Monoclonal antibody therapy, also called monoclonal antibody infusion treatment, is a novel therapy that has demonstrated clinical benefits for patients with acute COVID-19.
This is a form of treatment that uses antibodies to target specific molecules, such as surface proteins on a virus that has infected the body. For example, the combination of two monoclonal antibodies, casirivimab and imdevimab, has been designed to bind to the spike protein of SARS-CoV-2.
When these antibodies attach to the spike protein, the virus cannot enter and infect the body’s cells. A combination of two antibodies is used to prevent resistance to the active substance through mutations.
The treatment is currently approved for use in the European Union and Switzerland for the treatment of confirmed COVID-19 in adults and adolescents who do not require oxygen therapy or hospitalization due to COVID-19. Prophylactic use of the antibody combination might be indicated in people who cannot produce an appropriate immune response to the virus.
A recent report indicated that this antibody cocktail might also be effective in treating patients with severe forms of Long COVID. In this case study, three patients with severe Long COVID experienced complete and long-term recovery within a week of receiving casirivimab plus imdevimab. This was independent of their age, sex, medical background, disease duration or vaccination status.
Each of the three patients participated in a standardized survey that collected their basic information, such as age, sex, and medical background. The survey also evaluated 33 signs and symptoms associated with Long COVID. Symptom severity was scored on scales ranging from “symptom not present” to “severe impact on daily life and ability to function”. Symptom scores were recorded for four periods: before COVID-19, during Long COVID, after COVID vaccinations and after monoclonal antibody therapy.
All three patients experienced complete recovery after antibody therapy.
The study included three previously healthy individuals who developed severe symptoms, including chronic fatigue and cognitive impairment, after recovering from acute COVID-19. All three received casirivimab plus imdevimab and experienced unexpected and complete recovery within a few days following this therapy. The patients have their symptoms fully resolved, returned to normal life, and maintained good health for over two years.
In more detail, the first patient was a 60-year-old woman in good health before SARS-CoV2 infection who developed acute COVID-19 in March 2020. She had temporary respiratory issues, cough, and fever.
After the acute infection, she developed a serious systemic syndrome, severe fatigue, chest discomfort, joint pain, and paresthesia (tingling, burning sensation in the limbs and skin; “pins and needles”). She also experienced memory difficulties, sleep disturbances and nightmares, occasional fever, and cognitive problems such as difficulties with reading and performing simple calculations.
Her Long COVID symptoms persisted after receiving COVID-19 vaccinations. In 2021, she received an infusion of casirivimab plus imdevimab and all Long COVID symptoms entirely diminished within four or five days. She sustained complete remission and has remained in good health for two years.
The second patient was a 43-year-old woman who was healthy except for a slightly lower number of red blood cells (anemia) and developed COVID-19 in 2021. After acute COVID-19 was resolved, she experienced severe fatigue, severe muscle and joint aches, shortness of breath, palpitations (feelings of having a fast-beating or pounding heart), significant dizziness, and concentration and memory difficulties.
The woman also had strong headaches, sensory changes (like taste and smell) and vivid dreams. Her symptoms did not improve after COVID-19 vaccinations. Following treatment with casirivimab plus imdevimab, all Long COVID symptoms entirely disappeared within five days, and she remained in remission for more than two years. No Long COVID symptoms returned even after reinfection with SARS-CoV-2.
The third patient was a 63-year-old man who had diabetes and high blood pressure but was generally in good health before COVID-19. After the acute phase of COVID-19, he developed severe fatigue, poor exercise tolerance and severe muscle aches.
He also experienced significant dizziness and severe difficulties with memory and concentration. Within a week after therapy with casirivimab plus imdevimab, his Long COVID symptoms significantly improved and remained absent for 24 months.
The authors of the study highlighted that family members of these three patients confirmed the sudden and complete improvements, which was surprising given the severity and long duration of their symptoms.
Mechanism of action of casirivimab and imdevimab. The two monoclonal antibodies bind to the receptor binding domain (RBD) of the spike protein on the surface of the SARS-CoV-2 virus and thereby hinder the virus from entering the cell. The RBD normally binds to the ACE2 receptor, allowing it to enter cells in our body (You can find a more detailed description of this mechanism in this blog). Adapted from Taylor et al.
What is the mechanism behind the recoveries?
The benefit of casirivimab and imdevimab might only apply to Long COVID resulting from the pre-Delta variants, since the antibodies were designed for these variants. The receptor binding domain mutates fast and therefore, antibodies designed for early variants do not have the same affinity to later variants.
Still, the three patient cases provide insights for treating and managing other post-viral chronic conditions, including Long COVID from other variants.
The authors proposed three theoretical pathways through which the infusion of monoclonal antibodies resulted in rapid and complete recoveries in these patients. According to the first one, the monoclonal antibodies neutralized persistent SARS-CoV-2 present in patients’ bodies; this reduction in viral particles helped the immune system to improve.
The second pathway suggests that the monoclonal antibodies displaced autoantibodies attached to special molecules on patients’ cells which caused removal of these autoantibodies from the body. Based on the third mechanism, monoclonal antibodies bound to molecules on immune cells which helped to eliminate remaining viral particles or cells infected with the virus.
While these results seem very promising, one has to keep in mind that they have only been reported in three people. To find out, whether a similar benefit can be achieved in a broader set of Long COVID patients, further, larger studies are needed.
