Activation of Inflammasome complex in nasopharyngeal epithelial cells from patients with Coronavirus disease 2019 contributes to inflammatory state and worse disease outcomes.

Pathogenesis of Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of both adaptive and innate immune systems. Hence, we determined the contribution of inflammasome in the nasopharyngeal epithelial cells isolated from COVID-19 subjects to disease pathogenesis and outcomes. Epithelial cells from 150 COVID-19 patients and 150 healthy controls were yielded through nasopharyngeal swab sampling. Patients were categorized into three groups of those with clinical presentations/need hospitalization, with clinical presentations/no need hospitalization and cases without clinical symptoms/no need hospitalization. Finally, the transcriptional amount of inflammasome related genes were assessed in the nasopharyngeal epithelial cells using qPCR. There was a significant upregulation of nod-like receptor (NLR) family pyrin domain containing 1 (NLRP1), nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), Apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase-1 mRNA expressions in patients compared to controls. NLRP1, NLRP3, ASC and Caspase-1 were upregulated in epithelial cells of patients with clinical symptoms/need hospitalization and cases with clinical symptoms/no need hospitalization when compared to controls. There was a correlation between expression of inflammasome-related genes and clinicopathological features. Abnormal expression of inflammasome-related genes in the nasopharyngeal epithelial cells obtained from COVID-19 patients may be of prognostic value to determine the intensity of the disease's outcomes and requirement for alternative supports in hospitals.

The prevalence and contributing risk factors of coronavirus disease 2019 infection in patients with metabolic syndrome.

BACKGROUND: Components of metabolic syndrome (MetS) was reported to contribute to severe and worse outcomes of coronavirus disease 2019 (COVID-19). Hereby, we evaluated the association of MetS and its components with susceptibility to COVID-19. METHODS: Here, 1000 subjects with MetS were recruited that were diagnosed via the International Diabetes Federation (IDF) criterion. Real-time PCR was exerted to detect SARS-CoV-2 in the nasopharyngeal swabs. RESULTS: Among the MetS patients, 206 (20.6%) cases were detected to have COVID-19. Smoking (OR = 5.04, 95%CI = 3.53-7.21, P < 0.0001) and CVD (OR = 1.62, 95%CI = 1.09-2.40, P = 0.015) were associated with increased chance of COVID-19 infection in the MetS patients. BMI was significantly higher (P = 0.0001) in MetS cases with COVID-19 than those without COVID-19. Obesity was associated with increased susceptibility to COVID-19 in MetS patients (OR = 2.00, 95%CI = 1.47-2.74, P < 0.0001). Total cholesterol, TG, LDL were significantly higher in the MetS cases with COVID-19 than those without COVID-19. Dyslipidemia was associated with increased chance of COVID-19 (OR = 1.50, 95%CI = 1.10-2.05, P = 0.0104). FBS level was significantly higher in the MetS cases with COVID-19. T2DM was associated with increased risk of COVID-19 in MetS patients (OR = 1.43, 95%CI = 1.01-2.00, P = 0.0384). Hypertension was associated with increased chance of COVID-19 in the MetS patients (OR = 1.44, 95%CI = 1.05-1.98, P = 0.0234). CONCLUSIONS: MetS and its components, like obesity, diabetes, dyslipidemia, cardiovascular complications were associated with increased chance of COVID-19 infection development and probably with aggravated symptoms in such patients.

Nasopharyngeal epithelial cells from patients with coronavirus disease 2019 express abnormal levels of Toll-like receptors.

Aberrant activation of the immune system has been attributed with etiology and pathogenesis of coronavirus disease 2019 (COVID-19). Here, the transcript levels of toll-like receptors (TLRs) were measured in the nasopharyngeal epithelial cells obtained from COVID-19 patients to assess the involvement of these molecules in the clinical outcome of COVID-19 patients. Nasopharyngeal swab samples were used to obtain epithelial cells from 120 COVID-19 patients and 100 healthy controls. COVID-19 cases were classified into those having clinical symptoms/needing for hospitalization, having clinical symptoms/not needing for hospitalization, and those without clinical symptoms|. The mRNA expression levels of TLRs were measured in the nasopharyngeal epithelial cells. Overall, mRNA expression of TLR1, TLR2, TLR4, and TLR6 was significantly higher in COVID-19 cases compared to controls. The mRNA expression of TLRs were all higher significantly in the samples from COVID-19 patients having clinical symptoms and needing hospitalization as well as in those with clinical symptoms/not needing for hospitalization in comparison to controls. TLR expression was significantly higher in those with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization compared to COVID-19 cases without clinical symptoms. In cases with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization, there was a correlation between TLR expression and clinicopathological findings. In conclusion, aberrant expression of TLRs in the nasopharyngeal epithelial cells from COVID-19 cases may predict the severity of the diseases and necessity for supportive cares in the hospital.

mRNA expression of toll-like receptors 3, 7, 8, and 9 in the nasopharyngeal epithelial cells of coronavirus disease 2019 patients.

BACKGROUND: The etiopathogenesis of coronavirus disease 2019 (COVID-19) stem partially from the abnormal activation of the innate and adaptive immune systems. Here in the current investigation, the mRNA expression levels of toll-like receptors (TLRs) were evaluated in the nasopharyngeal epithelial cells from COVID-19 patients. METHODS: Epithelial cells were obtained using nasopharyngeal swab samples from 90 COVID-19 patients and 50 controls. COVID-19 cases were classified into those without symptoms, with symptoms but not hospitalized, and with symptoms and hospitalized. To determine the mRNA expression levels of TLRs, first RNA was extracted and cDNA was synthesized, and finally Real-time PCR was exerted. RESULTS: It was seen that the transcript levels of TLR3, TLR7, TLR8, and TLR9 were overexpressed in the COVID-19 patients with clinical symptoms needing hospitalization as well as in those with clinical symptoms without needing for hospitalization compared to controls. Upregulation of TLRs was associated with clinical presentations of the patients. CONCLUSIONS: Modulation of TLR3, TLR7, TLR8, TLR9 in the epithelial cells of COVID-19 cases may estimate the disease severity and requirement for hospitalization.

