Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
Journal of Medical Microbiology, doi:10.1099/jmm.0.001250
Introduction. COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin. Aim. To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone. Methodology. This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19. Results. Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (n=411) and patients taking hydroxychloroquine and azithromycin alone (n=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and 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 sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12-2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449,.
Conclusion. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.
Funding information The authors received no specific grant from any funding agency.
Conflicts of interest The authors declare that there are no conflicts of interest.
Acevedo-Murillo, León, Firo-Reyes, Santiago-Cordova, Gonzalez-Rodriguez, Zinc supplementation promotes a Th1 response and improves clinical symptoms in fewer hours in children with pneumonia younger than 5 years old. A randomized controlled clinical trial, Front Pediatr
Barnett, Hamer, Meydani, Low zinc status: a new risk factor for pneumonia in the elderly?, Nutr Rev
Cao, Wang, Wen, Liu, Wang, A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Faber, Gabriel, Ibs, Rink, Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response, Bone Marrow Transplant
Gautret, Lagier, Parola, Hoang, Meddeb, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Geleris, Sun, Platt, Zucker, Baldwin, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Hemilä, Zinc lozenges may shorten the duration of colds: a systematic review, Open Respir Med J
Huang, Wang, Li, Ren, Zhao, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet
Jayawardena, Sooriyaarachchi, Chourdakis, Jeewandara, Ranasinghe, Enhancing immunity in viral infections, with special emphasis on COVID-19: a review, Diabetes Metab Syndr
Krenn, Gaudernak, Holzer, Lanke, Kuppeveld, Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections, J Virol
Li, Geng, Peng, Meng, Lu, Molecular immune pathogenesis and diagnosis of COVID-19, J Pharm Anal
Maares, Haase, Zinc and immunity: an essential interrelation, Arch Biochem Biophys
Magagnoli, Narendran, Pereira, Cummings, Hardin, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, medRxiv
Molina, Delaugerre, Goff, Lima, Ponscarme, No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection, Med Mal Infect
Prasad, Zinc in human health: effect of zinc on immune cells, Mol Med
Read, Obeid, Ahlenstiel, Ahlenstiel, The role of zinc in antiviral immunity, Adv Nutr
Science, Johnstone, Roth, Guyatt, Loeb, Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials, CMAJ
Skalny, Rink, Ajsuvakova, Aschner, Gritsenko, Zinc and respiratory tract infections: perspectives for COVID-19 (review), Int J Mol Med
Velthuis, Van Den Worm, She, Sims, Baric et al., Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture, PLoS Pathog
Who, Coronavirus disease
Xue, Moyer, Peng, Wu, Hannafon, Chloroquine is a zinc ionophore, PLoS One
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis
Zhang, Liu, Potential interventions for novel coronavirus in China: a systematic review, J Med Virol