Delta this is updated from what I posted the other day. This is from one of the primary resources clinicians use to identify treatment protocols and is geared towards them. It talks about the plasma.
This isn't the whole thing, which is volumes covering all aspects of covid19. It's just a snippet to give a flavor. It's all foot noted as usual.
I grabbed the part about glucocorticoids as well. at one point they were thought to be effective in previous epidemics so were prescribed heavily out of hope.
Limited role of glucocorticoids — The WHO and CDC recommend glucocorticoids not be used in patients with COVID-19 pneumonia unless there are other indications (eg, exacerbation of chronic obstructive pulmonary disease) [13,82]. Glucocorticoids have been associated with an increased risk for mortality in patients with influenza and delayed viral clearance in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Although they were widely used in management of severe acute respiratory syndrome (SARS), there was no good evidence for benefit, and there was persuasive evidence of adverse short- and long-term harm [90]. (See "Treatment of seasonal influenza in adults", section on 'Adjunctive therapies' and "Middle East respiratory syndrome coronavirus: Treatment and prevention", section on 'Treatment'.)
The use of glucocorticoids among critically ill patients with COVID-19 is discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Critical care issues", section on 'Glucocorticoids'.)
Uncertainty about NSAID use — Some clinicians have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) early in the course of disease may have a negative impact on disease outcome [91,92]. These concerns are based on anecdotal reports of a few young patients who received NSAIDs early in the course of infection and experienced severe disease. However, there have been no clinical or population-based data that directly address the risk of NSAIDs. The European Medicines Agency (EMA) and the WHO do not recommend that NSAIDs be avoided when clinically indicated [93,94]. Given the uncertainty, we suggest acetaminophen as the preferred antipyretic agent, if possible, and if NSAIDs are needed, the lowest effective dose should be used. However, we do not suggest that NSAIDs be stopped in patients who are on them chronically for other conditions, unless there are other reasons to stop them (eg, renal injury, gastrointestinal bleeding).
Investigational approaches — A number of investigational approaches are being explored for antiviral treatment of COVID-19, and enrollment in clinical trials should be discussed with patients or their proxies. A registry of international clinical trials can be found on the WHO website and at clinicaltrials.gov.
Certain investigational agents have been described in observational series or are being used anecdotally based on in vitro or extrapolated evidence. It is important to acknowledge that there are no controlled data supporting the use of any of these agents, and their efficacy for COVID-19 is unknown.
●Remdesivir – Several randomized trials are underway to evaluate the efficacy of remdesivir for moderate or severe COVID-19 [95]. Remdesivir is a novel nucleotide analogue that has activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and related coronaviruses (including SARS and MERS-CoV) both in vitro and in animal studies [96,97]. Remdesivir is an intravenous agent; reported side effects include nausea, vomiting, and transaminase elevations. It is also prepared in a cyclodextrin vehicle, so there is concern for potentially toxic accumulation of the vehicle in renal impairment. Exclusion criteria vary by trials but include alanine aminotransferase level >5 times the upper limit of normal and chronic kidney disease (creatinine clearance <30 or <50 mL/min, depending on the trial); some trials also exclude use of a different COVID-19-targeted therapy within 24 hours prior to remdesivir initiation. The compassionate use of remdesivir through an investigational new drug application was described in a case report of one of the first patients with COVID-19 in the United States [98]. Any clinical impact of remdesivir on COVID-19 remains unknown.
●Chloroquine/hydroxychloroquine – Both chloroquine and hydroxychloroquine have been reported to inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity [99].
