Healthcare

Long COVID: toward an acceleration of Alzheimer’s disease?

Published on 04 May 2026 Read 25 min

long covid alzheimer agency consulting consultancy experts

The World Health Organization (WHO) currently reports nearly 780 million cases of COVID-19, with a mortality rate of 1%. Long overlooked, patients with Long COVID are estimated to represent 6% to 10% of the global population infected with COVID-19. Today, emerging evidence suggests a link between Long COVID and an acceleration in the development of Alzheimer’s disease¹². While the Alzheimer Europe consortium (Alzheimer Europe) projects a 58% increase in Alzheimer’s cases by 2050, this figure may be underestimated. Could we be on the brink of a new public health crisis driven by the resurgence of Alzheimer’s cases? Will we be able to effectively counter this accelerated brain aging?

In this article, Alcimed explores the relationship between Long COVID and Alzheimer’s disease to identify the challenges the pharmaceutical industry must address.

Long COVID: a range of symptoms increasingly recognized by experts

Initially disputed by physicians and researchers, the concept of Long COVID emerged from patients as early as 2020. That same year, the World Health Organization (WHO) defined Long COVID as a range of symptoms (fatigue, dyspnea, etc.) occurring within three months following a COVID-19 infection and lasting for at least two months¹. Today, Long COVID is better recognized by experts and health authorities, thanks to scientific advances and the mobilization of patient associations.
As a result, nearly 45,000 studies now reference the term Long COVID. However, its origin remains unclear, although the existence of a viral reservoir or chronic inflammation is suspected.

Long COVID and the acceleration of Alzheimer’s disease development

As early as 2020, neurological and molecular observations suggested an accelerated progression of Alzheimer’s disease in patients with severe or prolonged forms of COVID-19²³.

Cognitive impairments characteristic of Alzheimer’s disease

Neuropsychological tests conducted after COVID-19 infection reveal cognitive impairments similar to those observed in Alzheimer’s disease (attention, memory, language, depression)⁴⁵. Cognitive improvement has been observed over the course of COVID-19, but it remains difficult to quantify due to heterogeneity in assessments, patient neurological follow-up, inclusion of control groups, and other factors⁶⁷⁸. These impairments persist from several months to several years in 25% of Long COVID patients⁹¹⁰. Among patients already affected by dementia, COVID-19 increases the risk of mortality fivefold.

Chronic inflammation exacerbates Alzheimer’s disease development

Neuroinflammation is one of the key mechanisms underlying Alzheimer’s disease, which is characterized by deposits of amyloid-beta (Aβ) plaques and Tau proteins. Other processes, such as oxidative stress and disruption of the blood–brain barrier (BBB), also contribute to this interconnected pathological dynamic¹¹¹²¹³.

Studies reveal similar mechanisms between brain damage caused by SARS-CoV-2 and those involved in Alzheimer’s disease. Viral infection initially triggers a cytokine storm, leading to systemic inflammation that compromises the integrity of the blood–brain barrier. The nervous system is then exposed to peripheral inflammation and the virus, fostering a neuroinflammatory environment and oxidative stress conducive to the accumulation of Aβ plaques and Tau proteins. Over time, these processes may amplify and accelerate the neurodegenerative cascade, particularly in Long COVID patients¹⁴.

Aggravating genetic factors

By analyzing 250 studies, 46 genes have been identified as potentially influencing both SARS-CoV-2 infection and the development of Alzheimer’s disease. These genes are involved in brain function and immuno-inflammatory responses. Among them, the apolipoprotein E ε4 (APOE4) gene and HLA-DRB1*04:01 have been identified¹⁵.

Although still debated, APOE4 is believed to increase neuroinflammation, disrupt brain development, raise the risk of Alzheimer’s disease fourteenfold, and double the risk of COVID-19. APOE4 is expressed in approximately 30% of Long COVID patients with cognitive impairment, compared with 16% in those without cognitive decline.

HLA-DRB1*04:01 is a class II major histocompatibility complex responsible for presenting antigens on the cell surface and initiating an adaptive immune response. It may worsen COVID-19 outcomes while providing protection against Alzheimer’s disease by presenting a form of Tau prone to aggregation.

