The COVID-19 pandemic has caused a global health crisis, with no specific antiviral to treat the infection and the absence of a suitable vaccine to prevent it. While some individuals contracting the SARS-CoV-2 infection exhibit a well coordinated immune response and recover, others display a dysfunctional immune response leading to serious complications including ARDS, sepsis, MOF; associated with morbidity and mortality. Studies revealed that in patients with a dysfunctional immune response, there is a massive cytokine and chemokine release, referred to as the ‘cytokine storm’. As a result, such patients exhibit higher levels of pro-inflammatory/modulatory cytokines and chemokines like TNFα, INFγ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCSF, HGF and chemokines CXCL8, MCP1, IP10, MIP1α and MIP1β. Targeting this cytokine storm is a novel, promising treatment strategy to alleviate this excess influx of cytokines observed at the site of infection and their subsequent disastrous consequences. Natural immunosuppressant compounds, derived from plant sources like curcumin, luteolin, piperine, resveratrol are known to inhibit the production and release of pro-inflammatory cytokines and chemokines. This inhibitory effect is mediated by altering signal pathways like NF-κB, JAK/STAT, MAPK/ERK that are involved in the production and release of cytokines and chemokines. The use of these natural immunosuppressants as adjuvants to ameliorate the cytokine storm; in combination with antiviral agents and other treatment drugs currently in use presents a novel, synergistic approach for the treatment and effective cure of COVID-19. This review briefly describes the immunopathogenesis of the cytokine storm observed in SARS-CoV-2 infection and details some natural immunosuppressants that can be used as adjuvants in treating COVID-19 disease.

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27 October 2020, irrespective of type of article, country, or region. Joanna Briggs Institute’s design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.

