A new study in the International Journal of Infectious Diseases should end any lingering idea that SARS-CoV-2 is ‘just another cold virus.’ It shows that a single, relatively short Omicron wave left a long, measurable scar on the adaptive immune systems of tens of thousands of adults and that people with cardiovascular disease (CVD) may be living with something close to chronic immune compromise nearly two years later¹.

This isn’t about individual anecdotes, or small clinic cohorts. It’s a population-scale signal, drawn from more than 40,000 patients in a region of China that had almost no SARS-CoV-2 circulation until late 2022. It is, in many ways, the cleanest before and after picture we have of what one mass SARS-CoV-2 exposure does to human immunity.

The findings demand that we rethink what it means to ‘move on’ from COVID-19, especially if prevailing government strategy relies on repeated, unmitigated reinfections. 

A Natural Experiment: What Happens When a Naïve Population Meets COVID-19?

China’s dynamic zero-COVID policy created an unusual situation. For nearly three years, Shandong Province and its capital Jinan saw very limited SARS-CoV-2 circulation; cases were aggressively isolated, and community spread was largely prevented.

That changed abruptly with the Omicron BA.5.2/BF.7 wave in December 2022 to February 2023. In a matter of weeks, the virus swept through the population. After that wave, community transmission again fell to low levels¹.

Researchers at three major hospitals in Jinan used this sequence of events to ask a stark question:

‘How did a single, intense SARS-CoV-2 wave change the lymphocyte profiles of the people who passed through our hospitals and did their immune systems ever return to baseline?’

They analysed lymphocyte subsets (the major workhorse cells of the adaptive immune system) in 40,537 people who had flow-cytometry testing between January 2021 and August 2024. They divided the data into three non-overlapping cohorts:

• Pre-COVID: Jan 2021 to Nov 2022: essentially no community SARS-CoV-2 circulation
• Mass infection: Dec 2022 to Feb 2023: Omicron wave
• Post-COVID: Mar 2023 to Aug 2024: aftermath, with low ongoing transmission

They excluded ICU patients, people with cancers, transplants, and other conditions that heavily distort immunity. This is important: the signal they describe emerges even after they removed those with the most extreme immune disruption.

They then asked three things:

1. How did key lymphocyte subsets change during the wave?
2. How far did they recover in the 18 to 20 months afterwards?
3. Did certain groups assessed by age, sex, or comorbidity fare worse?

They Found A Lymphocyte Scar

1. Acute phase: a familiar, but widespread, lymphocyte crash

During the mass infection period, there was a marked drop in the absolute counts of:

• CD4+ T helper cells
• CD8+ cytotoxic T cells
• Total CD3+ T cells
• B cells
• Natural killer (NK) cells

At the same time, the percentages of B cells and NK cells, and the CD4/CD8 ratio, went up. That might sound paradoxical until you realise what’s happening: T cells are being depleted more than other subsets, so the proportional balance shifts even when everything is falling.

The fraction of patients with values below the normal range increased sharply across all major lymphocyte subsets. This confirms and extends earlier work in hospital cohorts showing that acute COVID-19 is strongly associated with lymphopenia and altered T, B, and NK distributions².

So far, this is familiar: acute COVID-19 knocks down lymphocytes, and the severity of that drop tracks with acute outcomes³.

2. Twenty months later: recovery but not to baseline

From March 2023 to August 2024, one would expect the population’s immune profiles to return to their pre-COVID baseline if SARS-CoV-2 were simply a transient insult.

They don’t.

Even by August 2024, roughly 20 months after the Omicron wave, median counts remained:

• CD8+ T cells ~9.9% below baseline
• Total T cells ~5.2% below baseline
• CD4+ T cells ~4.4% below baseline

Across the entire post-COVID period, there was a significantly higher proportion of patients exhibiting subnormal T, CD4, CD8, NK and B cell counts compared with before the pandemic¹.

There is partial recovery compared to the acute phase, but the system never fully resets. Importantly:

• The deficit is worse in men than women.
• It is more pronounced in middle-aged and older adults (41–80 years).

