Potential role of GcMAF in suppressing the severity of COVID-19-induced immune responses: Lesson learned from HIV

Abstract

Over the last six months, there have been increasing numbers of reports that struggle to understand the pathogenesis of the coronavirus disease 2019 (COVID-19) pandemic. As of August 16, 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 21 294 000 infections and about 760 000 deaths worldwide [1], but the mechanisms of virus-induced host damage remain a mystery. Understanding the pathways behind viral pathogenicity just like cellular and tissue tropism, counteracting host defence processes and immunological responses are crucial to find new therapeutic strategies. Based on clinical reports, it is noteworthy that COVID-19 causes various degree of illness ranging from asymptomatic or milder symptomatic cases to severe lung injury or even multi-organ dysfunction with liver and kidney impairment [2], [3], [4]. Even in not severe patients, the heterogeneity of symptoms is consistent with the increasing evidence that SARS-CoV-2 shows a broad tissue tropism, being able to attack almost anything in the body [2], [3], [4], [5]. To date, the most commonly investigated hypothesis about the underlying mechanisms of multi-organ failure may be summarized into three main targets: microcirculation dysfunction, overwhelming inflammation and abnormal coagulation [7]. Radiologic and laboratory findings as well as preliminary autopsy studies seem to support this hypothesis. The most common patterns seen on chest CT were ground-glass opacity, interlobular septal thickening, air bronchogram, bilateral patchy shadowing, crazy-paving pattern, and thickening of the adjacent pleura, resembling an interstitial involvement in viral pneumonia [2], [3], [7], [8]. Under the light of microscope, the lungs revealed diffuse alveolar damage with formation of numerous hyaline membranes, very patchy and sparse interstitial chronic inflammation composed mainly of lymphocytes, thrombi within a few small pulmonary artery branches, congestion of alveolar septal capillaries, focal edema fluid, and macrophage infiltration within the airspaces [9], [10], [11], [12]. The more significant laboratory abnormalities were metabolic acidosis, lymphocytopenia, leukopenia, thrombocytopenia, elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH) and D-dimer [2], [3], [4], [5], [6], [7]. As firstly suggested by Huang C et al. [4], the systemic cytokine storm could play a key role in the virus-induced tissue damage. However, the question “what the link for the overproduction of pro-inflammatory mediators and the immune suppression, on the hand, and microvascular injury and thromboembolism, on the other, is”, remains unclear. Being the knowledge of this issue very scarce, lessons learned from other human pathogenic viruses, with specific reference to human immunodeficiency virus (HIV), could be diriment.