Damian Sendler: Zinc deficiency has been linked to a greater risk of respiratory viral infections [1]. Because of this, researchers are testing zinc as a nutritional supplement for the prevention and treatment of coronavirus disease 2019 (COVID-19) infection, either alone or in combination with other minerals [2]. Zinc’s well-documented involvement in avoiding cell damage and its anti-viral capabilities are useful in understanding the possible role of zinc in COVID-19 treatment [3]. In addition, symptoms of zinc insufficiency and COVID-19 have certain similarities.
Damian Jacob Sendler: Zinc deficiency, like severe COVID-19 progression, has far-reaching effects on the neurological, cardiovascular, thymic, immunological, and endocrine systems [4]. Decreased hair follicles and skin lesions are among the immediate symptoms of zinc deficiency [5]. [5] As a result of chronic inflammation, zinc deficiency has been linked to an increased risk of cardiovascular disease, diabetes, rheumatoid arthritis, neurodegenerative illness, and obesity [6–8]. The higher risk of COVID-19-related consequences has been linked to each of these illnesses. Patients who suffer from these diseases are more likely to have problems with fertility or conception than those who do not.
Damian Sendler
Miscarriages, premature deliveries, cesarean sections, and perinatal fatalities have all been reported in women who were infected with COVID-19 while pregnant. Since COVID-19 exposure causes epigenetic alterations on the male and female reproductive systems that are not recognized, reproduction during this period is very risky. Male and female gametogenesis have been shown to be negatively affected by COVID-19 [11]. As a result, the influence of SARS CoV-2 on embryo quality has yet to be completely studied in the sperm and the oocytes.
Reactive Oxygen Species, Cytokine Storm, and Zinc
Multiorgan damage in COVID19 infections is caused by an acute phase response and a cytokine storm. There is no limit to how much ROS that can be created by activating mitochondrial respiratory chain enzymes, cytochrome P450 enzymes, peroxisomal fatty acid metabolism, and flavoprotein oxidases when the cytokine storm floods the body. IL-6 and tumor necrosis factor (TNF ) are produced in response to COVID-19 infection, and these interleukins boost neutrophil myeloperoxidase activity (MPO) [12]. There is a direct link between excessive MPO activity and the generation of ROS, notably the extremely reactive hydroxyl radical (•OH), through the Fenton reaction.
Overproduction of inflammatory markers and ROS, either individually or together, affects the male and female reproductive systems in varying degrees. ROS such as •OH (t1/2 = 109 s), O2• (t1/2 = 5 s), and peroxynitrite (ONOO) (t1/2 = 10 20 ms) have been found to exert immediate and irreversible effects on the oocyte spindle and chromosomal alignment in embryos [14, 15]. Similarly, the alignment of microtubules and chromosomes in mammalian oocytes is affected by IL-6 exposure [16]. As a result, oocyte damage is dose-dependently caused by H2O2 and hypochlorous acid (HOCl) formed by neutrophil MPO-H2O2 systems [17, 18]. Although ROS and oxidative stress have been linked to lower conception rates and IVF/ICSI results in animals [19], this is not the case in humans.
Nitric oxide (NO), a crucial mediator of vasodilation and also an essential regulator of the quality and age of oocytes, may potentially be a contributing factor in COVID-19 severe instances. [20] Fig. 1 shows an example. As a consequence of O2•’s effect on nitric oxide availability, ONOO is formed which damages cells. An increase in reactive oxygen species (ROS) and their detrimental effects on NO are also induced by low levels of intracellular zinc, which leads to the dysfunction of zinc-dependent antioxidant proteins such as superoxide dismutase (SOD), catalases and glutathione (GSH), the formation of NO synthase dimers and the dysfunction of several zinc finger proteins, resulting in mitochondrial damage and amplifying oxidative stress [21, 22].
Damian Jacob Sendler
While inhibiting NADPH oxidase and the redox activity of iron and copper, zinc is also known to reduce ROS generation [23]. [24] Because of this, zinc deficiency has the ability to affect all organ systems throughout the course of COVID-19 illness and may potentially have long-term effects on the quality of oocytes and sperm. As a result, women who are trying to conceive may benefit from taking zinc supplements, particularly in the wake of the COVID-19 epidemic.
Damian Jacob Markiewicz Sendler: Greater risk of infection and subsequent problems, longer recovery time, slower wound healing and increased cell damage from the acute phase response are all associated with zinc deficiency. The symptoms of SARS CoV-2 infection and zinc insufficiency are quite similar. Oxidative stress-mediated by ROS and neutrophil MPO activity has been extensively documented in association with zinc deficiency in COVID-19 symptoms including loss of smell and taste [25]. One of the most common causes of diarrhea and pneumonia in children is zinc deficiency, according to an epidemiological study of childhood mortality. Zinc supplementation in SARS CoV-2 patients may also help explain how zinc supplementation may enhance outcomes.
COVID-19 patients might benefit from zinc supplementation, not only by reducing ROS but also by enhancing their immunological response to infection. To keep the cytokine storm under control, zinc inhibits NF-KB signaling and modulates T cell function. Zinc has been shown to inhibit the RNA polymerase of SARS-CoV in vitro, which has anti-viral characteristics. SARS COV-2’s receptor, angiotensin-converting enzyme 2 (ACE2), has been shown to be inhibited by zinc in indirect studies [27]. By inhibiting caspase-3,-6,-9, it also increases the cell’s resistance to apoptosis [28]. Zinc’s anti-viral capabilities are also linked to zinc-binding proteins known as metallothioneins (MTs), which store and transport zinc. The cysteine sulfur ligands of MTs are modified by reactive chemicals or oxidative stress, releasing zinc ions and increasing intracellular free zinc concentrations. Patients infected with flaviviruses (e.g., yellow fever, HCV) and alphaviruses have been shown to have an overexpression of MTs (Venezuela equine encephalitis virus).
Anti-viral signaling may be facilitated by the sequestration of zinc from viral metalloproteins by MTs [29]. Interferon-mediated immune response components such as zinc finger anti-viral protein (ZAP) attach to CpG dinucleotides in viral genomes [30]. As a result, ZAP suppresses viral replication and mediates the destruction of viral genomes. As a result, zinc’s significance in the immune response to viral infections is well-established [32]. Infection-related symptoms of viruses and viral illnesses such as rhinoviruses, herpesviruses, picornavirides, flavivirides, togaviridae, retrovirides (HIV), and papillomavirides have been shown to benefit from therapeutic zinc therapy in studies [33].
Damien Sendler: COVID19 zinc supplementation studies are restricted to one small retrospective research in hospitalized patients that failed to show a link between zinc supplementation and better prognosis or survival [34]. Despite the urgent need for bigger and more extensive research, zinc may be of little benefit after the patient is unwell enough to be hospitalized. Oxidative damage and ROS generation occur as a consequence of the cytokine storm once the proinflammatory response is activated in the patient. In zinc-deficient people, this would lead to zinc depletion more quickly.
Acute irreversible cell damage occurs when enzymes that aid in the removal of ROS elements stop working. When extensive acute and oxidative cell damage has occurred, zinc supplementation alone may not be enough to reverse the process. A pro-antioxidant effect of zinc replacement in the body may help slow the course of COVID-19 by reducing viral multiplication and minimizing cell damage if given to infected persons before to the onset of a cytokine storm.
Dr. Damian Jacob Sendler and his media team provided the content for this article.