Persistent Virus in Long Covid:
The Emerging Science

Understanding the concept of a persistent virus in Long Covid

Long Covid, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), describes symptoms such as fatigue, breathlessness and brain fog that persist for months after the initial infection has cleared.

Among several hypotheses proposed to explain this, one has become increasingly compelling: the Persistent Virus Hypothesis. It suggests that remnants of SARS-CoV-2, viral RNA, proteins, or even small populations of active virus, may persist in body tissues. These residual viral elements can continue to stimulate the immune system, causing chronic inflammation and ongoing symptoms.

Research groups at institutions such as Harvard Medical School, Mayo Clinic, Stanford University, Yale School of Medicine, King’s College London, and the NIH RECOVER Initiative are all investigating this possibility.

This page summarises what is currently known, explores Attomarker’s findings on immune endotypes, and explains how this understanding may one day help to personalise treatment for people with persistent symptoms.

Evidence for viral persistence in Long Covid

The science is evolving, but growing data support the probability that SARS-CoV-2 may not always be completely eliminated after acute infection.

Findings across multiple studies include:

Although not yet definitive proof, these studies together indicate that persistent viral material, and the immune system’s continued response to it, may explain many of the chronic effects seen in persistent virus Long Covid.

Persistent virus – now a probability, not a possibility

The evidence that SARS-CoV-2 can persist in the human body for months after acute infection has grown steadily. What began as an intriguing hypothesis is now considered a probable and significant contributor to Long Covid pathophysiology.

More than a dozen peer-reviewed studies have demonstrated the presence of viral RNA, proteins or antigens in tissues long after patients test negative on conventional PCR tests. Together they confirm that the virus can linger in multiple organs and systems.

However, the field remains emergent.
While persistence itself is now widely accepted, the mechanisms by which residual viral material drives the diverse symptom patterns of Long Covid are less clearly mapped. Some patients may experience direct tissue effects from ongoing viral replication, while others appear to have immune dysregulation, endothelial damage or autoimmune responses triggered by lingering antigens rather than live virus.

Researchers agree on three key points:

Where and how the virus might persist

The virus appears capable of surviving in areas of the body with lower immune surveillance, where it can remain unnoticed yet continue to provoke an immune response.

Evidence of persistence has been found in:

These reservoirs could act as chronic sources of immune activation even after acute infection has resolved.

Comprehensive list: where SARS-CoV-2 has been shown to persist

Below is a structured list of organ systems and tissue sites with evidence of viral persistence or antigen detection, supported by published studies.

Areas SARS-CoV-2 has Been Found to Linger

Immune endotypes: new insight into why some people remain unwell

Attomarker’s multiplex antibody research has shown that Long Covid may be associated not only with viral persistence but also with distinct immune-response patterns, called endotypes.

An immune endotype describes how a person’s immune system has responded to infection or vaccination, reflected in the quantity and quality of antibodies across multiple SARS-CoV-2 variants.

Through analysis of hundreds of samples, Attomarker’s studies have found that about 60 to 65 percent of people with Long Covid show an immune endotype characterised by either insufficient antibody levels or low-quality (poorly binding) antibodies to one or more variants.

Why immune gaps might explain persistent symptoms

If immunity is incomplete, residual viral particles may survive in protected tissues. This allows the virus or its antigens to remain active and provoke inflammation over time.

Possible sequence:

An over-reactive or hyper-immune endotype may instead cause excessive antibody activity and self-reactivity, leading to autoimmune-like symptoms even when no virus remains.

Towards personalised approaches: filling the immune gaps

Attomarker is collaborating with research partners to study how these immune gaps might be addressed through personalised immunological strategies. The goal is to strengthen gaps identified in an individual’s antibody spectrum with interventions tailored to that pattern.

Approaches under exploration include:

Ongoing research and clinical trials

Research into persistent virus Long Covid is expanding globally. Several large programmes are underway to understand viral reservoirs, immune dysregulation and therapeutic options.

Therapeutic implications of the persistent virus hypothesis

Understanding the biological mechanisms of persistence is guiding early studies of new interventions.

Current areas of exploration:

A balanced view of the science

The persistent virus hypothesis is one of several explanations for Long Covid. Other mechanisms under investigation include autoimmunity, reactivation of latent viruses such as Epstein–Barr virus, and metabolic or mitochondrial dysfunction.

It is increasingly clear that multiple mechanisms interact, and different individuals may have different biological drivers.

By identifying immune endotypes and mapping antibody spectra, researchers aim to connect these mechanisms, linking viral persistence, immune dysfunction and symptom pattern into a coherent scientific model.