Four years since the start of the pandemic, a significant number of individuals continue to suffer greatly, with symptoms lasting for up to two, three, or even four years following their initial infection with the virus.

The Earth now boasts a significant new field in medicine focused on those persistently ill,” states Danny Altmann, an immunology professor at Imperial College London. “The estimates vary widely but suggest that anywhere from 65 million to 200 million individuals continue to suffer from long-term effects of COVID-19. This number could potentially populate entire hospital wards across all cities globally.

According to the recent report released by the Office of National Statistics in March, approximately 3.3% of individuals in England and Scotland are experiencing long-term effects of COVID-19. Among them, 71% have reported having symptoms for one year, 51% for at least two years, and 31% for a minimum of three years. This last group includes around 750,000 people; however, due to the lack of a specific diagnostic test for long COVID, these statistics rely entirely on self-reporting.

Cat Rowles, aged 40, who once worked as a children’s and adolescents’ nurse for the NHS, caught Covid during the spring of 2020. She initially experienced fatigue, drowsiness, and shortness of breath—symptoms she found odd since she would usually cycle everywhere without difficulty and climb flights of stairs effortlessly before this.

I attempted to go back to work but found myself unable to manage physically, eventually leading me to be confined to my bed for several months. Starting from the summer of 2020, I have been dealing with extreme exhaustion and increasing mental confusion so severe that forming complete sentences became challenging. Simple tasks like brewing a cup of tea were forgotten.

Rowles experimented with various typical supplements to ease her symptoms: she took multivitamins, probiotics, and even used nicotine patches for some time based on a minor study indicating potential benefits for reducing fatigue. “What truly made an impact was adopting a highly nutritious diet devoid of refined sugars, gluten, and alcohol, alongside minimal processing of foods, combined with periodic fasting and two full-day fasts each week. This regimen has aided me in maintaining my current level of activity. However, working remains out of reach.”

Even now, she continues to be unwell. “There are days when I find it hard to walk more than a few meters, and these severe episodes can persist for over a week. Despite being fortunate that my family, friends, and partner have been supportive, it feels like I’ve lost four years of my life.”

Can long COVID be misidentified as another condition?

Many patients have undergone gaslighting at the hands of doctors and other healthcare providers who often believe that their condition is rooted in mental health issues.

Manoj Sivan, a consultant in rehabilitation medicine and professor at the University of Leeds, who has been heading a long COVID research project named Locomotion, mentions that numerous individuals get incorrectly diagnosed with depression, anxiety, or chronic pain.

There remains skepticism regarding the condition, and healthcare providers do not consistently refer these patients to long COVID clinics,” he explains. “As a result, these individuals often get told, ‘This is merely an intensification of your anxiety; it’s a response to what you’re experiencing in your daily life.’

Wendy Crawford, aged 47, who works as a finance officer, contracted Covid four years ago and has not fully recuperated since then. “I must have invested thousands of dollars seeking out various consultations, tests, and treatments in an effort to address my condition,” she says.

In Scotland, individuals suffering from long COVID continue to face the same narrative from authorities. They advise visiting general practitioners, who subsequently direct them to different clinics. These specialized long COVID clinics aren’t led by doctors; instead, they simply present slide shows about symptom management conducted by physiotherapists and occupational therapists, followed by discharge after twelve weeks.

Although most research indicates that using antiviral treatments during a severe case of Covid can offer some defense against developing long-term symptoms later on, numerous individuals find it difficult to access these drugs through the National Health Service. Crawford mentions that even after enduring a lengthy sickness, she hasn’t managed to secure antiviral medication aimed at preventing future episodes.

“My previous reinfection left me bedridden for more than a year. However, when I attempted to obtain antiviral treatment after testing positive again, I was informed that it wasn’t an option because I wasn’t considered part of a vulnerable group,” she explains.

David Putrino, an associate professor at New York’s Mount Sinai Health System, who studies long COVID, remains optimistic about the potential of new AI-based diagnostic tools reaching medical practices. These tools could help perplexed physicians distinguish between long COVID cases and mental health disorders more effectively, as well as offer insights into therapeutic approaches that may be beneficial.

