A randomized, multicenter, open-label trial depicted that the combination of hydroxychloroquine, azithromycin, and zinc with or without vitamin C is effective and safe to treat coronavirus disease, with high dose intravenous vitamin C resulting in prompt recovery. Furthermore, vitamin D deficiency appears to be a high-risk factor of admisssion to intensive care unit and severe coronavirus disease.

This study aimed to determine the effectiveness and safety of hydroxychloroquine, azithromycin, and zinc with or without intravenous vitamin C in hospitalized people with SARS-CoV-2 for minimizing the severity and duration of symptoms and preventing death.

Hospitalized people with SARS-CoV-2 were screened for eligibility and randomized to receive either hydroxychloroquine, azithromycin, and zinc (group 1) or hydroxychloroquine, azithromycin, zinc plus intravenous vitamin C treatment (group 2) for fourteen days. The participants were also given nontherapeutic levels of vitamin D3.

The study recruited 237 hospitalized people infected with the coronavirus. Mortality or need for invasive mechanical ventilation at any time in the initial fifteen days from recruitment was the major endpoint. Almost all the participants were vitamin D deficient (97%), 55% were severely vitamin D deficient (less than 25 nmol/L) and 42% were vitamin D deficient (less than 50 nmol/L). Overall, 3% had insufficient levels of vitamin D (less than 75 nmol/L), and none had optimal levels of vitamin D.

In the study, 73% of the participants had comorbidities, including lung disease (34%), heart disease (36%), and diabetes (35%). All but 1 participant (99.6%; n = 236/237) treated with hydroxychloroquine, azithromycin, and zinc with or without high-dose intravenous vitamin C) was reported to fully recover. Additional intravenous vitamin C therapy contributed substantially to a prompt recovery (fifteen days versus forty-five days until discharge).

Adverse effects like vomiting, diarrhea, and nausea were reported by 15%-27% of the participants, were transient  and mild to moderate. There were no cardiac adverse effects.  The low levels of vitamin D were substantially correlated with longer hospitalization and a greater probability of admission to the intensive care unit. A 70-year-old female with heart and lung disease (vitamin D level of 6 nmol/L on hospitalization [severely deficient]) died after seventeen days in ICU and 22 days in the hospital. Future trials are needed to determine treatment with a combination of high-dose vitamin D3 in addition to hydroxychloroquine, azithromycin, and zinc and high-dose intravenous vitamin C.