Doctors in India face challenges treating long Covid amid research gaps

Doctors in India are grappling to diagnose and treat unexplained and persistent symptoms of long Covid patients due to limited guidelines, whereas researchers have flagged inadequate studies on the condition.

With the World Health Organization declaring an end to Covid as a global health emergency in May last year, focused efforts are underway around the world to estimate the burden of long Covid among the population.

The condition refers to the set of lingering symptoms affecting varied body parts and persisting well beyond the acute Covid infection period, including cough, muscle and joint pain, fatigue, brain fog and difficulty in focusing. The viral disease is caused by the SARS-CoV-2 virus.

While studies have suggested that about a third of those moderately or severely infected are likely to suffer from long Covid, region-wise though, incidence could vary.

A study by researchers, including those from Harvard Medical School, US, estimated that 31 per cent of the once-infected people in North America, 44 per cent in Europe, and 51 per cent in Asia, have long Covid, which is "challenging the healthcare system, but there are limited guidelines for its treatment". It was published in the International Journal of Infectious Diseases in September.

In India, however, studies on long Covid are few and far between.

One such study by Maulana Azad Medical College in New Delhi, conducted from May 2022 to March 2023 on 553 patients who had recovered from Covid, found that about 45 per cent had lingering symptoms, persistent fatigue and dry cough being the most common.

"There is limited exploratory research on the long Covid syndrome with scarce data on long-term outcomes," the authors wrote in the study published in the journal Cureus in May this year.

Understanding the long-term effects of the virus is important for developing management strategies, optimising healthcare delivery, and providing support to recovered Covid patients in the community, they said.

Dr Rajesh Sagar, Professor of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, said, "Looking at the current state of long Covid studies in India, it is too premature to say that we understand the condition well enough to know how to diagnose or treat it."  Animesh Samanta, assistant professor at School of Natural Sciences in Shiv Nadar University, Greater Noida, said, "While studies in India highlight the growing recognition of neurological complications in long Covid patients, more focused research on neuroinflammation is needed."  Doctors, too, have reported a rise in patients complaining of symptoms that they did not have pre-Covid.

"People who never had asthma in the past, post-Covid, with every viral infection, they get a long cough, shortness of breath and wheezing, which require the use of inhalers or nebuliser," senior consultant Dr Neetu Jain, who runs a post-Covid care clinic at Pushpawati Singhania Hospital and Research Institute, New Delhi, said.

Dr Arun Garg, chairman, Neurology and Neurosciences, Medanta-The Medicity, Gurugram, said he was noticing a spike in stroke cases among young patients not suffering from known risk factors such as diabetes, hypertension and obesity.

"Similarly, we are seeing more cases of encephalopathy (swelling of the brain) without reason and having a confused state of mind following one or two days of fever. Their MRI scans show no changes. These patients have increased significantly after Covid," he said.

In the absence of medical guidelines to diagnose long Covid, doctors are having to resort to broad, non-specific tests and questionnaires to gauge a patient's 'quality of life'.

Studies have shown that the fatigue experienced in long Covid is similar to that in cancer patients, with a quality of life similar to patients of Parkinson's disease.

"We really do not have any test to diagnose long Covid, even though it is definitely a clinical diagnosis. We diagnose long Covid for people who had at least moderate to severe infection, following which they could never regain the quality of life pre-Covid. Checking for inflammatory markers like C-reactive proteins (CRP) can support the diagnosis," Dr Jain said.

"Other than routine blood tests that measure inflammation, we do antibody tests to look for direct markers. In many of these patients, we are finding rare antibodies which are very new to us and were not there pre-Covid," Dr Garg said.

Inflammation persisting despite recovery from acute Covid infection is thought to lie at the heart of long Covid. However, tests to measure this specific immune response are lacking, even as researchers have been working in this direction worldwide.

One such effort comes from Shiv Nadar University, where a team led by Samanta has developed a fluorescent probe capable of detecting inflammation in brain cells that can arise due to Covid infection.

The probe measures nitric oxide levels in brain cells, especially in human microglia cells, where increased NO levels are linked to the SARS-CoV-2 infection. Microglia are immune cells in the brain that fight disease and help maintain brain health.

Lysosomes within microglia, which help clear foreign disease-causing agents like the SARS-CoV-2 virus, produce nitric oxide as part of an immune response to infection. The probe detects nitric oxide produced in lysosomes in response to infection and thereby allows for a measurement of inflammation levels.

This examination method can provide "qualitative information on infection status", said Samanta, corresponding author on the study published in the journal Analytical Chemistry in American Chemical Society.

He explained that patients with pre-existing conditions such as Alzheimer's disease, Parkinson's disease or multiple sclerosis (an autoimmune disorder) could exhibit prolonged neuroinflammation and loss of brain cells following Covid infection.

While the probe has shown efficacy in cell cultures, animal studies would need to be done, before testing it in humans, Samanta said.

Looking at the World Health Organization International Clinical Trials Registry Platform, the study by Harvard Medical School had found that 587 clinical studies were conducted on long Covid, of which about 53 per cent (312) were testing potential treatments.

Most of these were found to be conducted in the US (58), followed by India (55) and Spain (20). The trials looked at interventions including physical exercise, psychotherapy, and pharmacological ones such as paxlovid and fluvoxamine.

However, "to date, only 11 of these 312 studies have published their results that were not confirmative," the researchers wrote.

The team called for studies to look into sleep disorders which were rarely included in the registered clinical studies. Further, interventions targeting the biological processes responsible for long Covid are needed but currently lacking, they said.