The challenges of treating COVID-19 in the face of different variants involve considerations of reduced vaccine effectiveness, increased transmissibility, potential resistance to treatments, and the need for ongoing surveillance and adaptation of countermeasures to combat the evolving virus(Planas et al. 2021; Tegally et al. 2021; Wang et al. 2021). These challenges highlight the importance of a multidisciplinary approach involving research, public health measures, and healthcare interventions to manage the pandemic effectively. The primary focus of this study, as well as many recent research endeavors, is to investigate the efficacy of suggested primary and adjunctive therapies as alternatives to target-specific treatments, given the reasons outlined above.

Five distinct variants (Alpha, Beta, Gamma, Delta, and Omicron) of SARS-CoV-2 have been recognized as significant global public health concerns (Meo et al. 2021). The most recent variant, Omicron, was initially identified on November 24, 2021, in South Africa and Botswana, and was subsequently designated as a novel variant by the WHO (Fan et al. 2022). The elevated number of mutations present in the Omicron variant of SARS-CoV-2 has the potential to impact the efficacy of existing vaccines and treatment protocols (Kandeel et al. 2022). As highlighted earlier, the Omicron variant poses a potential challenge to global endeavors aimed at controlling SARS-CoV-2 infections. Consequently, there is a compelling need for the meticulous design and execution of comprehensive clinical trial studies to identify effective and innovative therapeutic agents.

The objective of the present study was to assess the efficacy of NBS powder, a natural supplement, on the clinical condition and inflammatory markers of critically ill ICU patients suffering from ARDS attributed to the Omicron variant of COVID-19. Prior to the study, the definitive diagnosis of the Omicron variant of COVID-19 had been established through molecular-based testing and sequencing assays.

The comparative analysis within the control group exhibited a notable and statistically significant augmentation in the mean serum levels of CRP, ESR, D-Dimer, and CPK at the 14-day post-intervention, compared to the baseline. In the presence of inflammation, hepatic synthesis of CRP occurs, leading to its release into the bloodstream. Additionally, the ESR serves as an indicator of systemic inflammation within the circulatory system. The manifestation of pain, swelling, and erythema in affected tissues can be attributed to the production of CRP and elevation in ESR levels, commonly observed in the context of chronic diseases or autoimmune disorders (Sproston and Ashworth 2018). Inflammation can be triggered by a spectrum of conditions, encompassing bacterial or viral infections, arthritic disorders, vasculitis, and inflammatory bowel disease (Ahmed 2011). Elevated results in both the CRP and ESR tests are indicative of systemic inflammation within the body (Sproston and Ashworth 2018). Furthermore, D-Dimer has emerged as a noteworthy prognostic indicator for assessing the severity and mortality risk associated with COVID-19. Thromboembolic complications have been associated with elevated D-dimer levels, a phenomenon attributed not only to such complications but also to acute lung injury in the context of COVID-19 infection (Yao et al. 2020). CPK, an enzyme, naturally occurs in the body and is predominantly localized in the heart, brain, and skeletal muscle tissues. Elevated blood levels of CPK are indicative of injury or stress affecting the heart, brain, or muscle tissues (Kuwahara et al. 2010). Alterations in lymphocyte levels, characterized by increases and decreases, are clinically referred to as lymphocytosis and lymphocytopenia, respectively (Shanafelt et al. 2009). The findings of this study unveiled a notable decrease in mean serum lymphocyte levels at the 14-day post-standard antiviral treatment assessment within the control group, in comparison to the baseline measurements. Lymphocytes represent a pivotal component of the body’s immune system, tasked with combating foreign bacteria and viruses. Deviations in lymphocyte levels within the bloodstream, whether elevated or reduced, may bear relevance to underlying inflammatory processes (Jafarzadeh et al. 2021).