These associations highlight the importance of elucidating interactions between genes, infection, and Alzheimer’s disease to design new therapies.

Long COVID and Alzheimer’s disease: new challenges for the pharmaceutical industry

Challenge 1: develop robust diagnostic and predictive tools for Long COVID

Unlike Alzheimer’s disease, there are currently no reliable diagnostic tools for Long COVID. According to the French National Authority for Health (Haute Autorité de Santé, HAS), Long COVID diagnosis is based on clinical evaluation (both physical and psychological) and the exclusion of other potential causes, such as heart failure. The complexity of diagnosis lies in the absence of specific biomarkers and the diversity of patient manifestations. In clinical study protocols, inclusion criteria—such as neurological testing and prior COVID-19 history—vary across cohorts, making it difficult to establish a clear link with Alzheimer’s disease¹⁶[/mfn].

Diagnosis could rely on high-resolution imaging and the use of vascular, neuroendocrine, or oxidative stress biomarkers. Today, these tools make it possible to assess inflammation levels or organ damage (e.g., lungs)¹⁷. By further correlating them with patient clinical progression, and combining them with genetic analysis—still underutilized—it may become possible to predict the long-term trajectory of Long COVID, particularly the risk of developing cognitive disorders and accelerating Alzheimer’s disease progression¹⁸.

Read also: The Road to AI Adoption in Medical Imaging: Deployment Pathways & Hurdles

Developing Long COVID-specific diagnostics will enable a better understanding of its link with Alzheimer’s disease and support the deployment of innovative therapies to ensure appropriate patient management and slow neurodegeneration.

Challenge 2: develop therapeutic targets for Long COVID

Currently, Long COVID treatment is primarily symptomatic, based on physical rehabilitation, with anti-inflammatory drugs playing a secondary role. However, the synergy between SARS-CoV-2 infection, an excessive immune response, and genetic predispositions exacerbates neuroinflammation, thereby accelerating progression toward Alzheimer’s disease¹⁹.

Naturally, therapies under development incorporate an immunomodulatory component, particularly through anti-inflammatory drugs (colchicine, methylprednisolone). Nutraceutical approaches, such as ascorbic acid with anti-inflammatory and antioxidant properties, are also being explored²⁰.

The use of small interfering RNA (siRNA) cocktails, some administered via nasal spray, is being studied to prevent and treat COVID-19. Others, currently investigated in Alzheimer’s disease, could benefit Long COVID patients. The hypothesis of a viral reservoir underlying Long COVID could inspire a strategy derived from HIV treatment, known as “Shock and Kill,” aimed at eliminating latent SARS-CoV-2 potentially involved in chronic inflammation.

Deepening our understanding of Long COVID will be essential to develop treatments targeting inflammation that may accelerate Alzheimer’s disease.

In the coming years, Long COVID patients are likely to contribute to an increased number of Alzheimer’s cases. Advancing knowledge and developing innovative therapies will primarily depend on reliable diagnosis, which is essential for early detection and patient management.

Alcimed can support you in exploring these therapeutic areas or identifying the right partner to contribute to tomorrow’s innovations, in the face of what could become the next public health crisis. Feel free to contact our team!

About the authors,

Stacy, Consultant in Alcimed’s Healthcare team in France

Martin, Project Manager in Alcimed’s Healthcare team in France

Have a project and want to discuss it?

To go further

Articles

Alzheimer’s Disease and inflammation: towards a 2-in-1 treatment strategy?

Could the success of Alzheimer's Disease treatment be found with drug repurposing and a 2-in-1 strategy targeting both protein aggregates and neuroinflammation? Our Healthcare team at Alcimed ...
Healthcare

State of the Art on Advances and Challenges in the Management of Patients with Alzheimer’s Disease

Challenge 1: Developing Treatments to Cure or Slow the Progression of Alzheimer’s Disease In France, four medications are available to treat cognitive symptoms in Alzheimer’s patients, but they ...
Healthcare

The 4 key roles of microbiota in the gut-brain axis: focus on Alzheimer’s disease

Gut microbiota influences neurotransmitter synthesis The gut microbiota communicates with the brain through neural pathways, influencing brain activity, emotions, and cognitive ...