Top picks: 12 research papers on Long Covid

Summary

We are seeing more and more people who have been devastated by the long-lasting impact of Covid-19. Long Covid is a relatively new condition which is still being studied and the need for more awareness and advocacy has never been greater.

Scientists are carrying out large-scale clinical trials and researchers are on the hunt for new therapies in the hope that patients with Long Covid will finally see improvements in treatment and support for their symptoms.  In this Top picks blog, shared on International Long Covid Awareness Day, we highlight 12 recent research papers on Long Covid. 

Content

Long Covid can affect anyone exposed to SARS-CoV-2 (Covid-19) and is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Studies show that around 10–20% of people infected by SARS-CoV-2 may go on to develop symptoms that can be diagnosed as Long Covid (WHO, 2022).

While common symptoms of Long Covid can include fatigue, shortness of breath and cognitive dysfunction, over 200 different symptoms have been reported that can have an impact on everyday functioning. The following open access studies highlight key research on Long Covid.

1 Core outcome measurement instruments for use in clinical and research settings for adults with post-Covid-19 condition: an international Delphi consensus study

Researchers have identified a Core Outcome Measure Set (COMS). This is designed to help researchers and clinicians measure the severity and impact of Long Covid. COMS specify key things that should be measured in all patients. This improves how data can be compared and summarised. Researchers say this will speed up the development of treatments for Long Covid. 

2 Long Covid: confronting a growing public health crisis

In this Lancet Respiratory Medicine Series, Sally J Singh and colleagues discuss the origins of respiratory sequelae and consider the promise of adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management. Pratik Pandharipande and colleagues review the epidemiology and pathophysiology of neuropsychological sequelae of Covid-19-related critical illness, highlighting the combined threat of Long Covid and post-intensive care syndrome (PICS), and outline potential mitigation strategies. Finally, Matteo Parotto and colleagues discuss pathophysiological mechanisms of diverse, multisystem sequelae in adult survivors of critical illness, including longitudinal effects of endothelial and immune system dysfunction, and consider the challenges of providing appropriate care and support for patients.

3 Cognition and memory after Covid-19 in a large community sample

Poor memory and difficulty thinking or concentrating (commonly referred to as “brain fog”) have been implicated in syndromes occurring after Covid-19 — a situation that has led to suggestions that Covid-19 may have lasting cognitive consequences. In this observational study in the New England Journal of Medicine, 800,000 adults in England were invited to complete an online assessment of cognitive function. The authors estimated a global cognitive score across eight tasks. They found objectively measurable cognitive deficits that may persist for a year or more after Covid-19. Participants with resolved persistent symptoms had small deficits in cognitive scores, as compared with the no–Covid-19 group, that were similar to those in participants with shorter-duration illness. Early periods of the pandemic, longer illness duration, and hospitalisation had the strongest associations with global cognitive deficits. 

4 Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

This study, published in Science, compared the blood of patients with confirmed Covid-19 infection with that of uninfected controls. The authors found that there were changes to serum proteins in the blood of patients experiencing Long Covid. This indicates activation of the immune system’s complement cascade, altered coagulation and tissue injury. At the cellular level, Long Covid was linked to aggregates comprising monocytes and platelets. These findings provide knowledge of potential biomarkers for diagnosis and may inform directions for treatments.

5 Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-Covid-19 condition (REGAIN study): multicentre randomised controlled trial

This study, published in the BMJ, evaluated whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with Long Covid. Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. The authors concluded that in adults with Long Covid, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at 3 and 12 months compared with usual care.

6 The immunology of Long Covid

This review, published in Nature Reviews Immunology, looks at the research and data relating to Long Covid, including symptoms, possible mechanisms of Long Covid, long-term disease risk following Covid-19, therapeutics and outlook. 

7 Long Covid: major findings, mechanisms and recommendations

This research paper, published by Nature Reviews Microbiology, explores the current knowledge base of Long Covid as well as misconceptions surrounding Long Covid and areas where additional research is needed. It looks at diagnostic tools and treatments, the impact of vaccines, variants and reinfections, and recommendations for research, training and education.

8 Something in the blood II: Long Covid/fibromyalgia autoimmune connection found

This blog focuses on a poster presented at the World Congress on Pain in Toronto in 2022 and discusses the connection between Long Covid and fibromyalgia.

9 New evidence suggests Long Covid could be a brain injury

Brain fog is one of the most common, persistent complaints in patients with Long Covid, affecting up to 46% of patients, many of whom also deal with other cognitive concerns like memory loss and difficulty concentrating.  This Medscape article looks at new research suggesting these symptoms may be the result of a viral-borne brain injury that causes cognitive and mental health issues that persist for years. This may offer new options for treating brain fog and other cognitive symptoms associated with Long Covid.

10 The effectiveness of Covid-19 vaccines to prevent Long Covid symptoms: staggered cohort study of data from the UK, Spain, and Estonia

This cohort study in the Lancet evaluated the overall effect of vaccination to prevent Long Covid symptoms and assessed comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). The results showed that vaccination against Covid-19 consistently reduced the risk of Long Covid symptoms, which highlights the importance of vaccination to prevent persistent Covid-19 symptoms, particularly in adults.

11 Postacute sequelae of COVID-19 at 2 years

In this study, published in Nature Medicine, a cohort of 138,818 individuals with Covid-19 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs were followed for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of Covid-19— including cardiovascular disorders, neurologic and mental health disorders and metabolic disorders—according to care setting during the acute phase of infection. The study found that while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to postacute sequelae of Covid-19 calls for attention to the care needs of people with long-term health effects due to Covid-19.

12 Large-scale phenotyping of patients with Long Covid post-hospitalization reveals mechanistic subtypes of disease

This study published in Nature Immunology aimed to understand inflammatory processes that underlie Long Covid. The findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of Long Covid, which might be targeted in future therapeutic trials.

Further reading on the hub:

• Time to confront Long Covid: An interview with Clare Rayner on why we must keep pushing for research, treatment and prevention

You can find further Long Covid resources, blogs and information on the hub here.