These are exactly the groups already at higher risk of severe COVID-19 and Long Covid.

3. The cardiovascular disease subgroup: dramatic, persistent immune collapse

The most alarming signal appears in people with pre-existing cardiovascular disease (CVD).

In this subgroup, the authors first see what looks like recovery in the months after the wave. But from August 2023 onward, they document a sharp, sustained collapse in T-cell and NK-cell counts:

By August 2024, relative to pre-COVID baseline, median values in CVD patients are down by:

• Total T cells: -72.9%
• CD4+ T cells: -74.1%
• CD8+ T cells: -68.6%
• NK cells: -46.3%

This is not a subtle shift. It is a population-level, chronic immune deficit in a group that already faces elevated risk of heart attack, stroke, heart failure, and sudden death.

We already know from large epidemiological studies that COVID-19 survivors, especially those with pre-existing CVD, carry a long-term excess burden of cardiovascular events for years after infection⁴.

Jiang and colleagues provide a plausible hypothesis for those findings: T-cell and NK-cell compartments in CVD patients are not merely ‘slower to recover.’ They appear to be in a state of chronic, severe depletion.

The authors describe this as a biphasic pattern; early partial normalisation followed by abrupt decline consistent with the idea of immune exhaustion under chronic stimulation or stress.

How This Fits With The Emerging Long Covid Literature

Jiang et al.’s findings do not sit in isolation. While the study’s results applied to the general population, they connect directly with a growing body of work describing persistent adaptive-immune changes in people with Long Covid, a cohort that has been subject to more immunological research than the general population.

• A 2023 Nature paper found that people with Long Covid showed reduced central memory CD4+ T cells, increased exhausted T cells, and sustained inflammatory T-cell responses, alongside altered B-cell profiles⁵.
• A 2024 review in Cell summarised evidence that Long Covid is characterised by T-cell dysregulation, immune activation, and uncoordinated adaptive responses, in some cases months to years after infection⁶.
• A 2025 study in Frontiers in Immunology identified a distinct immune signature in Long Covid, featuring reduced CD4, CD8, regulatory T cells, and switched memory B cells, and T-cell populations with low proliferative capacity and diminished activation markers⁷.
• Other cohorts have described persistent lymphopenia and skewed T-cell subsets in a subset of convalescent patients 50 days or more after moderate or severe COVID-19, supporting the idea that normalisation is incomplete in a fraction of survivors⁸.

Taken together, these studies show that chronic mis-wiring of the adaptive immune system is a recurring feature of post-COVID biology in the general population, and particularly impacts those with lasting symptoms, and now, on Jiang’s data, high-risk comorbid groups even at the population level.

Why This Matters: What Does A Chronically Depleted Immune System Mean?

A persistent 5 to 10% reduction in key T-cell subsets at a population level may sound modest. But T-cell homeostasis is finely tuned. Even small chronic shifts can:

• Reduce the margin of safety against new infections
• Impair control of latent pathogens such as EBV, CMV, and VZV
• Alter surveillance against emerging cancers
• Shift the balance of tolerance and autoimmunity

Without evidence of recovery at some point in time, at the individual level, a 70% reduction in T-cell counts in CVD patients is a different story altogether. That pattern starts to look more like a chronic immunodeficient state.

Layer on top:

• Evidence of SARS-CoV-2 persistence in tissues and ongoing antigen exposure in some people months to years after acute infection⁶.
• Evidence for autoantibody production and B-cell dysregulation in both acute and Long Covid⁹.
• Cohort data showing increased long-term risk of cardiovascular, neurological, metabolic, and renal disease after COVID across the severity spectrum¹⁰.

The picture that emerges is not of a virus we ‘get and get over’, but of a pathogen that re-writes immune set-points and organ-system risk profiles for years.

Reinfection Is Not Benign

Crucially, Jiang et al. studied the aftermath of a single major wave in a previously largely unexposed population. Most countries are not in that position.

In many settings, people have now had:

• Two, three, or more documented SARS-CoV-2 infections,
• Plus unrecorded infections,
• Plus ongoing exposure to new variants.

