Immunotherapies and monoclonal antibodies are increasingly discussed as potential treatments for Long Covid. While early research suggests possible benefits in selected patients, evidence remains limited, and risks must be carefully considered.
Long Covid has forced clinicians to confront an uncomfortable reality. A significant subset of patients do not follow a trajectory of gradual recovery, nor do they fit neatly into existing diagnostic or treatment frameworks.
Instead, they present with persistent, fluctuating, multisystem symptoms that strongly suggest immune dysregulation, yet remain poorly served by conventional symptom-focused management.
Current evidence is growing but remains fragmented, marked by biological plausibility, early signals of benefit in selected cohorts, and substantial uncertainty.
This article reviews what is currently known, what has been trialled, what remains hypothetical, and why immune-targeted therapies may help some people with Long Covid while being ineffective or inappropriate for others.
The Immunological Rationale Behind Long Covid
Multiple lines of research now suggest that Long Covid is not a single entity, but a spectrum of post-viral syndromes with overlapping immune mechanisms.
These include:
- Persistent immune activation
- Autoantibody production
- Impaired immune resolution
- Endothelial dysfunction
- Autonomic instability
Studies have demonstrated abnormalities in T-cell exhaustion profiles, altered B-cell subsets, elevated inflammatory cytokines, and in some patients, the presence of autoantibodies targeting adrenergic and muscarinic receptors.
This has led to the hypothesis that a proportion of Long Covid cases represent an immune-mediated condition triggered by SARS-CoV-2, rather than ongoing tissue damage alone.
Importantly, these immune signatures are not uniform. This heterogeneity is central to understanding why immunotherapies cannot be approached as a single solution.
Monoclonal Antibodies: What Has Been Explored
Monoclonal antibodies entered the Long Covid discussion initially through their use in acute infection.
Early observational reports suggested that some patients experienced partial symptom improvement after receiving anti–SARS-CoV-2 monoclonal antibodies for reinfection. However, these observations were uncontrolled and inconsistent.
More recently, attention has shifted toward monoclonal antibodies targeting immune pathways rather than the virus itself.
B-cell depleting therapies such as rituximab have attracted interest due to parallels with autoimmune and post-infectious conditions. Small case series suggest potential benefit in highly selected patients, but controlled trial data in Long Covid remain extremely limited.
Cytokine-targeting agents have also been proposed, but current evidence is insufficient to support routine use outside research settings.
Intravenous Immunoglobulin and Immune Modulation
Intravenous immunoglobulin (IVIG) has been considered due to its role in immune-mediated neuropathies and dysautonomia.
Case reports describe improvement in selected patients with:
- Small fibre neuropathy
- Autonomic dysfunction
- Suspected immune-mediated neurological involvement
However, IVIG is resource-intensive, costly, and not without risk.
Evidence remains limited to small cohorts, with no large randomised trials in unselected Long Covid populations.
Why Some Patients Respond and Others Do Not
Long Covid is not a uniform condition.
It includes:
- Inflammatory-dominant phenotypes
- Autoimmune-dominant phenotypes
- Autonomic-dominant phenotypes
- Metabolic or endothelial dysfunction
Patients with clear immune activation or autoimmunity may benefit from immune modulation.
Others may not.
This distinction is critical to avoid both ineffective treatment and harm.
Risks, Costs, and Ethical Considerations
Immunotherapies are not benign.
Risks include:
- Infection
- Infusion reactions
- Thrombotic events
- Immune suppression
Cost is also significant, with some therapies reaching tens of thousands of pounds annually.
In the absence of strong evidence, routine use raises ethical and health economic concerns.
What Clinicians Can Do Now
Clinicians can:
- Recognise immune-mediated patterns
- Screen for autoimmune overlap
- Identify autonomic dysfunction
- Validate post-exertional symptom exacerbation
Avoiding harm is equally important. Overexertion and inappropriate rehabilitation strategies may worsen outcomes.
Research Directions and What Remains Unknown
Ongoing research is exploring:
- Immune phenotyping
- Antiviral persistence
- Immune reset strategies
- Targeted modulation
Key unanswered questions include:
- Are immune changes drivers or consequences?
- Can immune modulation restore regulation?
- How can responders be identified safely?
Conclusion
Immunotherapies and monoclonal antibodies represent a biologically plausible but unproven approach for selected cases of Long Covid.
Current evidence supports caution, careful patient selection, and continued research rather than routine use.
Long Covid challenges medicine not because it lacks treatments, but because it requires a more nuanced understanding of immune dysfunction and recovery.
FAQs
Do immunotherapies help Long Covid?
In some cases, particularly where immune dysfunction is present, they may help, but evidence is still limited.
Can immunotherapy cure Long Covid?
No immunotherapy has been shown to cure Long Covid. Some patients with specific immune or autoimmune features may experience improvement, but responses are variable and often incomplete.
Who is most likely to benefit from immunotherapy in Long Covid?
Current evidence suggests that only a subset of patients may benefit, particularly those with clear signs of immune dysregulation, autoimmunity, or inflammatory activity. There is no widely accepted biomarker to guide selection.
Are these treatments safe?
They carry risks including infection, infusion reactions, and immune suppression, and should only be used under specialist supervision.
Are immunotherapies available through the NHS for Long Covid?
In most cases, no. Access is usually limited to clinical trials or highly selected cases managed by specialists.
How much do immunotherapies for Long Covid cost?
Costs can range from thousands to tens of thousands of pounds per year. Most treatments are not routinely funded without clear indications.
Is rituximab used for Long Covid?
It has been explored in small studies but is not routinely recommended.
Can IVIG improve Long Covid symptoms?
Some patients with autoimmune and neurological involvement report improvement, but evidence remains limited.
Are drugs like Pemgarda, Evusheld, or Sipavibart used for Long Covid?
These monoclonal antibodies were developed for COVID-19 prevention or treatment. Their role in Long Covid is not established yet, and they are not routinely used outside research.
In the United States, some private consultants may offer treatments such as Pemgarda in selected patients. Clinical trials are ongoing, including Sipavibart research led by Dr Klimas, but results are still emerging.
In Europe, Evusheld and more recently Sipavibart may be accessed privately in some settings. However, these approaches vary widely, and patient-reported outcomes are mixed and very expensive.
Could viral persistence explain why monoclonal antibodies might help?
One hypothesis is that persistent viral fragments continue to stimulate the immune system. Monoclonal antibodies may reduce this in some cases, but this remains unproven.
Disclaimer
This article is for educational and informational purposes only. It does not constitute medical advice and should not replace individual clinical judgement or specialist consultation.