Clinical data evaluating hydroxychloroquine or chloroquine are limited, and their efficacy against SARS-CoV-2 is unknown. Nevertheless, given the lack of clearly effective interventions and the in vitro antiviral activity, some clinicians think it is reasonable to use hydroxychloroquine in hospitalized patients with severe disease or risk for severe disease who are not eligible for clinical trials. In the United States, the FDA issued an emergency use authorization to allow the use of these agents in adolescents or adults hospitalized for COVID-19 when participation in clinical trials is not feasible 💯. However, if these agents are used outside of a clinical trial, the possibility of drug toxicity (including QTc prolongation, in particular, as well as cardiomyopathy and retinal toxicity) and drug interactions should be considered prior to use, especially in individuals who may be more susceptible to these effects, and the patients should be monitored closely for adverse effects during use. The American College of Cardiology has suggested QTc monitoring parameters in this setting [101]. Optimal dosing is uncertain; the FDA suggests hydroxychloroquine 800 mg on day 1 then 400 mg daily and chloroquine 1 g on day 1 then 500 mg daily, each for four to seven days total depending on clinical response 💯. Other hydroxychloroquine regimens used include 400 mg twice daily on day 1 then daily for five days, 400 mg twice daily on day 1 then 200 mg twice daily for four days, and 600 mg twice daily on day 1 then 400 mg daily for four days [102].
Use of chloroquine is included in treatment guidelines from China's National Health Commission and was reportedly associated with reduced progression of disease and decreased duration of symptoms [103,104]. However, primary data supporting these claims have not been published [105].
Other published clinical data on either of these agents are limited. In an open-label study of 36 patients with COVID-19, use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment (70 versus 12.5 percent) [106]. In this study, the use of azithromycin in combination with hydroxychloroquine appeared to have additional benefit, but there are methodologic concerns about the control groups for the study, and the biologic basis for using azithromycin in this setting is unclear. In a randomized trial of 30 adults with COVID-19 in Shanghai, the proportion of patients with nasopharyngeal viral clearance at day 7 was not different with hydroxychloroquine (400 mg daily for five days) compared with standard of care, and one patient in the hydroxychloroquine group progressed to severe disease; interferon and other antiviral agents were used in both arms, which could be confounding factors [107].
●IL-6 pathway inhibitors – Treatment guidelines from China's National Health Commission include the interleukin (IL)-6 receptor inhibitor tocilizumab for patients with severe COVID-19 and elevated IL-6 levels. This agent, as well as sarilumab and siltuximab, which also target the IL-6 pathway, are being evaluated in clinical trials [108].
●Convalescent plasma – In the United States, the Food and Drug Administration is accepting emergency investigational new drug applications for use of convalescent plasma for patients with severe or life-threatening COVID-19 [109]. A case series described administration of plasma from donors who had completely recovered from COVID-19 to five patients with severe COVID-19 on mechanical ventilation and persistently high viral titers despite investigational antiviral treatment [30]. The patients had decreased nasopharyngeal viral load, decreased disease severity score, and improved oxygenation by 12 days after transfusion, but these findings do not establish a causal effect. Finding appropriate donors and establishing testing to confirm neutralizing activity of plasma may be logistical challenges. (See "Clinical use of plasma components", section on 'Convalescent plasma'.)
●Favipiravir – Favipiravir is an RNA polymerase inhibitor that is available in some Asian countries for treatment of influenza and is being evaluated in clinical trials for treatment of COVID-19. In a study of patients with non-severe disease (including oxygen saturation >93 percent), use of favipiravir was associated with faster rates of viral clearance (median time to clearance 4 versus 11 days) and more frequent radiographic improvement (in 91 versus 62 percent by day 14) compared with lopinavir-ritonavir [110]. However, other therapies were administered in this non-randomized, open-label study, so the results should be interpreted with caution given potential confounders.
●Lopinavir-ritonavir – Lopinavir-ritonavir appears to have little to no role in the treatment of SARS-CoV-2 infection. This combined protease inhibitor, which has primarily been used for HIV infection, has in vitro activity against the SARS-CoV [111] and appears to have some activity against MERS-CoV in animal studies [112]. However, there was no difference in time to clinical improvement or mortality at 28 days in a randomized trial of 199 patients with severe COVID-19 given lopinavir-ritonavir (400/100 mg) twice daily for 14 days in addition to standard care versus those who received standard of care alone [113].
