What makes long Covid long: New evidence raises concern and diagnostic hope

Research finds persistent immune and clotting abnormalities, underscoring the scale of India's long Covid burden and its impact on heart and vascular health

More than five years after the first wave, Covid-19 continues to cast its shadow over India’s health landscape. A new study published in the Journal of Medical Virology (October 2025) has added renewed urgency to the need to tackle a subject clinicians have been flagging over the years: Persistent blood abnormalities in long Covid patients that may be causing chronic fatigue, cognitive problems, and cardiovascular symptoms. 

The study — led by researchers from France and South Africa — found that long Covid patients showed lasting changes in their ‘complement system’ — a group of 20 proteins that are integral to natural immunity. 

The markers of ‘complement activation’ remained elevated long after the infection itself had abated, reinforcing the theory that chronic immune activation and tiny, hard-to-detect blood clots are central to long Covid’s persistence.

 

Although the findings don’t prove that these clots cause long Covid, they strengthen the theory that persistent immune and vascular dysfunction play an important role. 

For India, the implications are significant — around 45 million Covid infections have been officially reported since 2020. But actual numbers may be far higher because of unreported incidence of a single person contracting Covid multiple times. 

A study led by Banaras Hindu University (BHU) researchers published in the International Journal of Infectious Diseases in 2023 estimated that the actual coronavirus cases in the country may have been between 580 to 980 million. The research has shown that “the actual corona infection in India was at least 17 times higher," according to a statement by BHU last year. This could be due to the overwhelming number of asymptomatic people, which was several-fold higher than those who showed symptoms — the basis for the official count. 

The Indian Council of Medical Research’s fourth national serosurvey in mid-2021 showed 67.6 per cent seroprevalence, suggesting that actual virus exposure would have exceeded 900 million by that point alone. With subsequent waves, experts estimate that virtually the entire adult population of India has been infected at least once, and many twice or thrice. 

Even by conservative assumptions that 5-10 per cent of infected individuals develop long Covid, India today may be home to 50-100 million infected individuals — many silently coping with breathlessness, fatigue, palpitations, brain fog, or unexplained clotting tendencies. 

Against this backdrop, the new study’s findings, which strengthen biological explanations for long Covid, are particularly relevant to clinicians across the country who often struggle to diagnose the condition in the absence of definitive tests. 

The Journal of Medical Virology paper focuses on the complement system. In long Covid patients, researchers found persistent elevation of complement fragments (the proteins), signs of blood vessel stress, evidence of ongoing microclot formation, and altered inflammatory pathways. 

What distinguishes this study is its detailed immune profiling and its conclusion that long Covid is not merely psychosomatic or a residual-post viral syndrome but a measurable biological state involving immune dysregulation. 

For India’s medical community, where long Covid is often underdiagnosed or mislabelled as stress or anxiety, these findings offer a clearer path.

 

“Recent research has indeed highlighted unusual or persistent changes in the blood of individuals with long Covid, and these findings are extremely significant,” said Dr Manisha Arora, director, internal medicine, C K Birla Hospital, Delhi. 

“We have observed several blood-related abnormalities after Covid-19, most notably a higher incidence of thrombosis — pulmonary embolism, deep vein thrombosis, myocardial infarction due to coronary thrombosis, and even cerebral venous sinus thrombosis.” 

In rare cases, she has seen clotting in major intra-abdominal arteries, “which was previously uncommon but is now being increasingly reported”. 

This aligns closely with the study’s central message: The immune system of long Covid patients does not return to baseline, and persistent inflammation continues to damage healthy cells and blood vessels. 

A silent burden 

India’s Covid survivors are a heterogeneous group: Elderly individuals, young adults infected multiple times, those with comorbidities, and others who were just asymptomatic. As post-pandemic clinic patterns emerge, vascular and cardiac complaints continue to be a steady trend. 

“Yes, we have seen a clear rise in vascular and circulation-related complications after Covid-19,” Arora noted. “Pulmonary embolism, deep vein thrombosis, myocardial infarction and cerebral venous sinus thrombosis were especially prominent after major waves.” These conditions refer to breathlessness, heart attacks and blockage of veins in the brain. 