Previous work by Al-Aly and colleagues has shown that reinfections are associated with incremental increases in the risk of death, hospitalisation, and multi-organ sequelae, even after adjusting for baseline health¹¹.

If one wave can shift population T-cell levels for 20 months, the logical question is:

What do three or four waves do over a decade?

We do not yet have that answer. But the precautionary implication is obvious: treating reinfection as inconsequential is a gamble with the long-term integrity of the immune system, both individually and collectively.

Implications For Public Health: What Needs To Change?

Jiang and colleagues conclude, carefully but clearly, that their findings ‘redefine SARS-CoV-2 infection as a condition of long-lasting immune compromise’ and highlight lymphocyte dysregulation as a key immunological feature of Long Covid, particularly in people with cardiovascular disease¹.

If we take that seriously, several policy implications follow.

1. Stop pretending COVID is over

SARS-CoV-2 has not gone away and it has not become harmless just because it is widely and regularly circulating. Given the data:

• Minimising infections and reinfections remains a rational public health goal.
• This is not only about preventing deaths now but about preserving immune and vascular health over the next 10 to 20 years.

2. Air quality is immunology

If repeated infection carries a cumulative immune cost, then reducing viral exposure is not a lifestyle preference; it is an immune-preservation strategy.

That means:

• Treating indoor air quality (ventilation, filtration, CO₂ monitoring) as critical infrastructure, not optional extras
• Normalising high-filtration masks (FFP2/N95) especially in high-risk indoor settings (healthcare, care homes, crowded transport), and high-risk groups
• Building layered protection into schools, workplaces, and public venues to reduce transmission of all respiratory pathogens, not just SARS-CoV-2

3. Prioritise high-risk groups for monitoring and protection

The extreme T-cell depletion seen in CVD patients demands targeted responses:

• Immune monitoring (including lymphocyte subsets) could become part of long-term follow-up for CVD patients post-COVID.
• Clinicians should keep a high index of suspicion for:
  • recurrent infections,
  • atypical infections,
  • sudden deterioration in vascular status.
• Policy makers should treat CVD patients, older adults, and other high-risk groups as priority populations for:
  • updated vaccination,
  • antiviral access,
  • exposure reduction measures in healthcare and social care settings.

4. Invest in Long Covid and infection-associated chronic illness research

Jiang et al.’s study is ecological and cross-sectional; it shows strong associations but cannot track individuals over time. The next steps are:

• Large, longitudinal cohorts with serial immune profiling before and after reinfections. It is essential to know whether the immunological impacts of SARS-CoV-2 are cumulative.
• Studies linking immune signatures to concrete clinical outcomes (infections, cancers, cardiovascular events, neurocognitive decline)
• Trials of therapies aimed at immune repair and viral persistence, not just symptom management

These efforts should not be siloed; SARS-CoV-2 is now one of several pathogens linked to infection-associated chronic conditions. Understanding this broader category will be crucial for future preparedness.

5. Communicate honestly with the public

Finally, the messaging needs to catch up with what the evidence is now clearly telling us. People have been misinformed, repeatedly, that:

• “COVID-19 is mild”
• “Reinfections are unavoidable and largely harmless”
• “COVID-19 is now akin to seasonal flu”

The immune data do not support that reassurance.

Honest communication would say:

• Acute risk has been reduced by vaccination and prior infection, especially for younger, healthier people, but
• Each infection and reinfection carries a non-zero risk of chronic immune and organ-system consequences, and
• Simple, structural measures (clean air, sensible masking, staying home when sick, vaccination, early treatment) can meaningfully reduce those risks.

A New Disease Paradigm

The Jiang study is a landmark because it captures, at population scale, what many smaller studies and clinical observations have been hinting at for years:

SARS-CoV-2 is not just an acute respiratory virus. It is an immune-modifying, vascular-damaging pathogen whose effects can be measured long after the fever and cough have gone. Leading scientists and COVID-19 researchers such as Anthony Leonardi, Akiko Iwasaki, Danny Altmann, Michael J Peluso, Amy Proal, Ziyad Al-Aly and many others have cautioned about the long-term impacts of infection, but their concerns have been minimised by the same people who are now cancelling vaccine programs for children, supported by scientists who chose expediency over evidence. The evidence is now clear and growing.