Conversely, our analyses unveiled a substantial decrease in the mean levels of CRP, ESR, D-Dimer, and CPK within the intervention group at the 14-day interval subsequent to NBS powder administration alongside standard antiviral treatment. A comparative assessment of the surveyed variables between the control and intervention groups showcased a statistically significant reduction in mean serum levels of CRP, ESR, D-Dimer, and CPK, at the 14-day post-intervention period within the intervention group, in contrast to the control group. This study unequivocally underscores the potent impact of a 14-day regimen of NBS consumption on the meticulous modulation of pivotal inflammatory markers within the body. These results not only corroborate the robust efficacy of NBS but also elucidate its pivotal role in significantly attenuating the levels of CRP, ESR, CPK, and D-Dimer. This effect is instrumental in alleviating life-threatening conditions in patients, as evidenced by recent research findings (Mehta et al. 2020; Ruan et al. 2020; Zhou et al. 2020). Emerging evidence suggests that the mechanism of action underlying this profound effect lies in NBS's ability to mitigate the excessive release of proinflammatory cytokines, curtail oxidative stress, and counteract the activation of pro-coagulation factors, all of which contribute to the amelioration of inflammation and, consequently, improved disease severity and reduced mortality rates among COVID-19 patients. These compelling findings emphasize the potential of NBS as an invaluable adjunctive therapy in the battle against severe COVID-19.

The impact of NBS powder on disease severity and immune system function in COVID-19 patients has been investigated in several rigorous scientific studies. In a clinical trial conducted by Jalilian et al. in Iran, the impact of NBS on immune system function in COVID-19 patients was thoroughly investigated. Their study revealed that the consumption of NBS powder over a duration of 4 weeks yielded a significant influence on the levels of proinflammatory cytokines, particularly interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), in individuals afflicted with COVID-19 (Azizi Jalilian et al. 2022). Furthermore, Mosadegh et al. conducted a meticulously designed study investigating the impact of NBS superfood on a spectrum of laboratory biomarkers and disease severity in patients afflicted with COVID-19. The findings derived from their rigorously executed clinical trial unequivocally demonstrated a significant decrease in the mean serum levels of key parameters, including CRP, ESR, D-Dimer, lactate dehydrogenase (LDH), aspartate aminotransferase (SGOT), serum glutamic pyruvic aminotransferase (SGPT), alkaline phosphatase (ALP), WBC count, IL-6, and TNF-α, at the 14-day interval following intervention compared to baseline within the intervention group (Mosadegh et al. 2022a, b). Another investigation revealed that the NBS supplement, administered orally to rats with rheumatoid arthritis, significantly reduced serum levels of inflammatory markers such as ESR and CRP. Moreover, it effectively normalized rheumatoid factor (RF) levels, indicating its potential to alleviate RA symptoms. These findings corroborate the anti-inflammatory properties of NBS observed in clinical trials on COVID-19 patients, underlining its broader therapeutic potential across inflammatory conditions. Further research is warranted to solidify its clinical value, but these collective results emphasize the promise of NBS as an adjunctive therapy for inflammatory diseases (Mosadegh et al. 2022a, b). These results underscore the significant impact of NBS superfood in mitigating inflammation and ameliorating disease severity among COVID-19 patients, in alignment with the findings of the present scientific research. The evaluation of disease severity and inflammatory biomarkers among COVID-19 patients has been a subject of investigation by various researchers, who have explored the potential effects of herbal supplements and pharmacological interventions. In a study conducted by Emadi et al. in Iran, the oral administration of Imatinib in hospitalized adults with COVID-19 was meticulously examined to assess its efficacy and safety profile. Their research findings shed light on the notable impact of Imatinib on modulating inflammatory markers, such as IL-6, within the patient population afflicted with COVID-19 (Emadi et al. 2020). The impact of curcumin-piperine supplementation on inflammatory markers, oxidative stress, clinical parameters, and mortality rates among critically ill patients in the ICU afflicted with COVID-19 was rigorously investigated by Askari et al. in a study conducted in Iran. Their comprehensive findings illuminated the favorable effects of curcumin-piperine supplementation, manifesting in the normalization of key clinical indicators including fever, blood oxygen saturation, and respiratory rate. Additionally, their research indicated that the utilization of curcumin-piperine supplementation exerted significant influence on important clinical outcomes, encompassing the duration of ICU stay, mortality rates, as well as the levels of prominent biomarkers such as CRP, ESR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, and creatinine (Askari et al. 2021). These findings contribute to the body of scientific knowledge about potential therapeutic interventions targeting inflammation and clinical outcomes in COVID-19 patients, aligning with the focus of the present study.

