Long Covid: why do some people have symptoms months after infection?
Long Covid is another public health crisis hidden inside the pandemic, medical experts have warned, with estimates of the patients suffering from the debilitating disease stretching to more than 100m worldwide.
Scientists are in the early stages of hunting for treatments that could ease symptoms, target the still unclear causes, and get people healthy enough to return to work.
A meta-analysis of studies by Penn State researchers found more than half of the 236m people who had Covid-19 when the paper was published — which has since risen to 275m — had symptoms lasting more than six months.
Amitava Banerjee, a professor of clinical data science at University College London, said even two years into the pandemic, we are “still caught in the headlights”, focused on dashboards that track intensive care admissions and deaths — but not the long Covid crisis.
How is long Covid defined?
Long Covid is defined as suffering symptoms 12 weeks or more after diagnosis.
A recent UK study discovered one in three of those admitted to hospital were suffering from long Covid a year later. Rachael Evans, a clinical scientist at the UK’s National Institute for Health Research, said the post-hospital admission Covid-19 study helped sort sufferers into subgroups and steered work to discover new drugs.
“It really highlights the urgent need for treatments to be investigated and for healthcare support to improve recovery,” she added. “None of us think that long Covid has one mechanism and one treatment.”
What are the symptoms of long Covid?
While patients suffer a range of symptoms, the most commonly reported are fatigue and breathing problems. Some also experience damage to their organs and in the PHOSP study, one in 10 had clinically relevant cognitive impairment, often called “brain fog”. Many symptoms resemble those in other post-viral diseases, including from coronaviruses.
Margaret O’Hara, a trustee at patient group Long Covid Support, fell sick with Covid-19 in April 2020, after assisting on a critical care coronavirus ward. She experienced long Covid for a year — and then, after contracting the disease in October 2021, is suffering again.
“Just fatigue doesn’t really begin to describe the intensity,” she said. “It’s so bizarre. Sometimes I’ll get up in the morning and within an hour it is like I’ve been anaesthetised. Like someone put a chloroform hanky over my mouth and I have to go lie down.”
Women, people with obesity, and those who were on invasive mechanical ventilation are all more likely to develop long Covid.
It is not clear the degree to which vaccination helps prevent long Covid — other than reducing the likelihood of developing acute Covid-19 — but self-reported data from the UK’s Zoe symptom tracking app suggest it halves the risk.
What causes long Covid?
A great deal remains unknown. However, the PHOSP study provided an important clue that lends weight to a hypothesis that long Covid is caused by a continued immune reaction. It found sufferers had increased inflammatory markers. Researchers discovered that the people with the most severe long Covid, and those experiencing brain fog, had the highest levels of inflammation.
Sir Stephen Holgate, University of Southampton professor and co-founder of Synairgen, a company that is creating Covid-19 antiviral medication, said MRI scans had also shown inflamed organs.
“The body turns on itself as a result of all this inflammation during the Covid period and attacks its own tissue.”
There may be a genetic predisposition that determines who is most likely to suffer this kind of immune response, so researchers are conducting large genome-wide association studies that try to locate genes that patients have in common.
Another hypothesis is that the virus attacks the cells’ energy reserves, mitochondria. Sub-groups could be suffering for different reasons — or both hypotheses could be true at once.
Are there drugs that could be repurposed?
The UK’s NHS and large US health systems have established long Covid clinics, which often offer physiotherapy and mental health support, but so far have not had many pharmaceutical options.
Some physicians have been trying to use drugs with few side-effects that they believe could have an impact. These are as diverse as the symptoms, including antihistamines and cytokine blockers to address inflammation, antacids, beta blockers and anti-clotting agents. A recent small Cambridge study suggested taking a combination of “friendly bacteria” could help ease long Covid’s gut symptoms and improve overall wellbeing.
Banerjee aims to start a study in the new year, modelled on the Recovery Trial that helped identify useful drugs for treating acute Covid-19.
What are the future drugs in development?
Bill Hinshaw, chief executive of Boston-based biotech Axcella Therapeutics, said there were few products in the pipeline for long Covid — and even fewer targeting muscle fatigue and weakness. Axcella and Oxford university are developing a drug to reduce inflammation and restore mitochondrial function. They hope to have clinical trial data in the middle of this year.
“You have a certain amount of energy in the battery,” said Hinshaw. “The virus comes in and takes over the battery and . . . damages it so the battery can no longer hold the charge properly.”
Others are focusing on a subset of patients. For example, digital therapeutics pioneer Akili Interactive is creating a game for people suffering from brain fog.
PureTech Health is working on a drug for lung tissue damage, which is in a phase 2 trial. Michael Chen, head of innovation at the London-listed biotech, said almost half of those with long Covid experienced breathlessness, so “millions and millions” could have lung scarring.
“It’s a little bit of a terrifying thought and a window into the public health crisis that could be long Covid in the future.”