Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically ill Patients

A Two Center Propensity-Score Matched Study

Khalid Al Sulaiman; Ohoud Aljuhani; Abdulrahman I. Al Shaya; Abdullah Kharbosh; Raed Kensara; Alhomaidi Al Guwairy; Aisha Alharbi; Rahmah Algarni; Shmeylan Al Harbi; Ramesh Vishwakarma; Ghazwa B. Korayem


Crit Care. 2021;25(363) 

In This Article


The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a threat to public health worldwide.[1] Symptoms of COVID-19 manifest as a cluster of mild to severe respiratory symptoms.[1] Severe COVID-19 amplifies the overall systematic inflammatory response in critically ill patients, increasing the risk of multi-organ dysfunctions, acute respiratory disease syndrome (ARDS), and mortality.[1–4] This inflammatory response is caused by the hyperactivation of chemokines and cytokines, prominently interleukin-6 (IL-6).[5] Therefore, the dysregulation of cytokines was one of the targets for many treatment strategies in treating patients with severe COVID-19.[3]

To date, no specific pharmacological agents have proven efficacy against SARS-CoV; instead, host-directed therapies and supportive therapy are used.[5] The current treatment options for critically ill patients with COVID-19 include anti-viral agents, immunosuppressive agents, and immunomodulators.[6] However, the evidence about these treatment options' mortality benefit in critically ill patients with COVID-19 is conflicting.[7–10] Moreover, some mineral supplements and vitamins with immunomodulatory activity and antioxidant effects such as thiamine, vitamins C and D, zinc, and selenium use in patients with COVID-19 are investigated[11–14]

Zinc is a trace element that plays a role in the development and function of the immune system exhibiting direct or indirect anti-viral properties.[13,14] High intracellular zinc levels were reported to stall the replication of coronavirus (SARS-CoV-2) and influenza virus that caused the severe acute respiratory syndrome.[14–16] Some reports demonstrate the synergistic effect of zinc with anti-viral therapy in SARS-CoV-2.[17] The benefit of zinc supplementation on the immune system function has been previously observed in non-COVID-19 patients.[17,18] However, there is inadequate evidence to support the use of zinc for COVID-19 treatment in critically ill patients.[19,20] Yet, providers continue to use it as adjunctive therapy in this patient population. Therefore, we aim to evaluate the efficacy and safety of zinc supplementation as adjunctive therapy in treating critically ill patients with COVID-19.