Humoral immune mechanisms involved in protective and pathological immunity during COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is associated with excessive inflammation, as a main reason for severe condition and death. Increased inflammatory cytokines and humoral response to SARS-CoV-2 correlate with COVID-19 immunity and pathogenesis. Importantly, the levels of pro-inflammatory cytokines that increase profoundly in systemic circulation appear as part of the clinical pictures of two overlapping conditions, sepsis and the hemophagocytic syndromes. Both conditions can develop lethal inflammatory responses that lead to tissue damage, however, in many patients hemophagocytic lymphohistiocytosis (HLH) can be differentiated from sepsis. This is a key issue because the life-saving aggressive immunosuppressive treatment, required in the HLH therapy, is absent in sepsis guidelines. This paper aims to describe the pathophysiology and clinical relevance of these distinct entities in the course of COVID-19 that resemble sepsis and further highlights two effector arms of the humoral immune response (inflammatory cytokine and immunoglobulin production) during COVID-19 infection.

Risk factors for adverse outcomes of COVID-19 patients: Possible basis for diverse responses to the novel coronavirus SARS-CoV-2.

Severe coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is characterized by an unpredictable disease course, with variable presentations of different organ systems. The clinical manifestations of COVID-19 are highly variable ranging from mild presentations to severe, life-threatening symptoms and the wide individual variability may be due to the broad heterogeneity in the underlying pathologies. There is no doubt that early management may have a major influence on the outcome. This led the scientists to search for ways to monitor disease progression or to predict outcomes in COVID-19. Although it is not yet possible to predict who will progress to the severe forms or in what time, numerous prospective and longitudinal studies represent the evidence for determining the potential immunological risk factors of COVID-19 critical disease and death. The kinetics and breadth of immune responses during COVID-19 appear to follow a trend which is consistent to the predominant pathological alterations. Recent publications have used these biomarkers to help identify patients who will develop the severe acute COVID-19. Of particular interest is the relationship between the kinetics of peripheral leukocytes and clinical progress of the disease in COVID-19. Although research is ongoing in this area, we present details about the current status of the evaluation. Understanding of the COVID-19 related alterations of the innate and adaptive immune responses may help to promote the vaccine development and immunological interventions.

Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients.

BACKGROUND: As an ongoing worldwide health issue, Coronavirus disease 2019 (COVID-19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients. METHOD: Forty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1ß, IL-6, TNF-α and IL-18 were assessed by Real-time PCR and ELISA, respectively. RESULT: Our primary results indicated that the mRNA expression and cytokine secretion of IL-1ß, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1ß gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin. CONCLUSION: Nano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1ß and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.

Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances.

The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.