This is a continuation of our discussion on the treatment and management of COVID-19 and infectious diseases in general. We’ll start with specific information on immunotherapies regarding their use in infectious diseases (I hope you reviewed some of the previous blogs mentioned last week addressing immunotherapeutic drugs and procedures. If not, it’s not too late.)
Immunotherapy
Antiviral drugs and some immunotherapeutics show beneficial effects in the early phases of the disease and monoclonal antibodies, biologics, and corticosteroids in the later phases during the potentially more aggressive immune/inflammatory stages. Monoclonal antibodies are also used asap upon infection. When administered early in the infectious period they serve as an effective antiviral agent to reduce the viral load in the nasopharynx. The effects of monoclonal antibodies and other drugs on viral load may prove to be an important criterion for the development of agents to treat early Covid-19.
Monoclonal antibodies and biologics:
Bamlanivimab (effective in early stages);
Combination of casirivimab plus imdevimab (most effective in early stages and high risk for progressing to severe disease and/or hospitalization);
Interleukin-6 receptor antagonists (suppressing ILK-6);
Tocilizumab and sarilumab have also been shown to improve outcomes and survival rates, especially when used in combinations;
Regeneron (combination of casirivimab and imdevimab called REGN-COV2, effective in early stages);
Bamlanivimab (LY-CoV555) is a single monoclonal antibody (delivered in 3 doses of 700 mg, 2800 mg, and 7000 mg);
Cytokine inhibitor drugs (e.g., checkpoint inhibitors, IgG, Interleukin 6 blockers) are being studied and beginning to show some benefits in advanced cases and late-stage infectious diseases and COVID-19.
Convalescent plasma (serum)
Plasma is collected from the blood of patients who have recovered from COVID-19. The red and white blood cells are separated and put back into the donor’s bloodstream while the blood plasma, rich with virus-fighting antibodies are kept aside. Monoclonal antibodies are isolated from patients and showed that the patients had strong immune responses against the infecting viral protein, a complex that binds to receptors on the host cell. From this information, a subset of antibodies from the serum can be used to neutralize the virus. Nonetheless, the results of convalescent plasma treatment continue to be equivocal.
Dexamethasone (and glucocorticosteroids)
A readily available, inexpensive corticosteroid, dexamethasone, has been found to improve survival in hospitalized patients who require supplemental oxygen and demonstrate elevated levels of inflammatory biomarkers. For patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. Several therapeutic interventions have been used to mitigate inflammatory organ injury (see chronic inflammation discussion in Blog #16) in viral pneumonia including glucocorticoids (i.e., dexamethasone). They have been widely used in syndromes closely related to Covid-19, including SARS, MERS, severe influenza, and community-acquired pneumonia. The evidence to support or discourage the use of glucocorticoids under these conditions is inconclusive. Other steroids are also beginning to show some promising results during the early stages of the disease.
CRISPR-Cas13 and RNA screening
A new Cas13 RNA screen (vs. Cas 9 from Blog #26) has been developed to establish guide RNAs for the COVID-19 coronavirus and human RNA segments that could be used in vaccines, therapeutics, and diagnostics. Similar to CRISPR-Cas9, a novel Cas13-based editing tool targets mRNA (vs. DNA for the Cas9 enzyme) and knockout genes without altering the genome. Using the CRISPR-Cas13 enzyme, researchers have created a genetic screen for RNA, currently designed for use in humans that they say could also be used on RNA containing viruses and bacteria. Developers have used the parallel-screening technique to create optimal guide RNAs for the SARS-CoV-2 coronavirus that could be used for future detection and therapeutic applications.
Discussion Questions:
If the early phase of SARS-CoV-2 is the most infectious and the late phase, the most inflammatory, what are suggested examples of the most appropriate therapy for each phase?
Different from CRISPR-Cas9, CRISPR-Cas13 is used to establish guide RNAs for the coronavirus and human RNA segments that could be used in vaccines, therapeutics, and diagnostics. What is the essential difference between the two technologies?
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