In a world where nearly everyone has been infected at least once, and many people have now had it multiple times, that matters. It means that the state of our immune systems in 2035 and 2045 is very likely to be, in part, a function of how seriously we took this virus in the 2020s.

We cannot undo the past waves. But we can choose whether the next decade is defined by accumulated, preventable damage, or by deliberate efforts to protect the immune health of populations already living with the legacy of mass infection.

For information on how to reduce your risk of infection, click here.

GLOSSARY OF KEY TERMS 

Adaptive Immune System

The part of the immune system that learns from infections. It uses specialised cells to target specific viruses or bacteria and remembers them for faster protection in the future.

Lymphocytes

A family of white blood cells that run the adaptive immune system. The main types are T cells, B cells, and NK cells.

T Cells and Their Subtypes

• T Cells (CD3+ T cells)
  A major class of immune cells that coordinate and carry out targeted immune responses. They identify and kill infected or abnormal cells.
• CD4+ T Cells (T Helper Cells)
  These cells act as the “commanders” of the immune system. They direct other immune cells, help B cells make antibodies, and regulate inflammation.
• CD8+ T Cells (Cytotoxic T Cells)
  These are the ‘assassins’ of the immune system. They directly kill virus-infected cells, cancer cells, and cells behaving abnormally.
• CD4/CD8 Ratio
  A measure of balance between helper (CD4) and killer (CD8) T cells. A shift in this ratio can signal immune stress or dysregulation.

Other Key Immune Cells

• B Cells
  White blood cells that make antibodies, the proteins that recognise and neutralise viruses and bacteria. B cells also form ‘memory’ cells to protect against reinfection.
• Antibodies
  Proteins made by B cells that attach to viruses or bacteria and help the immune system destroy them.
• NK Cells (Natural Killer Cells)
  Immune cells that act fast to kill infected or cancerous cells, even without prior exposure. They form part of the body's rapid-response defence.

Immune Function Terms

• Lymphopenia
  Lower-than-normal numbers of lymphocytes.This can indicate immune suppression, ongoing infection, or immune system stress.
• Immune Exhaustion
  A condition where immune cells, especially T cells, stop working properly due to repeated or chronic stimulation, as seen in chronic infections. Exhausted cells react slowly and may fail to control viruses.
• Immune Dysregulation
  When the immune system behaves abnormally, either underreacting, overreacting, or coordinating poorly.
• Immune Compromise / Immunocompromised
  A weakened immune state where the body is less able to fight infections or control abnormal cell growth.

Latent Viruses Mentioned in the Article

These viruses infect people early in life, then stay dormant in the body. A healthy immune system keeps them under control, but they can reactivate if immunity weakens.

• EBV (Epstein–Barr Virus)
  A very common virus that causes glandular fever / ‘mono.’ After the initial infection, it becomes dormant in the body. Reactivation has been linked to fatigue, immune dysfunction, and, rarely, certain cancers.
• CMV (Cytomegalovirus)
  A widespread virus that most people acquire silently. Like EBV, it remains in the body for life. Reactivation can stress the immune system and is more dangerous in immunocompromised people.
• VZV (Varicella-Zoster Virus)
  The virus that causes chickenpox. After recovery, it hides in nerve cells. If immunity wanes, it can reactivate later in life as shingles.

Other Technical Terms

• Flow Cytometry
  A laboratory technique that uses lasers to count and characterise immune cells in a blood sample. This is how T-cell, B-cell, and NK-cell levels were measured in the study.
• Comorbidity
  A long-term health condition someone already has, such as cardiovascular disease, diabetes, or chronic lung disease.
• Cardiovascular Disease (CVD)
  Any disease of the heart or blood vessels, for example, coronary artery disease, stroke, heart failure, or arrhythmia.

Reinfection

Becoming infected again with the same pathogen, in this case SARS-CoV-2, often with a different variant.