This aligns with global epidemiological evidence. The UK Biobank — a ‘bank’ of human samples — tracked 10,005 Covid patients and found they had double the risk of major cardiovascular events over about 1,000 days. Those hospitalised had nearly four times the risk compared with never-infected individuals. 

But Indian cardiologists point to other factors too.

 

“In day-to-day clinical practice, physicians are not observing a dramatic rise in heart attacks solely due to Covid,” said Dr Rushikesh Patil, associate director – cardiology at Dr L H Hiranandani Hospital, Mumbai. He noted that lifestyle factors such as “poor habits, stress, and obesity may act as confounding factors,” even though Covid clearly worsens cardiovascular risk in the acute phase. 

One mechanism he highlights is the formation of neutrophil extracellular traps (NETs) — filament-like structures released by certain white blood cells. These are key parts of the body’s natural immune system but they can trigger clotting in tiny vessels, affecting organs like the lungs and brain. “These NETs are believed to contribute significantly to long Covid symptoms,” he said. 

One theory suggests the formation of tiny blood clots that are too small to cause major events like a stroke or heart attack can still impair the function of organs such as the lungs and brain. 

“Early in the pandemic, studies showed that Covid affected the cardiovascular system in up to 25 per cent of patients, leading to issues such as irregular heartbeats, heart failure, strokes, and heart attacks. Long-term data, however, is still limited,” he added. 

It has also been documented that individuals with blood group O have a lower risk of heart disease than those with A, B, or AB blood types. 

The difficulty lies in disentangling long Covid from India’s already-heavy burden of metabolic and heart disease. For clinicians, understanding the biological signatures becomes essential. 

India aligns 

The Indian experience matches what the global research community is reporting. 

“Many people with long Covid show changes in their blood, including tiny clots, overactive platelets, and stressed blood vessels,” said Dr Deepesh G Aggarwal, consultant physician & HOD - critical care medicine at Saifee Hospital, Mumbai. 

“These small clots make it harder for blood to flow through the smallest vessels, which lowers oxygen supply and leads to symptoms like constant tiredness and brain fog.” 

He said blood tests in symptomatic patients often show elevated markers such as D-dimer, Factor VIII, and von Willebrand Factor (VWF) — indicators of clotting stress. Red blood cells, too, may change shape and flexibility, making physical exertion harder. Low iron levels and inflammation-related anaemia are common, compounding fatigue. 

These insights mirror what the Journal of Medical Virology study finds in European and South African patients — suggesting long Covid may share core biological features across populations. 

Hidden cost 

Epidemiologists broadly estimate 50-100 million Indians suffering from long Covid. Not all long-Covid cases are severe or persistent. But even if 10–20 million individuals face moderate impairment affecting productivity or exercise tolerance, the economic impact is not trivial. 

Unlike Western nations, where long Covid clinics were set up early on in the pandemic, India’s health system — stretched by the periodic surges — has had to integrate long Covid care into general internal-medicine and cardiology care. This risks missing subtle cases. 

“Long Covid often goes unrecognised,” Arora cautioned. “Its symptoms overlap with many other chronic conditions. The absence of objective biomarkers further complicates diagnosis.” 

Aggarwal agrees, emphasising that variations between patients mean doctors rely more on evaluating symptoms and related conditions than standardised testing. 

 

As India continues to struggle with non-communicable diseases — heart disease, diabetes, obesity — the overlapping spectrum of long Covid may further strain primary care systems. 

Even before Covid, India was the heart disease capital of the world, with nearly 2.8 million deaths annually attributed to cardiovascular conditions. 

Post-pandemic, anecdotal evidence of younger heart attack victims made headlines, but cardiologists say the story is more layered. Covid may have accelerated underlying risks for some, but lifestyle factors, genetic predisposition, and delayed care during lockdowns contributed as well. 

Patil noted that while acute Covid clearly increases heart complications, the longer-term impact is modest when compared with lifestyle-driven disease. 

However, when even a small percentage of a billion-plus population faces increased clotting risks or cardiovascular stress, the absolute numbers remain high. 

The new research does not answer all questions, but it shifts the discourse from “Is long Covid real?” to “How do we test, monitor, and treat it?” 

As India confronts the legacy of a pandemic that touched almost every home, recognising long Covid as a biological condition — not merely as subjective symptoms — could shape future policy, health budgets, insurance coverage, and workplace practices.