A CLOSER LOOK
EDITORIAL ADVISOR : Chad T . Rodgers , MD , FAAP , CPE
Role of Monoclonal Antibodies in COVID 19 : A Changing Landscape
T he earliest application of antibodies for the treatment of infections can be traced back to the late part of the 19th century , with the use of sera for the treatment of diphtheria 1 . This crude treatment was later replaced by purified antibodies from pooled sera , intravenous immunoglobulin . Monoclonal antibodies are another approach to fighting viral infections . These are laboratory-made proteins that mimic a person ’ s immune system ’ s ability to fight off harmful viruses . Monoclonal antibody therapy has been used extensively in viral infections , with Food and Drug Administration ( FDA ) approved products available for treating respiratory syncytial virus and ebola 1 .
Monoclonal neutralizing antibodies directed against severe acute respiratory syndrome coronavirus-2 ( SARS-CoV-2 ) spike protein have been developed by isolating B-cells from individuals recovered from COVID-19 illness . DNA from these specific B cells is inserted into cell culture to mass-produce the antibodies in vitro . These monoclonal neutralizing antibodies can then be directly infused into patients . They
ATUL KOTHARI , MD , FIDSA 1 , 2 , 3 AND RYAN DARE , MD 2 , 4
bind to the virus particles blocking them from entering human cells or tagging the virus antibody complex for destruction by the immune system 2 .
In November 2020 , the FDA issued emergency use authorization ( EUA ) of 2 products : bamlanivimab 3 and the combination of casirivimab and imdevimab ( REGEN-CoV ) 4 for the treatment of mild to moderate COVID-19 illness in patients 12 years of age or older at high risk of progressing to severe disease . Subsequently , in February 2021 , etesevimab received FDA EUA to be used with bamlanivimab 5 . Use of casirivimab / imdevimab or bamlanivimab / etesevimab has both been shown to decrease the risk of admission or 28-day mortality by 70 % 6 , 7 . The US Department of Health and Human Services ( HHS ) distributed these products free of cost .
In vitro studies have shown decreased activity of both bamlanivimab and bamlanivimab / etesevimab against beta and gamma variants 8 , 9 . With the increased circulation of these SARS-CoV-2 variants of concern in the United States , EUA for bamlanivimab was revoked ( April
2021 ) 10 , and shipments of bamlanivimab / etesevimab have been paused ( June 2021 ) 5 .
Most recently , sotrovimab was granted EUA by the FDA due to clinical trial data showing an 85 % risk reduction in hospitalizations or death within 28 days 11 , 12 . Thus , currently , there are two EUA monoclonal antibody products available to treat COVID-19 : REGEN-CoV ( distributed by HHS ) and Sotrovimab . Both products retain activity against the delta variant , which is the primary driver of cases nationally 8 , 12 .
As the evidence from different clinical trials has accumulated , the FDA has made several revisions to the original EUAs , expanding the criteria used to determine highrisk status in patients . Monoclonal antibodies are not authorized for use in patients hospitalized due to COVID 19 or those requiring oxygen therapy due to COVID-19 . In June 2021 , based on pharmacokinetic data , REGEN-CoV was authorized to be given by subcutaneous route in addition to intravenous infusion . In July 2021 , REGEN-CoV was authorized for post-exposure prophylaxis in certain high-risk settings ( Table 1 ).
108 • The Journal of the Arkansas Medical Society www . ArkMed . org