In a separate investigation conducted by Beigmohammadi et al. in Iran, the impact of vitamins A, B, C, D, and E on patient improvement and mortality rates within the context of COVID-19 was systematically evaluated. Their study illuminated the beneficial effects associated with vitamin consumption, particularly the modulation of key serum biomarkers including WBC count, CRP, ESR rate, IL-6, interferon-gamma (IFN-γ), and TNF-α (Beigmohammadi et al. 2020). These findings contribute valuable insights into the potential therapeutic role of supplementation in mitigating inflammatory responses and improving clinical outcomes among COVID-19 patients, aligning with the overarching objective of our investigation.

The findings of the present study have elucidated a notable disparity in mortality rates, whereby 31% of patients within the control group and 8.5% within the intervention group succumbed to the disease. This observation underscores the substantial impact of a 14-day regimen of NBS natural supplements in dramatically diminishing mortality rates among individuals afflicted with COVID-19. The mortality rate in the control group was substantially higher than in the intervention group, emphasizing the potential life-saving effects of NBS supplementation. While this study was not designed to explore the exact mechanisms underlying the reduction in mortality, it is plausible that the modulation of inflammation and immune response by NBS played a role in improving patient outcomes. One possible mechanism of NBS's action is its rich content of vitamins, minerals, and essential fatty acids. These nutrients are known to play roles in immune function and inflammation modulation. The diverse array of bioactive molecules in NBS may act synergistically to enhance the body’s defense mechanisms against the virus. Further research is needed to elucidate the specific mechanisms by which NBS exerts its effects.

The striking congruence observed in the outcomes of the present clinical trial and the antecedent investigations conducted by Jalilian et al. (Azizi Jalilian et al. 2022) and Mosadegh (Mosadegh et al. 2022a, b) attests to the robust and consistent efficacy of NBS superfood as an adjunctive therapeutic agent amidst the backdrop of distinct SARS-CoV-2 variants. It is of paramount significance to underscore the temporal context in which these studies transpired. While Jalilian’s inquiry centered on the alpha variant and Mosadegh’s exploration delved into the delta variant, the current trial unfolded amidst the tumultuous surge of the Omicron variant. The unwaveringly affirmative findings across this spectrum of viral strains lead us to a pivotal revelation: NBS’s mechanisms of action transcend the taxonomic boundaries of microorganisms, even in the face of the relentless mutational dynamics of emerging variants. This inherent adaptability delineates NBS as a unique and conceivably indispensable asset in the battle against infectious diseases, effectively countering the vexing challenges posed by the dynamic evolution of surface antigens in novel variants and the emergence of resistance phenomena. A foundational principle meriting recognition in the context of emerging viral variants resides in the potential attenuation of vaccine efficacy, frequently ascribed to the emergence of novel surface antigens and the subsequent evolution of antibody-resistant strains. These concerns have engendered a global reconsideration of therapeutic strategies, underscoring the urgency of innovative interventions. The extraordinary uniformity in the outcomes of the investigations by Jalilian, Mosadegh, and our present study underscores NBS as a beacon of optimism amidst these complex circumstances. It defies the conventional paradigms of pathogen-specific therapeutic modalities, presenting itself as a versatile and adaptable solution to the ceaselessly shifting landscape of viral variants. This profound attribute of NBS warrants further comprehensive examination and inquiry, as it may harbor the key to ameliorating the devastating consequences of emerging infectious diseases, fortifying our resilience in the face of the capricious forces of microbial evolution. As we confront the perpetual arms race between human scientific ingenuity and the adaptive abilities of viral entities, NBS emerges as a steadfast ally, offering a glimpse into the trajectory of pandemic preparedness and therapeutic innovation. The main limitation of the present study was budget limitation. The present study was a pilot study with a budget limitation. Therefore, we could not evaluate more biomarkers such as the levels of interleukins among included patients.

In conclusion, the present study has elucidated the capacity of NBS superfood supplement to effectively mitigate inflammatory markers in critically ill ICU patients afflicted by ARDS caused by the Omicron variant of COVID-19. These results underscore the potential utility of NBS superfood as an adjunct to standard antiviral treatments for inflammation reduction and the attenuation of mortality rates in COVID-19 patients.