Non-steroidal Anti-inflammatory Drugs (NSAIDs)/nitazoxanide/azithromycin Potential Beneficial COVID-19 Effects: Preventing the Cytokine Storm via Mitigation of the Interleukin-6 Amplifier and Monocytic Immunological Dysrhythmia.

Abstract

Recent genetic results demonstrated the important role of interferons and inflammation in COVID-19 pathogenesis and complications. Furthermore, a weak early interferon response to SARS CoV-2 infection triggers an exaggerated inflammatory response, to be noted that the unconstrained immunoinflammatory response is responsible for the COVID-19 associated mortality. We present a concise analysis of the cited genetic results that correlated COVID-19 with interferons and inflammatory genes according to our real-life and academic experience that disagree with some genetically based recommendations from a clinical and pharmacovigilant point of view. Importantly, nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response in our body as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, especially when early administered, have been hypothesized and practiced by the author to prevent COVID-19 complications and mortality due to their ability to constrain and prevent or reverse COVID-19 associated hyperinflammatory response and to mitigate the formation of several inflammatory cytokines and pathways including interleukin-6, NF-κB which are vital to develop the cytokine storm.

COVID-19 and Ebola Reclassification as Novel Acute Immune Deficiency Syndrome (n-AIDS): Potential Curative Role for Immunomodulators.

“…Taken together, we suggest that our suggested novel classification of acute immunedysrhythmic syndrome might properly guide us in our quest for a cure as it is only when we know the cause, we can figure out the cure and we recommend to focus on immunemodulation as a potential effective COVID-19 therapy [6,13,31], Ebola virus disease [32] and Nipah virus infection [25] and we hypothesize that our evolved real-life immunomodulatory COVID-19 management protocol [31] that guided us to this hypothesis through its remarkable clinical efficacy against COVID-19 might be also beneficial when tested in clinical trials for early management of other RNA viruses that cause n-AIDS as well as other diseases caused by altered Th1/Th2 balance.…”

“…Similarly, some COVID-19 patients will recover smoothly while others complain of post COVID-19 autoimmune complications hypothesized to be due to transient immunosuppression of innate and acquired immunity [12]. Moreover, we have recently suggested a new terminology for SARS CoV-2 induced dysregulated immune response; monocytic dysrhythmia [13] and an imbalanced immuneinflammatory response was previously described to drive development of COVID-19 [14]. Furthermore, we suggested to name para COVID-19 syndrome [15] to embrace a potential that SARS CoV-2 might persist latent, for yet unspecified period, in some cells and tissues [16] and/or a capability to induce immune-mediated disorders such as what is currently being described of several post COVID-19 diseases affecting the nervous system [17,18] or reactivation of various types of herpes viruses which are described in critically ill COVID-19 patients [19] and we recommend further investigations to assess potential SARS CoV-2 direct latency or indirect persistent functional dysrhythmia; respectively in some immune cells such as the migrating interstitial macrophages [20,21] as it is already well known how SARS CoV-2 possesses several adaptive differences from other coronaviruses to be noted that our knowledge about RNA viruses and their capabilities to remain latent for long duration is still evolving and it might eventually resemble the newly described latent Ebola virus [https://www.sciencemag.org/news/2021/03/new-ebolaoutbreak-likely-sparked-person-infected-5-years-ago ].…”

SARS CoV-2 Might Exploit Cells of the Innate Immune System to Induce the Novel Acute Immune Dysrhythmic Syndrome (n-AIDS) and Para COVID-19 Syndrome.

“…Importantly, we have recently suggested in a preprint that COVID-19, and other selected potentially fatal viral diseases, might be reclassified under a category of as immunopathological novel acute immune deficiency/ dysrhythmic Syndrome (n-AIDS) (Kelleni, 2021, March 25) and we have previously described an immunological monocytic dysrhythmia that plays a crucial role in development of the cytokine storm in another preprint that has been revised and is currently under consideration at a reputable journal (Kelleni, 2021, January 24) while suggesting further investigations for a potential latency of SARS CoV-2 in some of the immune system cells especially the migrating interstitial macrophages (Kelleni, 2021, March 25). Notably, we have previously postulated lymphocyte distraction into and/or away from the lungs to reason for the lymphopenia frequently encountered in COVID-19 and previously with SARS and we would like to present a combined theory to reason for COVID-19 pathogenesis especially in severe to critical cases that might also be determined, at least partly, on a genetic basis (Kelleni, 2021, January 19a).…”