In the previous year, he introduced a novel model capable of accurately distinguishing between individuals suffering from Long COVID and those with different ailments, based on the concentrations of multiple hormones and immune cells. He explains, “Once an algorithm diagnoses each patient, the specific factors contributing to their particular diagnosis can subsequently inform their treatment plan.”

What are the indicators and manifestations of long COVID?

Long COVID is a multifaceted illness characterized by numerous complexities, leading to widespread confusion and skepticism surrounding the ailment. Various reports suggest over 200 distinct symptoms are linked to this condition.
a 2023 study
in the journal
Nature Reviews Microbiology
.

These symptoms can affect the brain, heart, lungs, and various internal organs, as well as the vascular system, digestive tract, and even the reproductive system.

Patients often report experiencing extreme tiredness and mental cloudiness along with issues related to their autonomic nervous system, which controls heart rate and blood pressure. This can make standing up an ordeal, frequently leading to dizziness and discomfort.

However, certain patients might encounter uncommon and strange symptoms that emerge in various parts of their body, ranging from abrupt allergic responses to blood clotting issues. These manifestations may include ongoing mild fever to hearing disorders like tinnitus.

Melanie Morby, aged 62, a previous community nurse with experience in running half marathons, reports experiencing joint pain, migraines, and shortness of breath following her third bout of Covid-19 infection. She explains, “This constant exhaustion never leaves me; every activity feels like wading through thick syrup.”

Professor Putrino states that the vast range of varying and intersecting symptoms observed in patients has made researching this condition extremely difficult.

Some individuals experience issues with their immune system, others face problems related to blood vessels or imbalances in gut bacteria, and unfortunately, some encounter all of these conditions simultaneously,” he explains. “It has become clear that an acute SARS-CoV-2 infection can set off various long-term health complications.

What factors lead to prolonged COVID-19 symptoms?

Much like how the specific set of symptoms can differ significantly between individuals, so too can the root causes vary widely. Researchers currently think that certain patients might carry leftover fragments of the SARS-CoV-2 genetic code hidden away in distant parts of their body—such as within the brain and spinal cord—for several years following the initial infection.

However, for some individuals, even though the virus might be gone, its early appearance could have been enough to trigger an excessive immune reaction. This can lead to a scenario where the body’s defense mechanisms continue to attack its own tissues due to an ongoing autoimmune response.

Prof Sivan has witnessed
numerous studies
indicating that individuals with long COVID exhibit elevated levels of autoantibodies. Unlike regular antibodies which target foreign substances, these autoantibodies mistakenly assault the body’s own cells, tissues, and proteins.

Prof Putrino states, “The severe Covid infection could initiate an excessive immune reaction that has not subsided. As a result, the body continues to maintain a constant and unending defense mechanism against what it perceives as an ongoing threat.”

What causes these immune reactions to produce symptoms?

Research suggests that in numerous instances, long COVID might fundamentally be considered an autoimmune disorder driven by autoantibodies. Professor Putrigo and his colleague Professor Akiko Iwasaki from Yale University have carried out an as-yet-unpublished research showing evidence that these autoantibodies could be responsible for several of the condition’s manifestations.

During a recent talk, Iwasaki explained their process of collecting blood samples from people with long COVID and from those without the condition. They then isolated immunoglobulin G (IgG), a protein capable of functioning as both an antibody and an autoantibody, and administered this substance to laboratory mice. Within merely six days, the rodents that were given IgG derived from long COVID sufferers exhibited problems with balance, muscle weakness, and indications of persistent pain. In contrast, the mice receiving IgG from healthy subjects showed no symptoms at all.

This indicates that there is a portion of individuals suffering from long COVID who undoubtedly exhibit certain autoimmune characteristics which can spread,” explains Professor Putrino. “This implies that for at least some cases, specific immunotherapy treatments might serve as a method to deactivate these autoantibodies.

Who is at highest risk of developing long COVID?

We continue to explore the reasons behind why certain individuals are more susceptible to long COVID, and Professor Sivan notes that vaccines have shown significant protection against it.

There is a distinct trend showing individuals who acquired long COVID during the initial wave, prior to the introduction of vaccinations, experienced worse outcomes,” he explains. “However, after someone develops long COVID, vaccines offer very limited protection. While they lessen the severity of subsequent infections, they cannot reverse the harm that has already occurred.

