Rep 2021;70:1274–1277
4 E Ortona, D Buonsenso, A Carfi et al. Long COVID: an estrogen-associated autoimmune disease?. Cell Death Discov. 2021;7:77
5 A Mohamed-Hussein, M Amin, H Maklouf et al. Non-hospitalised COVID-19 patients have more frequent long COVID-19 symptoms. International Journal of Tuberculosis and Lung Disease. 2021;25:9:732-737
6 C Sudre, B Murray, T Varsavsky et al. Attributes and predictors of long COVID. Nat Med. 2021;27;626–631
7 H Crook, S Raza, J Nowell et al. Long covid—mechanisms, risk factors, and management. BMJ. 2021;374:n1648
8 Y Kit Yeoh, T Zuo, G Chung-Yan Lui et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70:698-706 
9 V Marx. Scientists set out to connect the dots on long COVID. Nat Methods. 2021;18:449–453
10 V Tran, E Perrodeau, J Saldanha et al. Efficacy of COVID-19 Vaccination on the Symptoms of Patients With Long COVID: A Target Trial Emulation Using Data From the ComPaRe e-Cohort in France. Preprint available at SSRN: https://ssrn.com/abstract=3932953
11 H Ledford. Do vaccines protect against long COVID? What the data say. Nature, 23 November 2021