The study of the use of nanotechnology for drug delivery has been extensive. Nanomedical approaches for therapeutics; drug delivery in particular is superior to conventional methods in that it allows for controlled targeted delivery and release, higher stability, extended circulation time, minimal side-effects, and improved pharmacokinetic clearance (of the drug) form the body, to name a few. The magnitude of COVID-19, the current ongoing pandemic has been severe; it has caused widespread the loss of human life. In individuals with severe COVID-19, immune dysregulation and a rampant state of hyperinflammation is observed. This kind of an immunopathological response is detrimental and results in rapid disease progression, development of secondary infections, sepsis and can be fatal. Several studies have pin-pointed the reason for this immune dysregulation; deviations in the signaling pathways involved in the mediation and control of immune responses. In severe COVID-19 patients, many signaling cascades including JAK/STAT, NF-κB, MAPK/ERK, TGF beta, VEGF, and Notch signaling were found to be either upregulated or inactivated. Targeting these aberrant signaling pathways in conjunction with antiviral therapy will effectuate mitigation of the hyperinflammation, hypercytokinemia, and promote faster recovery. The science of the use of nanocarriers as delivery agents to modulate these signaling pathways is not new; it has already been explored for other inflammatory diseases and in particular, cancer therapy. Numerous studies have evaluated the efficacy and potential of nanomedical approaches to modulate these signaling pathways and have been met with positive results. A treatment regime, that includes nanotherapeutics and antiviral therapies will prove effective and holds great promise for the successful treatment of COVID-19. In this article, we review different nanomedical approaches already studied for targeting aberrant signaling pathways, the host immune response to SARS-CoV-2, immunopathology and the dysregulated signaling pathways observed in severe COVID-19 and the current treatment methods in use for targeting signaling cascades in COVID-19. We then conclude by suggesting that the use of nanomedical drug delivery systems for targeting signaling pathways can be extended to effectively target the aberrant signaling pathways in COVID-19 for best treatment results.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had devastating global impacts since its emergence in late 2019. However, it also prompted an unprecedented scientific response (Cauchemez et al., 2024). While the acute phase of the pandemic has largely subsided due to quarantining, vaccination efforts and improved treatments, a new challenge has emerged in the form of post-COVID inflammatory syndromes. A hallmark of severe COVID-19 was excessive inflammation involving multiple organ systems, characterized by cytokine storms, coagulation dysfunction, and tissue damage. Even after recovery from acute infection, many patients continue to experience persistent inflammatory symptoms affecting various body systems, a condition now known as "long COVID" or "post-acute sequelae of SARS-CoV-2 infection" (PASC) (Barber et al., 2021, Davis et al., 2023; Liu et al., 2023; Porter et al., 2023).The complex nature of post-COVID syndromes presents a significant challenge to healthcare systems worldwide. Symptoms can vary widely between patients and may affect multiple organ systems, including the respiratory, cardiovascular, neurological, and gastrointestinal systems. Common complaints include fatigue, cognitive dysfunction ("brain fog"), shortness of breath, anxiety, depression, and sleep disturbances. The underlying mechanisms of these persistent symptoms are not fully understood but are thought to involve ongoing inflammation, autonomic dysfunction, and potential autoimmune processes triggered by the initial SARS-CoV-2 infection.Conventional medical approaches to treating post-COVID syndromes have shown limited success, highlighting the need for novel and integrative strategies. Natural products and plant-based medicines have a long history of use in treating inflammatory conditions and modulating immune function. Many of these compounds have well-documented anti-inflammatory, antioxidant, and immunomodulatory properties that could potentially address the multifaceted nature of post-COVID syndromes.The global impact of long COVID cannot be overstated. With millions of people worldwide experiencing persistent symptoms following SARS-CoV-2 infection, the social, economic, and healthcare burdens are immense. The development of effective treatments for post-COVID syndromes is therefore of paramount importance. As we continue to navigate the long-term consequences of the COVID-19 pandemic, interdisciplinary collaboration between conventional and complementary medicine will be crucial. By combining the strengths of various therapeutic approaches and diagnostic methods, we may be better equipped to tackle the complex challenges posed by post-COVID syndromes. The studies in this Research Topic demonstrate the potential of such integrative approaches and pave the way for future research in this critical area.This Research Topic explored innovative approaches to address post-COVID inflammatory syndromes using natural products, medicinal plants, nutrients, and integrative diagnostic methods. The articles in this collection investigate a range of natural compounds and plant-based medicines for their anti-inflammatory and immunomodulatory properties that may help alleviate lingering post-COVID symptoms. Additionally, the potential of nutritional interventions and traditional diagnostic techniques to support patients with post-COVID syndromes is examined.The research presented in this collection explores several promising avenues for natural interventions. These include the use of specific vitamins and nutrients to support immune function and reduce inflammation, herbal extracts with known anti-inflammatory properties, and comprehensive lifestyle interventions addressing diet and physical activity. By targeting multiple aspects of post-COVID syndromes simultaneously, these integrative approaches may offer advantages over single-target pharmaceutical interventions.Moreover, this Research Topic delves into the potential of traditional diagnostic methods to complement conventional techniques in assessing and monitoring patients with post-COVID syndromes. These approaches may provide valuable insights into the complex interplay of symptoms and underlying physiological imbalances, allowing for more personalized and holistic treatment strategies. As our understanding of post-COVID syndromes continues to evolve, this research provides valuable insights into natural therapeutic options that may work in concert with conventional treatments to improve outcomes for affected patients.1. Deng et al. examined the relationship between fat-soluble vitamin status and antibody responses to COVID-19 vaccination in a cohort of 141 healthy adults. They found that higher plasma vitamin D levels were associated with lower anti-SARS-CoV-2 antibody titers, both for wild-type and Omicron variants. This unexpected finding suggests that vitamin D may play a complex role in modulating vaccine-induced immunity, highlighting the need for further research on optimal vitamin D levels for vaccine efficacy.2. Pourfarzi et al. conducted a randomized controlled trial testing a web-based lifestyle intervention focused on nutrition and physical activity for preventing COVID-19. The study involved 303 women aged 30-60 who had not previously contracted COVID-19. The intervention group received online educational sessions on healthy diet and physical activity. After 4 weeks, the intervention group showed significant improvements in weight, BMI, nutritional status, and physical activity levels compared to controls. Importantly, the intervention group also had a lower incidence of COVID-19 infection during the follow-up period, suggesting that lifestyle modifications may help reduce COVID-19 risk.3. Gaylis et al. evaluated a nutraceutical supplement containing multiple compounds, including β-caryophyllene, pregnenolone, and various herbs and vitamins, for treating long COVID symptoms. In an open-label trial with 51 participants, the...

Tree nuts form an essential part of our diet. They are rich in proteins, fats and an array of micro and macronutrients and are also palatable and considered as a delicacy. Among all the tree nuts, the almond is often referred to as the king of nuts. This is because it contains high amounts of nutritive elements like monounsaturated fatty acids, minerals such as magnesium and copper, α-tocopherol and fiber making it an integral part of the diet. Almonds are known to reduce oxidative stress, inflammation and the risk of cardiovascular diseases and diabetes. The present study endeavored to determine the proximate composition of locally available tree almonds, Prunus amygdalus. The moisture content, ash value, iron, phosphorous, calcium, protein, fat and fiber levels were estimated by standard protocols. The results obtained were then correlated with previously described studies. The findings of this study were in line with previous studies. Locally available P. amygdalus was found to be a rich source of protein, fat, calcium and phosphorous. The moisture and ash content were low. The fiber content is moderate and amount of iron is considerably low. This makes locally available almonds a suitable, accessible and vital part of the diet.