Based on Professor Sivan’s observations, individuals from a lower socioeconomic background or those who had prior health conditions affecting their immune systems appear to have been significantly more susceptible to experiencing prolonged symptoms of COVID-19.

We’ve observed that individuals in their middle years, who hold down demanding jobs, return to work before fully recuperating and subsequently face difficulties,” he explains. “This indicates that their immune systems haven’t had time to heal properly; instead, they get continually stressed, leading to repeated breakdowns.

Ways to handle symptom management

Currently, the restricted treatment choices available at long COVID clinics primarily focus on alleviating or concealing patients’ symptoms rather than providing curative solutions.

Regarding extreme tiredness, Professor Sivan advises concentrating on pacing oneself and remaining within one’s personal energy boundaries to prevent setbacks. For patients exhibiting signs of mast cell activation syndrome—a disorder that can arise after an allergic response—such as hives, swelling, reduced blood pressure, and respiratory issues, doctors may prescribe antihistamines to control these episodes.

Professor Sivan’s research has concentrated on addressing the symptoms of autonomic nervous system disorders encountered by numerous patients, including lightheadedness, decreases in blood pressure, and increases in heartbeat upon standing.

You administer medications to regulate heart rate and boost blood pressure, along with other tactics like enhancing fluid and sodium consumption, and we’re achieving excellent outcomes,” he states. “Individuals begin feeling more energetic, which enhances their productivity since it diminishes the mental fuzziness.

In the upcoming years, new therapies explicitly designed to tackle fatigue might be introduced. These could include medications or supplements intended to repair some of the harm done to the mitochondria—the cell’s energy-producing components—either by the virus itself or as part of an ensuing autoimmune reaction. This was mentioned regarding developments from last year.
a clinical trial
A study carried out by scientists from the University of Oxford revealed that an amino acid mixture created by pharmaceutical firm Axcella Therapeutics indicated potential in reducing tiredness among individuals suffering from Long COVID.

Is there a treatment for long COVID?

Due to the intricacies involved, Professor Putrino states that discovering a universal remedy for long COVID is impractical. He emphasizes that the emphasis should instead be on categorizing patients into different groups based on their likelihood of responding positively to various treatments.

This is especially crucial since research has shown that the antihistamine famotidine may help alleviate brain fog in some individuals, whereas another study revealed that combining L-arginine with vitamin C could enhance workout endurance. Nevertheless, we remain largely unclear about what makes specific patients react positively to these treatments while others do not.

For instance, Professor Putrino refers to another study where participants who took both coenzyme Q10 and alpha lipoic acid together saw their fatigue completely disappear within two months. He explains, “We can only inform them that they have a 50% likelihood of success with this approach.” He adds, “This isn’t much of a gamble from a monetary standpoint for many patients since dietary supplements come at considerable cost and aren’t covered under the National Health Service.”

As trials globally explore the effectiveness of stronger medications like immunotherapies and wide-ranging antivirals, Professor Putrino argues that improving patient screening methods is crucial. This would help determine which individuals could potentially benefit from these treatments and which ones might face risks instead.

How might things appear in the future?

Professor Altmann indicates that although the UK was more advanced than numerous countries in acknowledging the issue of long COVID back in 2020, setting up specialized clinics nationwide, and investing funds in research via the National Institute for Health and Care Research (NIHR), this progress has not just halted but has actually reversed course.

Although the NIHR originally supported 19 multi-year investigations into long COVID, all these projects were scheduled to conclude by June. Moreover, the prolonged survival of specialized centers remains uncertain, particularly since the financing for the UK’s 100 long COVID clinics is under scrutiny and may not be assured past March 2025.

We have all the correct intuitions regarding potential treatments for these individuals, be it antivirals, immune modulators, or anticoagulants—name it,” states Professor Altmann. “Yet, despite this, we struggle to gain traction in implementing these measures. Meanwhile, people are desperately awaiting help, and we’re nearly within reach of providing viable options.

Recommended

Why ‘long COVID’ remains taboo: My acquaintances simply ignore it

Read more

Subscribe to the Front Page newsletter at no cost: Your daily roadmap from The Telegraph, delivered directly to your mailbox every single day of the week.