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 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.

BACKGROUND: An outbreak of pneumonia associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then to other city. It is very urgent to delineate the epidemiological and clinical characteristics of these affected patients. METHODS: To investigate the epidemiological characteristics of the COVID-19, a cross-sectional study was executed with 459 patients with confirmed COVID-19 in WZ of China from January 27 to February 12, 2020. RESULTS: The median age of all patients was 48.0 years, and 46.8% were females. 37.5% of patients had a history of residence in Wuhan. Fever (72.1%) and cough (43.6%) were the most frequent symptoms. In addition, three kinds of unconventional cases were observed, in which included 4.4% confirmed virus carrier who were asymptomatic, 7.8% confirmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 10.7% confirmed patients who had no link to Wuhan city nor a history of intimate contact with patients or individuals from Wuhan without any symptoms, respectively. CONCLUSIONS: Our findings presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and this phenomenon suggested that chances of uncontrollable transmission in the larger population might be higher than formerly estimated, and transmission by these three kinds of unconventional patients in WZ may be one of the characteristics of infection in other Chinese cities outside the Wuhan epidemic area.

BACKGROUND: An outbreak of pneumonia associated with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) was initially emerged in Wuhan city, and subsequently spread throughout China. Then the epidemic is rapidly circulating in a few other countries at present. So it is very urgent to delineate the clinical characteristics of these affected patients. METHODS: To investigate the epidemiological characteristics of this new Coronavirus Disease 2019 (COVID-19), a cross-sectional study was executed with 459 patients with confirmed COVID-19 in Wenzhou, China, from January 27 to February 12, 2020. RESULTS: The median age of all patients was 48.0 years, and 46.8% were females.