Monoclonal Antibody Therapy for COVID-19

Monoclonal antibodies are laboratory-created proteins that replicate the immune system’s capacity to combat diseases such as SARS-CoV-2. Furthermore, SARS-CoV-2, like other infectious organisms, can change over time, resulting in specific therapies failing to act against particular variations, such as the Omicron. Monoclonal antibodies are medicinal agents being researched to treat COVID-19.

These drugs are frequently developed by isolating pathogen-specific B cells from patients who have just recovered from an illness. After identifying B cells, the genes for the immune globulin heavy and light chains are retrieved. These genes are then activated, resulting in the production of monoclonal antibodies. Monoclonal antibodies (mAbs)prevents patients from potentially dangerous and adverse effects, including allergic reactions, from particular therapy drugs that are generally not anticipated to benefit people susceptible to or diagnosed with the Covid -19’s Omicron variant. 

Monoclonal antibodies have unique activity against a specific target and differ from convalescent plasma, composed of polyclonal antibodies in serum produced from individuals recovering from an illness. Besides HIV, influenza, RSV, MERS-CoV, Ebola, and Zika virus, other viral diseases have been treated and prevented by monoclonal antibodies. 

Only monoclonal antibodies targeting RSV and Ebola have proven effective in human studies, with the former having FDA approval from the US Food and Drug Administration (FDA). Several treatments aimed at the various viruses described above are now being tested in clinical studies. In nonhospitalised individuals, monoclonal antibodies are particularly successful at treating mild to severe COVID-19 infection.

Nonetheless, mAbs have been in scarce availability throughout the CoronaVirus epidemic. Patients at greater risk of being hospitalised or dying from COVID-19, such as the elderly and those with chronic diseases, are prioritised under federal standards. Throughout the COVID-19 epidemic, the FDA has used the best available research to make informed decisions with the public’s health and safety in mind. The agency’s first aim is to ensure that front-line healthcare practitioners have the most effective tools available to treat people.

Monoclonal Antibodies Against SARS-CoV-2

The genome of SARS-CoV-2 encodes four vital structural proteins: 

• Spike (S)
• Envelope (E)
• Membrane (M)
• Nucleocapsid (N), as well as nonstructural and auxiliary proteins 

The spike protein is further subdivided into two subunits, S1 and S2, responsible for host cell adhesion and invasion. S1 interacts with angiotensin-converting enzyme 2 (ACE2) on the host cell via its receptor-binding domain (RBD), causing a conformational shift in S2 that leads to virus-host cell membrane fusion and viral entry. 

Antibodies attach to certain amino acid sequences that are generally 5 – 8 residues long. These sequences are referred to as “epitopes.” Monoclonal antibodies bind to a single epitope, whereas polyclonal antibodies attach to multiple epitopes. This is due to the fact that each monoclonal antibody is derived from a single hybridoma cell line, whereas each polyclonal antibody is really a collection of antibodies produced in response to an immunogen.

Anti-SARS-CoV-2 monoclonal antibodies (mAbs) targeting the spike protein have been clinically beneficial in treating SARS-CoV-2 infection. Some anti-SARS-CoV-2 mAbs are effective post-exposure prophylaxis (PEP) following possible SARS-CoV-2 exposure in the home and during CoronaVirus epidemic. Other anti-SARS-CoV-2 mAbs have been proven to lower infection risk when used as pre-exposure prophylaxis (PrEP).

Anti-SARS-CoV-2 Monoclonal Antibodies for the Treatment of COVID-19

The following suggestions and discussion are limited to the use of approved anti-SARS-CoV-2 mAb products to treat COVID-19. The Omicron, which contains multiple mutations in the spike protein, has significantly decreased in vitro sensitivity to several anti-SARS-CoV-2 mAbs, particularly bamlanivimab plus etesevimab and casirivimab plus imdevimab. In vitro activity of sotrovimab against the Omicron, the variant is maintained.

Recommendations:

• The COVID-19 Treatment Guidelines Panel (the Panel) suggests using sotrovimab 500 mg as a single intravenous (IV) infusion, which should be administered as quickly as possible and within ten days of symptom onset, to treat non-hospitalised patients with mild to severe COVID-19 who are at high risk of clinical progression. 
• Since the Omicron variant has become the prevalent strain globally, the real-time testing to identify current uncommon, non-Omicron variants are not easily accessible, the panel advises against combining bamlanivimab with etesevimab .
• Anti-SARS-CoV-2 mAb treatment should begin as soon as SARS-CoV-2 infection is established by an antigen test or a nucleic acid amplification test (NAAT) and within ten days of initial diagnosis.
• If individuals with mild to moderate COVID-19 who are hospitalised for a cause other than COVID-19 fulfil the EUA requirements for outpatient therapy, treatment option with anti-SARS-CoV-2 mAbs should be investigated.

• Anti-SARS-CoV-2 mAbs are currently not approved for use in patients hospitalised with severe symptoms of COVID-19; nevertheless, the products may be available through expanded access programmes for patients who have not developed an antibody specific response SARS-CoV-2 infection or are not anticipated to mount an immune response to infection.
• There is no data on the use of antiviral medications in conjunction with anti-SARS-CoV-2 mAbs to treat COVID-19 in non-hospitalised individuals. Clinical studies and research are yet to evaluate if doctors can use this combination medication to treat COVID-19.
• Severely immunocompromised individuals may have more prolonged SARS-CoV-2 replication, resulting in faster virus development. According to this theory, the use of a single anti-SARS-CoV-2 mAb in these individuals may result in the generation of resistant viruses. More research is needed to determine its risks. The relevance of sotrovimab in combination with antiviral medication in the treatment of COVID-19 remains unknown.
• In non-hospitalised patients with mild to severe COVID-19 symptoms and specific risk factors for development of the diseases, using anti-SARS-CoV-2 mAb antibodies lowered the risk of hospitalisation and mortality in randomised placebo-controlled studies. These experiments were carried out before the broad distribution of the Delta and Omicron variants.

Anti-SARS-CoV-2 Monoclonal Antibodies Selection Criteria Under the Emergency Use Clause Authorisations

The FDA (Emergency Use Authorization) EUA for anti-SARS-CoV-2 mAbs lists particular diseases that put patients at high risk of clinical progression. The FDA updated the EUAs on May 14, 2021, to widen these requirements. The body mass index (BMI) criterion was lowered from 35 to >25, and additional criteria and variables were included (e.g., pregnancy, race or ethnicity). 

There are no longer any age restrictions on using these medications in patients with the following conditions: sickle cell disease, neurodevelopmental disorders, medical-related technology dependency, asthma, cardiovascular illness, hypertension, and chronic lung disease. The FDA is committed to reviewing new evidence on all COVID-19 medications linked to the possible impact of variations and revising authorisations to ensure healthcare practitioners have an effective arsenal of medications for patients. 

While it is vital to have the means to treat people who develop COVID-19, the permitted therapies are not a replacement for vaccination in individuals who require the COVID-19 vaccine and a booster dose. Various studies clearly show that accessible, safe, and effective immunisations can reduce your chance of getting COVID-19 and suffering the potentially devastating illness progression, including hospitalisation and death.

Visit the Helvitica Health Care website to explore our comprehensive range of monoclonal and polyclonal antibodies against infectious agents.