#16,118
Tomorrow afternoon (Aug 12th) the CDC will hold a one-hour COCA Call webinar on the use of monoclonal antibodies in the treatment of immunocompromised COVID cases.
Immunocompromised individuals are not only at greater risk of severe illness from COVID, they may remain infectious much longer than the 7 - 10 day average most people experience, which may allow new variants to arise.
I'll have considerably more on those concerns after the break.
COCA Calls are often technical, and are of greatest interest to clinicians and healthcare providers, but also may be of interest to the general public. As always, If you are unable to attend the live presentation, these (and past) webinars are archived and available for later viewing at this LINK. Details on tomorrow's presentation follow:Therapeutic Options to Prevent Severe COVID-19 in Immunocompromised People
Overview
The U.S. Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUA) for monoclonal antibodies to treat COVID-19 for certain patients. Monoclonal antibodies may be available through expanded access programs to treat COVID-19 for immunocompromised patients. However, the efficacy of use for immunocompromised patients is unclear.
During this COCA Call, presenters will discuss the FDA’s role in issuing EUAs for certain monoclonal antibodies, options for compassionate use, the process for ordering and distributing monoclonal antibodies, and current data on using monoclonal antibodies for both non-hospitalized and immunocompromised patients. Presenters will also cover preventing, diagnosing, and treating COVID-19 in immunocompromised patients, including the role of monoclonal antibodies, serologic testing, and potential third dose of COVID-19 vaccinations.PresentersElliot Raizes, MDTask Force LeadHealth Services and Worker Safety Task ForceCOVID-19 ResponseCenters for Disease Control and PreventionJohn Farley, MD, MPHDirector, Office of Infectious DiseasesCenter for Drug Evaluation and ResearchOffice of New DrugsU.S. Food and Drug AdministrationColin Shepard, MDCDC Liaison to the Assistant Secretary for Preparedness and Response (ASPR)Center for Preparedness and ResponseCenters for Disease Control and PreventionRajesh Gandhi, MDDirector, HIV Clinical Services and Education, Massachusetts General HospitalProfessor of Medicine, Harvard Medical SchoolAdi V. Gundlapalli, MD, PhDCo-Lead, Serology and Correlates of Protection Tiger Team, COVID-19 ResponseChief Public Health Informatics OfficerCenter for Surveillance, Epidemiology, and Laboratory ServicesCenters for Disease Control and PreventionRegistration is not required.Date: Thursday, August 12, 2021Time: 2:00 PM – 3:00 PM ETA few minutes before the webinar begins, please click the link below to join:Webinar ID: 161 225 4638Passcode: 980771Dial-in US: +1 669 254 5252 or +1 646 828 7666 or +1 669 216 1590 or +1 551 285 1373One-tap mobile: US: +16692545252,,1612254638#,,,,*980771# or +16468287666,,1612254638#,,,,*980771#International numbers available: https://www.zoomgov.com/u/adQOV17URbexternal icon
Last week the NEJM carried an article warning of the potential risk of new variants emerging from long-term infections among immunocompromised individuals (see SARS-CoV-2 Variants in Patients with Immunosuppression), a concern we've seen raised previously.
Last December, the ECDC Threat Assessment Brief On UK SARS-CoV-2 Variant speculated that the large number of concurrent mutations in the B.1.1.7 variant may have arised from a single chronically-infected, likely immunocompromised, individual.
B.1.1.7 lineage. This variant has 23 mutations with 14 amino acid replacements and 3 in-frame deletions which are listed in Table 1b. Two of these mutations have already been described to alter SARS-CoV-2 biology: N501Y sits in the receptor binding motif (RBM) of the Spike protein, and has been described to increase binding affinity to the human ACE-2 receptor; 69-70del has been identified in variants associated with immune escape in immunocompromised patients and is responsible for a “dropout” in the S gene PCR target in certain diagnostic tests (e.g. Thermo Fisher TaqPath). These tests target multiple regions of the virus genome, so the test itself is not compromised.
