The causal agent of the coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which belongs to the genus Betacoronavirus of the Coronaviridae family. Other coronaviruses that caused epidemics are SARS-CoV and MERS-CoV. SARS-CoV-2 is a positive-sense RNA genome, is extremely infectious, and has claimed more than 3.7 million lives worldwide. The transmission of the disease occurs via respiratory droplets from infected individuals.
Researchers have revealed that most of the COVID-19 patients are asymptomatic or show mild symptoms. However, about 20% of patients get severely infected and might suffer respiratory failure and cardiopulmonary collapse, which can be fatal. Scientists around the world have been working extensively to contain the pandemic. They have developed several vaccines and identified several therapeutic agents such as hydroxychloroquine, antibodies, chloroquine, corticosteroids, or convalescent plasma to treat COVID-19. However, some of the therapeutic agents identified thus far, such as hydroxychloroquine, chloroquine, and several antivirals, have already been rejected as potential COVID-19 treatments.
One of the approaches adopted for the treatment of COVID-19 is passive immunotherapy, which includes antibodies that use convalescent plasma therapy (CPT). In CPT, plasma is isolated from the hyperimmune patient and is transfused into a COVID-19 patient. Another treatment involves the use of therapeutic monoclonal antibodies (mAbs) or a cocktail of polyclonal antibodies (pAbs), which are biotechnologically engineered. Researchers have revealed that the use of mAbs is the foremost innovative approach that could prevent as well as treat infected patients. Several researchers are focusing on developing new cures based on specific mAbs to inhibit and/or neutralize SARS-CoV-2 in COVID-19 patients.
A new study has been published in the journal Vaccines that deals with the present state of research on using mAbs for the treatment of the COVID-19 disease. Many clinical trials are being conducted to evaluate the efficacy and safety of several newly designed mAbs. Some of the mAbs are directed towards immune system responses, i.e., non-SARS-CoV-2 specific mAbs, while others are devised to neutralize the SARS-CoV-2 protein structure, i.e., SARS-CoV-2 specific mAbs.
In hospitals, mAbs are being used to treat COVID-19 patients. Scientists have observed that one of the immune responses includes a sudden release of an enormous number of definite cytokines into circulation. This phenomenon is known as ‘cytokine storm,’ which can cause a severe systemic inflammatory syndrome. The main pro-inflammatory cytokines that are found in COVID-19 patients is IL-6. Thus, anti-IL-6/IL-6R drugs are prescribed to treat SARS-CoV-2 disease. Currently, mAbs such as tocilizumab, sarilumab, and siltuximab are being used to treat COVID-19 patients with high IL-6 levels.
Tocilizumab (TCZ) is a human IgG1 mAb drug that targets soluble as well as membrane-bound IL-6 receptors and blocks the signal mediated by them. This drug is also used to treat autoimmune diseases, e.g., rheumatoid arthritis and systemic juvenile idiopathic arthritis. One of the reasons why this drug is most frequently used for treating severely infected COVID-19 patients is its high availability. In various randomized clinical trials as well as in various observational studies, the safety and efficacy of TCZ in the treatment of COVID-19 are being further evaluated. The current research has reviewed sixteen published articles, and all the research statistically proves that the mortality rate has significantly reduced after TCZ administration in COVID-19 hospitalized patients.
Sarilumab is another human IgG1 mAb that also targets soluble and membrane-bound IL-6 receptors (IL-6Rα) and blocks the IL-6 induced signaling. Three ongoing and one completed clinical trials are associated with siltuximab, another mAb drug. However, preliminary studies have shown that this drug can be beneficial for COVID-19 patients, especially for respiratory failure.
Researchers have conducted phylogenetic analysis that has shown similarities in the genetic structure of SARS-CoV and SARS-CoV-2. The Spike (S) proteins of the virus are present on its surface and are a key component in the infection process. This protein mediates the penetration of the virus into the host cell by binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2). The majority of mAbs under development target the S protein. Some of the mAbs such as B38, H4, 47D11, and CR3022 can prevent COVID-19 infection.
Scientists have revealed that plasma from COVID-19 recovered patients can be a potential source for various specific SARS-CoV-2 mAbs that have neutralizing capacity. Researchers have identified that B38 and H4 could be favorable candidates for use as part of antibody-based prophylactic and therapeutic COVID-19 treatment. Further, 47D11 and CR3022 were reported to cross-neutralize SARS-CoV and SARS-CoV-2.
The Food and Drug Administration issued an Emergency Use Authorization (EUA) for certain mAbs, undergoing clinical trials, to be used for the treatment of COVID-19. The first mAb to receive an EUA from the FDA was bamlanivimab (LY-CoV555). However, later, the FDA revoked the EUA for bamlanivimab monotherapy owing to the emergence of SARS-CoV-2 variants, which are resistant to this treatment. Another mAb that received an EUA from the FDA is REGN-COV2, which is a combination cocktail of Casirivimab (REGN10933) and imdevimab (REGN10987).