Monoclonal Antibodies: A Designer COVID-19 Treatment Requires Designer Rehabilitation
Monoclonal antibodies aren’t new. While we may currently be using them experimentally to treat patients in the early phases of COVID-19 infection, they have been around since 1985. You may already be familiar with a few of them. For instance, we treat Crohn’s disease with adalimumab and non-Hodgkin’s lymphoma with rituximab.
Monoclonal antibodies come in several different forms, and new ones are created nearly every day due to the interesting naming system used to identify them. The common suffix for the drug class (-mAb) is an acronym that stands for monoclonal Antibodies. These drugs can help us combat many illnesses, but also come with serious side effects that may be long term and influence our treatment choices.
So what does this mean for rehab professionals like physical therapists and occupational therapists?
How Do Monoclonal Antibodies Work?
How these drugs work is pretty simple. Monoclonal antibodies are chosen or designed to have the highest affinity for a given target. There is literally a “library” of choices and countless options for purchase. What makes them “monoclonal” is that each antibody is exactly identical in its protein structure and, therefore, should have the exact same affinity, effects, and efficacy within a given batch.
COVID-19 is not the first virus we’ve treated with monoclonal antibodies. There are monoclonal antibody treatments for both Ebola and respiratory syncytial virus (RSV) that are safe and effective.
Monoclonal antibodies are mostly famous for their use in treating various types of cancers and rheumatological conditions. These drugs are favored due to their ability to block tumor necrosis factor, one of the main inflammatory agents in our bodies, but this also causes immunosuppression. We don’t yet know if the monoclonal antibodies used to treat COVID-19 will have immunosuppressant effects.
Currently there are two monoclonal antibody infusions available under emergency use authorization for the treatment of COVID-19:
- A combination treatment of casirivimab and imdevimab, given authorization on November 21, 2020 (Named REGEN-COV)
- Sotrovimab, given authorization on May 26, 2021
A third treatment—bamlanivimab—was previously available but was withdrawn on April 16, 2021, due to ineffectiveness.
As of publication, neither treatment is FDA approved, and both are still being extensively studied in patients with mild to moderate COVID-19 symptoms who are not hospitalized, do not require supplemental oxygen, and meet a host of other criteria, including comorbidities, weight, and age restrictions. These antibodies have been designed to specifically attack the spike protein that COVID-19 is known for and have shown ability to reduce viral load at 28 days post-treatment.
What Do These Treatments Mean for My Patients?
Monoclonal antibodies are in no way a fool-proof treatment for COVID-19. These drugs are unpredictable, as each one is completely unique and can produce individualized side effect profiles in each patient. Side effects can occur at any time, from during treatment up to several weeks or months after treatment.
Many patients may be seeing their PT or OT long after their acute medical condition has been treated with monoclonal antibody therapies, especially in the cases of long COVID. Therefore, PTs and OTs should be informed of the common side effect profiles of monoclonal antibody therapy.
Most often, people who have reactions to monoclonal antibodies display:
- Skin reaction at the infusion site, including itching, redness, rash, bruising, and the potential for cellulitis
- Muscle pain
- Hyperhidrosis (sweating profusely)
More serious reactions can include:
- Bronchospasm or shortness of breath
- Hypersensitivity reactions
- Bradycardia or tachycardia
Between the potential for cardiotoxicity, immunosuppression, and the cardiovascular and pulmonary (not to mention other systems) effects of COVID-19 infection and sequelae, it stands to reason that physical therapists and occupational therapists need to plan for the prescription of cardiovascular and pulmonary retraining as part of their interventions for patients after COVID-19. This may be more difficult in the presence of long COVID, as fatigue can set in with minimal activity.
What Can I Do to Help These Patients?
Early evidence from the CDC and the APTA demonstrates the importance of setting baseline exercise capacity using standardized outcomes measures, such as the two-minute step test, and a quality-of-life report measure, such as the PROMIS or Post-COVID-19 Functional Status Scale. However, post-exertional malaise needs to be monitored and individually accounted for when performing these assessments and prescribing subsequent exercise programs.
