Lidocaine Treatment for Long COVID — What You Need to Know

For Long Covid, it is estimated that approximately 450 million people worldwide suffer from chronic, non-spontaneously improving symptoms. In the Netherlands, this concerns an estimated 350,000–400,000 people (about 2–2.5% of the population) with long-term symptoms, of whom around 100,000 are seriously ill.

Many of these seriously ill patients fall (partially) off the radar because no reliable diagnostic test is yet available. Medical specialists such as neurologists, cardiologists, and pulmonologists usually find few abnormalities in blood tests or imaging that could explain the severity of the symptoms. As a result, the condition has long been approached either as a difficult-to-diagnose multisystem disease with various possible underlying mechanisms, or – incorrectly – interpreted primarily as psychosomatic, with major medical, social, and financial consequences for patients.

The growing understanding that long COVID likely has a significant immunological component and appears treatable in at least a subset of patients is expected to usher in a new phase for both patients and healthcare providers. The therapy described here is specifically aimed at people with severe, debilitating symptoms; this is a very large group, in the Netherlands and worldwide, for whom hardly any effective treatment options are currently available.

In the study, we describe the results up to and including 36 weeks after the start of treatment, but in practice, the duration of treatment varies per patient. Patients are typically treated for several months; treatment is continued until the patient has stably recovered to approximately 80% of pre-onset disease functioning. At that point, tapering off and, where possible, discontinuation are started in consultation between the patient and the treating physician.

The treatment consists of subcutaneous injections of lidocaine-HP-β-CD, which patients administer themselves at home according to a fixed schedule. During the treatment, they are intensively monitored: patients report the severity of their symptoms daily via a web application, complete more extensive questionnaires at fixed intervals, and attend a clinical check-up approximately every six weeks. This allows the course of symptoms, the timing of tapering, and the safety of the treatment to be closely monitored.

The skin reactions that may occur with daily subcutaneous injections are classified as "mild side effects" in the article because they do not cause permanent damage. In clinical research, side effects are classified according to severity: mild, moderate, or severe (severity grading). Skin reactions such as redness, swelling, bruising, or hardening fall into the category of mild adverse events.

This does not mean that these symptoms cannot be bothersome for patients. However, many patients did not find the skin reactions resulting from the daily injections bothersome in proportion to the perceived improvement in their symptoms. The skin problems usually disappear within a few weeks to months after tapering off or stopping the injections.

Skin reactions are to be expected with frequent subcutaneous injections, as is also known with, for example, insulin or anticoagulant treatments. However, these reactions do require attention. Over time, various strategies have been implemented to support the skin as effectively as possible and minimize problems, such as cooling, massage, lymphatic drainage, the use of grid dressings, and regularly rotating injection sites.

There is indeed follow-up after stopping or tapering off treatment. The published results run until April 2025; we have continued following these patients since then. We are currently preparing a follow-up publication with data up to 66 weeks. Preliminary analyses show that the positive effects on both physical and mental health remain stable in many cases or even increase further, and that a significant proportion of patients have been able to taper off or completely stop the medication without a relapse to their previous level of symptoms.

At the same time, precisely because of the impact of these findings, we consider it important to confirm and refine the results in a formal, placebo-controlled Randomized Controlled Trial. Such an RCT is currently being prepared.

This question is understandable. The pharmacy preparation of lidocaine with HP-β-cyclodextrin is not (yet) reimbursed by health insurers, causing patients and doctors to look for cheaper alternatives.

However, standard lidocaine infusion fluid is not suitable for this.

In pain medicine, this form of lidocaine is administered exclusively in a hospital setting, under continuous medical supervision. Administration via infusion or injection (intravenous or subcutaneous) can lead to excessively high lidocaine blood levels, with the risk of serious side effects. Therefore, this treatment takes place only in a clinical setting.

Moreover, for virtually all pulmonary COVID patients, repeatedly coming to the hospital is too burdensome. To enable safe home treatment, a modified formulation has therefore been developed in which the excipient hydroxypropyl-β-cyclodextrin (HP-β-CD) has been added to lidocaine.

The aim of this formulation is that lidocaine, after subcutaneous administration, is preferably absorbed via the lymphatic system and less into the bloodstream, enabling patients to safely self-inject it at home. Additionally, HP-β-CD makes the injections less painful and allows the active dose to be administered in a smaller injection volume, which further reduces the risk of absorption into the bloodstream.

The safety, side effects, and outcomes of this modified lidocaine treatment were investigated in 103 patients with pulmonary COVID, who were monitored intensively and daily. These data have recently been scientifically published.

In contrast, the home injection of standard lidocaine infusion fluid has not been studied and is strongly advised against for safety reasons. General practitioners and medical specialists are therefore advised to administer lidocaine infusion fluid exclusively within the hospital.

No. This concerns a dispensed pharmacy preparation: a standard procedure whereby, in collaboration between the treating physician and the pharmacist, an existing registered active substance (lidocaine) is prepared with an excipient for a specific dosage form. The active molecule (API) remains unchanged. This therefore means no new molecule and no new active substance.

Medical care at Excellent Care Clinics is reimbursed under a DBC for pain medicine. However, the lidocaine preparation for home administration is currently not yet reimbursed by health insurers.

The cost of this medication currently amounts to approximately €3,000 per month and must, for the time being, be paid by the patient themselves. These costs are expected to decrease substantially when production can take place on a larger scale.

Excellent Care Clinics and other involved parties are committed to broader availability and future reimbursement of this treatment. Due to the high and urgent demand for care from patients in the Netherlands, a formal request has been submitted to Zorgverzekeraars Nederland for a temporary provision for this patient group.

Because the treatment has not yet been formally registered, reimbursement through basic insurance will only be possible after additional research and registration procedures have been successfully completed. As is customary in drug development, this process may take a considerable amount of time.