Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options

McCreary, Erin K; Pogue, Jason M

To this point, Gautret et al [20] recently published their initial experience on the impact of 200 mg of hydroxychloroquine by mouth every 8 hours on viral eradication in patients with COVID-19. The authors reported on 36 patients (20 hydroxychloroquine and 16 control) who were COVID-19 positive and able to have nasopharyngeal sampling for the first 6 days of therapy (in the treated arm). The investigators demonstrated that hydroxychloroquine (14 of 20, 70%) was superior to standard of care (2 of 16, 12.5%; P = .001) in eradicating SARS-CoV-2 from the nasopharynx. It is interesting to note that 6 patients were prescribed azithromycin "to prevent bacterial super-infection" and the investigators found that viral eradication was numerically superior in this subgroup (6 of 6, 100%) compared with those who received hydroxychloroquine alone (8 of 14, 57%). The authors concluded that azithromycin "reinforced" the SARS-CoV-2 viral load achieved by hydroxychloroquine. Although these data are intriguing, certain limitations to this data set must be acknowledged. First, although viral eradication is an important endpoint, the authors did not report clinical outcomes in these patients. Second, the cohort initially contained 26 hydroxychloroquine patients, but 6 of them were removed from the analysis due to early cessation of hydroxychloroquine therapy including 3 PCR-positive patients who were transferred to the intensive care unit (ICU), 1 PCR-negative patient who passed away, and 1 PCR-positive patient who discontinued hydroxychloroquine due to nausea. Finally, the hydroxychloroquine monotherapy arm included patients with significantly higher viral loads, represented by lower cycle threshold (C T ) values than those who received combination therapy. If the hydroxychloroquine monotherapy patients with C T values <23 are separated from those with C T values ≥23, there is a notable discordance in viral eradication rates (1 of 5, 20% vs 7 of 9, 78%), with this latter number approaching the 6 of 6 demonstrated with hydroxychloroquine and azithromycin combination therapy in which all patients had C T values ≥23. Given this finding, the small numbers in this study, the lack of clinical outcomes presented, the potential for additive toxicity with hydroxychloroquine and azithromycin, and the desperate need to practice good antimicrobial stewardship during the COVID-19 pandemic, we would caution clinicians against using these data to support combination therapy.