High-intensity interval training has been theorized as a method of exercise intervention for patients after COVID-19 due to its ability to reduce multiple inflammatory factors, including those responsible for the COVID-related “cytokine storm.” High-intensity interval training has multi-system benefits, including improved overall aerobic function down to the subcellular level and beneficial structural adaptations to the cardiovascular system. Multiple clinical trials and studies have been registered with promising results of high-intensity interval training for improved viral clearance and physical outcomes in patients experiencing post-COVID and long-COVID symptoms, but most studies have small sample sizes and treatment with monoclonal antibodies has not been a distinguishing factor.
Application of high-intensity interval training may prove difficult on a larger scale due to the post-exertion malaise that may follow training in those experiencing long COVID. However, some evidence exists for inverted (or low volume) protocols for other types of post-viral syndromes where the lower-intensity intervals are significantly longer than high-intensity intervals. What is clear is that a gradual return to activity is warranted, and that this “gradual” return may be significantly longer than we are used to.
When it comes to post-COVID rehabilitation, low and slow is likely to be the tempo.
- American Physical Therapy Association. (2021, June 21). CDC long COVID guidance acknowledges the unknown, stresses patient assessment. https://www.apta.org/news/2021/06/21/cdc-long-covid-guidance
- Batacan Jr., R. B., Duncan, M. J., Dalbo, V. J., Tucker, P. S., & Fenning, A. S. (2017). Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies. British Journal of Sports Medicine, 51(6), 494–503. https://doi.org/10.1136/bjsports-2015-095841
- Christensen, R. H., & Berg, R. M. G. (2021, March 19). Vascular inflammation as a therapeutic target in COVID-19 "long-haulers": HIITing the spot? Frontiers in Cardiovascular Medicine, 8:643626. https://doi.org/10.3389/fcvm.2021.643626
- Cohen, P., & Blau, J. (2021, July). COVID-19: Outpatient evaluation and management of acute illness in adults. UptoDate. https://www.uptodate.com/contents/covid-19-outpatient-evaluation-and-management-of-acute-illness-in-adults?topicRef=3970&source=see_link
- Denay, K. L., Breslow, R. G., Turner, M. N., Nieman, D. C., Roberts, W. O., & Best, T. M. (2020). ACSM call to action statement: COVID-19 considerations for sports and physical activity. Current Sports Medicine Reports, 19(8), 326–328. doi: 10.1249/JSR.0000000000000739
- Emergency Care Research Institute (ECRI). (2021, March 11). Q&A: Monoclonal antibody therapy for the treatment of COVID-19 in nonhospitalized patients. https://www.ecri.org/components/PPRM/Pages/QAMonoclonalAntibodyCOVID19.aspx?PF=1&source=print
- Gerriets, V., Bansal, P., Goyal, A., & Khaddour, K. (2021, July 18). Tumor necrosis factor inhibitors. In: StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482425/
- Hermann, M., Pekacka-Egli, A.-M., Witassek. F, Baumgaertner, R., Schoendorf, S., & Spielmanns, M. (2020). Feasibility and efficacy of cardiopulmonary rehabilitation after COVID-19. American Journal of Physical Medicine and Rehabilitation, 99(10),865–9. doi: 10.1097/PHM.0000000000001549
- RECOVERY Collaborative Group. (2021, June 16). Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised controlled, open-label, platform trial. [unreviewed manuscript] medRxiv. https://www.medrxiv.org/content/10.1101/2021.06.15.21258542v1.full.pdf+html
- Regeneron. (2021, July 31). Frequently Asked Questions. https://www.regencov.com/patient/faq?utm_source=google&utm_medium=ppc&utm_campaign=Competitor&utm_content=Competitor&utm_term=sotrovimab&gclid=Cj0KCQjwjo2JBhCRARIsAFG667Vrx_2VBXdI6VL-QqAMubY3OwVYR-3SCfmeqy1QAkTidJDzXMLYjxIaAgjyEALw_wcB
- US Food and Drug Administration. (2020, November 21). Coronavirus (COVID-19) update: FDA authorizes monoclonal antibodies for treatment of COVID-19. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19
- US Food and Drug Administration (FDA). (2021, April 16). Coronavirus (COVID-19) update: FDA revokes emergency use authorization for monocloncal antibody bamlanivimab. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab
- US Food and Drug Administration. (2021, May 26). Coronavirus (COVID-19) update: FDA authorizes additional monoclonal antibody for treatment of COVID-19. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19