Written 11/18/20
Challenges always present opportunities. As detrimental as the COVID-19 associated complication known as “cytokine storm” (see “The Eye of the Storm” for an introduction) is, it may also open up possible avenues for treatment of severe COVID-19 infections.
Despite all the contradictory and confusing information, at the time of this writing, the only treatments for COVID-19 that seem to be beneficial are remdesivir, monoclonal antibodies, convalescent plasma, and dexamethasone (with monoclonal antibodies just coming into play, convalescent plasma being used regularly with possible benefits, and the earlier much discussed hydroxychloroquine now on the therapeutic scrapheap). Interestingly, these therapies work in different ways and at different stages of the illness.
Remdesivir, monoclonal antibodies, and convalescent plasma may help patients early in their course of COVID-19 – when viral replication and infection are the predominant factors contributing to the illness. The therapies do not seem to benefit patients like Peggy, who reach a later stage dominated by the immune response to the infection.
Remdesivir is a drug that acts directly against the virus, the way our antibacterial antibiotics have been killing pathogens like Streptococcus for year. You probably had a shot for strep throat as a kid, but were told on another occasion that there were no antibiotics for the virus that caused your cold. That may soon change.
Monoclonal antibodies are designer antibodies created in a lab to be used against the virus the way our normal antibodies would, but given early in the course before the immune system has had a chance to ramp up its own antibody production. The idea is sort of like supplying an outgunned army with sophisticated military hardware early in a war until the country is able to ramp up its own production. Such a therapy was given to President Trump during his illness with coronavirus.
Another way to administer antibodies that neutralize the virus is to give some of the plasma (blood with the cells removed) from patients recovering from COVID. In theory this plasma fluid should be rich in antibodies – someone else’s antibodies – against SARS-CoV-2. This approach to therapy is analogous to one country sending its battle-hardened troops as mercenaries to help another military force with little experience against its invading enemy.
Dexamethasone only seems to help when given later in the course of COVID-19. It may even be harmful if given earlier in the sickness, before the patient has low oxygen and pneumonia. This medication is a corticosteroid, which acts in the same way as the cortisol produced by your own adrenal glands.
Corticosteroids (you may also hear them called “glucocorticoids” or simply “steroids”) like dexamethasone suppress the immune system. They are cheap and widely available medications. They give a strong “Hold your fire” order to white blood cells. That is why timing of the medication is so important. Holding your fire in the heat of the battle or failing to hold it when the fight is over are both detrimental.
In addition to dexamethasone, we already have a stable of immune-modifying drugs to treat numerous afflictions related to an over-enthusiastic immune system, those “autoimmune diseases,” like lupus and rheumatoid arthritis.
“Repurposing” of existing drugs used to treat other immune-mediated conditions may save the lives of some of the sickest patients in the pandemic. For example an immune suppressing drug being developed to treat psoriasis was approved in the summer of 2020 in India to treat severely ill COVID-19 patients, after a small trial of 30 patients showed a benefit in those given the drug compared to those who were given only a placebo.
There are ongoing studies of other medications which inhibit specific cytokines. It is hoped that this treatment could jam or modulate the dysfunctional signals between overzealous members of the immune system and reduce the severity of COVID-19 infections in those with cytokine storm.