Reported cases and phylogenetic analyses have indicated an exceptional rate of introduction of mutations into this lineage. It has been hypothesised that this lineage may have resulted from the transmission of the virus from a chronically infected individual. This is based on observations that a high rate of mutations may accumulate in immunocompromised patients with chronic infections of SARS-COV-2.
About the same time, COG-UK released a report on multiple escape mutants generated in a chronically ill, immunocompromised patient, after receiving convalescent plasma therapy.
COG-UK: A Cautionary Tale On COVID Escape Mutants Generated In Patient Receiving Plasma Therapy
Below you'll find the press release from the Fred Hutchinson Cancer Research Center on their NEJM article mentioned above.
Persistent COVID-19 infections in immunocompromised people may give rise to variants of concern
Case studies in patients with prolonged COVID-19 disease mirror mutational patterns seen in some variants of concern Peer-Reviewed Publication
FRED HUTCHINSON CANCER RESEARCH CENTER
SEATTLE — August 4, 2021 — In an article in the New England Journal of Medicine, scientists from Fred Hutchinson Cancer Research Center, Johns Hopkins Bloomberg School of Medicine, the U.S. Military HIV Research Program and the Institute for Global Health and Infectious Diseases at the University of North Carolina urged increased attention to persistent COVID-19 infections in immunocompromised people.
“The medical community needs to develop more precise guidelines for monitoring, treating and preventing COVID-19 infections in immunosuppressed patients to reduce both the risk to these patients and the potential emergence of variants of concern,” said Dr. Larry Corey, virologist at Fred Hutch, leader of the COVID-19 Prevention Network and corresponding author of the article.The authors highlighted the importance of immunizing immunosuppressed patients, and among those with an inadequate response to vaccines, considering the use of prophylactic monoclonal antibodies to prevent infection. They advised healthcare providers to carefully monitor immunosuppressed people with persistent COVID-19 infections by using sequential samples to detect prolonged COVID-19 infections and the potential emergence of novel variants of concern. The partial immune response observed in immunocompromised people creates the unique environment for immune selection of evolutionary variants and is cause for concern, they wrote.
“The virus can persist for weeks or months in immunocompromised individuals, leading to viruses that carry a constellation of mutations – they sometimes look like the variants of concern that are currently threatening to our control efforts,” said Dr. Morgane Rolland, a viral geneticist with the U.S. Military HIV Research Program at Walter Reed Army Institute of Research and senior author of the article.Immunocompromised people should be informed about the potential for prolonged viral shedding if they’re infected with SARS-CoV-2 and the importance of self-isolation until they receive a negative test, the authors recommend. Prioritizing vaccination in these groups and among their households is critical, but access to highly effective COVID-19 vaccines must increase globally to meet this need.The authors also called for more focused research in immunocompromised groups. Immunologic studies in subsets of people with weakened immune systems, like solid organ transplant recipients, could help healthcare providers prevent severe and prolonged COVID-19 in these groups. Understanding the antibody and T-cell responses immunocompromised people could also give clues to why they can have a weakened antibody response to the virus’s spike protein.“A very large number of patients have difficulty mounting a defense against COVID-19 and will benefit greatly from ongoing and focused efforts to develop more robust COVID-19 treatment and prevention strategies,” commented Dr. Myron Cohen, associate vice chancellor for Global Health and Medical Affairs at the University of North Carolina and co-author of the article.Looking forward, the authors advocate for increased momentum in developing new COVID-19 vaccines and treatments. Efforts to develop next-generation vaccines that are more effective against variants, test antibody combinations that can prevent infection in immunosuppressed people and advance treatments that can stop viral replication, especially in these vulnerable populations, will be necessary to control the pandemic.
You can find more information on the use of monoclonal antibodies in the NIH's August 4th update of their Anti-SARS-CoV-2 Monoclonal Antibodies page.
