[Updated 22 October] Let’s face reality: at the beginning of the second pandemic wave, we have some steroids which have been shown to reduce mortality in patients with severe COVID-19 (see Corticosteroids, page 131); and then we have a drug, remdesivir (Veklury®), which had a marginal benefit in a company-sponsored trial (Beigel 2020). That’s the COVID-19 treatment armamentarium as of October 2020.
Thus, the next 35 pages will discuss many drugs that have shown so far NO effect. So why read this chapter? Because doctors need to know the state-of-the-art – even the ‘state-of-the-non-art’. Doctors must know why substances have shown NO effect and why there may still be new, innovative and creative ideas; why the senior physician has been less enthusiastic about tocilizumab over the last few weeks and why the 89-year-old diabetic on Ward 1 still gets remdesivir and famotidine; and why the plasma therapy did not work in the 51 yrs old obese woman who died on Ward 2.
Hopefully, within a few months, this chapter will contain only ten pages. We only need one good drug (or, for that matter, five me-too-drugs). Only one drug that must not even be perfect but could become a game changer in this pandemic (perhaps even more so and even sooner than a vaccine) because good enough to prevent people from becoming seriously ill. One drug to downgrade SARS-CoV-2 to the rank of their stupid seasonal common cold siblings nobody was really interested in during the last decades (except Christian Drosten).
Research activity is immense. A brief look at ClinicalTrials.gov illustrates the efforts that are underway: on April 18, the platform listed 657 studies, with 284 recruiting, among them 121 in Phase III randomized clinical trials (RCTs). On October 14, these numbers have increased to 3,598, 1,880 and 230. Unfortunately, many trials exclude those patients most in need: the elderly. A data query of ClinicalTrials.gov on June 8 revealed that 206/674 (31%) COVID-19 interventional trials had an upper age exclusion criterion. The median upper age exclusion was 75 years. Exclusion of older patients dramatically increases the risk of non-representative trial populations compared with their real-world counterparts (Abi Jaoude 2020).
Different therapeutic approaches are under evaluation: antiviral compounds that inhibit enzyme systems, those inhibiting the entry of SARS-CoV-2 into the cell and, finally, immune therapies, including convalescent plasma and monoclonal antibodies. Some immune modulators may enhance the immune system, others are supposed to reduce the cytokine storm and associated pulmonary damage that is seen in severe cases. In this chapter, we will discuss the most promising agents (those for which at least a bit of clinical data is available). We will not mention all compounds that may work in cell lines or that have been proposed from virtual screening models. We will also forget some.
On the following pages, the following agents will be discussed:
* * * The complete chapter will be available soon. * * *