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Evidence Suggests Therapeutic Role for Zinc Sulfate with Hydroxychloroquine for COVID-19.

Abstract. A summary of a study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.

As COVID-19 continues to spread, the mortality rate rises, as well as significant widespread economic losses. New potential therapies and means of prophylaxis against COVID-19 are urgently needed to combat this novel infection. A new in vitro study out of NYU Langone investigates the outcomes amongst patients who received hydroxychloroquine and azithromycin alone compared to those who received triple therapy with zinc sulfate, finding that when zinc sulfate is added in triple therapy outcomes among hospitalized patients may improve.

In response to in vitro evidence suggesting zinc sulfate may be efficacious against COVID-19, NYU Langone Hospitals began using zinc sulfate as an add-on therapy to hydroxychloroquine and azithromycin, performing a retrospective observational study to compare hospital outcomes among patients who received hydroxychloroquine and azithromycin plus zinc versus hydroxychloroquine and azithromycin alone. NYULH categorized patients based on their exposure to hydroxychloroquine (400 mg load followed by 200 mg twice daily for five days) and azithromycin (500 mg once daily) alone or with zinc sulfate (220 mg capsule containing 50 mg elemental zinc twice daily for five days) as treatment in addition to standard supportive care. Data was collected from electronic medical records for all patients being treated with admission dates ranging from March 2, 2020 through April 5, 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. Patients in the study were excluded if they were treated with other investigational medications. 

In NYULH's univariate analysis, the addition of zinc sulfate to hydroxychloroquine and azithromycin was not associated with a decrease in length of hospital stay, duration of mechanical ventilation, maximum oxygen flow rate, average oxygen flow rate, average fraction of inspired oxygen, or maximum fraction of inspired oxygen during hospitalization. In addition, they found that the addition of zinc sulfate was associated with likelihood of discharge to home in univariate analysis. In bivariate logistic regression analysis, the addition of zinc sulfate was associated with decreased mortality or transition to hospice, as well as the need for ICU and need for invasive ventilation. However, after excluding all non- critically ill patients admitted to the intensive care unit, zinc sulfate no longer was found to be associated with a decrease in mortality. Thus, this association was driven by patients who did not receive ICU care. 

Altogether NYULH's results suggest that the addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration and increased the frequency of patients being discharged home, as well as the decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, The addition of zinc sulfate led to a constant reduction in mortality or transfer to hospice, suggesting that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.

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