The prognostic value of S100A calcium binding protein family members in predicting severe forms of COVID-19.

BACKGROUND: Excessive inflammation has been implicated in the immunopathogenesis of coronavirus disease 2019 (COVID-19). In the current study, the involvement of S100 calcium binding protein S100A4, S100A9, and S100A10 in the inflammatory settings of COVID-19 patients were evaluated. METHODS: Peripheral blood samples were obtained from 65 COVID-19 subjects and 50 healthy controls. From the blood samples, RNA was extracted and cDNA was synthesized, and then the mRNA expression levels of S100A4, S100A9, and S100A10 were measured by Real-time PCR. RESULTS: The mRNA expression of S100A4 (fold change [FC] = 1.45, P = 0.0011), S100A9 (FC = 1.47, P = 0.0013), and S100A10 (FC = 1.35, P = 0.0053) was significantly upregulated in COVID-19 patients than controls. The mRNA expression of S100A4 (FC = 1.43, P = 0.0071), (FC = 1.66, P = 0.0001), and S100A10 (FC = 1.63, P = 0.0003) was significantly upregulated in the severe COVID-19 subjects than mild-to-moderate subjects. There was a significant positive correlation between mRNA expression of S100A4 (ρ = 0.49, P = 0.030), S100A9 (ρ = 0.55, P = 0.009), and S100A10 (ρ = 0.39, P = 0.040) and D-dimer in the COVID-19 patients. The AUC for S100A4, S100A9, and S100A10 mRNAs were 0.79 (95% CI 0.66-0.92, P = 0.004), 0.80 (95% CI 0.67-0.93, P = 0.002), and 0.71 (95% CI 0.56-0.85, P = 0.010), respectively. CONCLUSIONS: S100A4, S100A9, and S100A10 play a role in the inflammatory conditions in COVID-19 patients and have potential in prognosis of severe form of COVID-19. Targeting these modules, hopefully, might confer a therapeutic tool in preventing sever symptoms in the COVID-19 patients.

Is there any relationship between serum zinc levels and angiotensin-converting enzyme 2 gene expression in patients with coronavirus disease 2019?

BACKGROUND: The level of angiotensin-converting enzyme 2 (ACE2) expression in different tissues is essential in the sensitivity, symptoms and consequences of COVID-19 infection. It seems that zinc is involved in the structure of the ACE2 enzyme has been identified; nonetheless, the relationship between ACE2 expression and zinc serum levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is still unclear. This study aimed to evaluate the expression of ACE2 in peripheral blood-derived immune cells of COVID-19 patients and its relationship with serum zinc levels. METHODS: Thirty healthy subjects and thirty patients with COVID-19 were enrolled in this study. The COVID-19 infection was confirmed by positive real-time polymerase chain reaction (RT-PCR) and radiological data. Peripheral blood samples were taken from healthy subjects and COVID-19 patients. Whole blood samples were also used to measure ACE2 gene expression by RT-PCR technique. The correlation matrix evaluated the relationship between ACE2 expression, serum zinc levels, and other related variables. RESULTS: The outcomes showed no considerable alteration in serum zinc levels between patients and the control group. Likewise, the ACE2 gene expression results showed a significant decrease in this receptor's expression in COVID-19 patients compared with the healthy subjects. A significant positive correlation was observed between serum zinc level and ACE2 gene expression in patients with COVID-19. CONCLUSION: The immune system seems to reduce the mRNA expression of the ACE2 in the peripheral blood leukocytes following SARS-CoV-2 infection. Moreover, zinc deficiency can make patients more susceptible to SARS-CoV-2 infection.

The relationship between serum levels of interleukin-2 and IL-8 with circulating microRNA-10b in patients with COVID-19.

BACKGROUND: The role of cytokine storm in the immunopathogenesis of coronavirus disease 2019 (COVID-19) has been implicated. OBJECTIVE: To determine the association of microRNA (miRNA)-10b and serum levels of IL-2 and IL-8 in patients with COVID-19. METHODS: Blood samples were obtained from 33 COVID-19 patients and 29 healthy subjects. After RNA extraction and cDNA synthesis, the transcript level of miR-10b was determined by Real-time PCR. In addition, the serum levels of IL-2 and IL-8 were measured in subjects using ELISA. RESULTS: The patient group comprised of 33 patients with COVID-19 (62.4 ± 3.7 years old), 13 (39%) males and 20 (61%) females. In the control group, 29 subjects (56.6 ± 1.6 years old), 9 (31%) males and 20 (69%) females, were included. The expression of miR-10b was significantly downregulated in the peripheral blood of COVID-19 patients in comparison to the healthy controls (fold change= 0.12, P< 0.0001). The levels of IL-2 (P< 0.001) and IL-8 (P< 0.001) were significantly increased in the serum samples of COVID-19 patients compared to the healthy subjects. The expression level of miR-10b was correlated significantly with the serum levels of IL-2 and IL-8 as well as with the age of patients, ESR and CRP levels. CONCLUSIONS: miR-10b is downregulated in the COVID-19 patients and might result in increased levels of IL-2 and IL-8, hence contributing to cytokine storm.

Predictors for the severe coronavirus disease 2019 (COVID-19) infection in patients with underlying liver disease: a retrospective analytical study in Iran.

Risk factors for clinical outcomes of COVID-19 pneumonia have not yet been well established in patients with underlying liver diseases. Our study aimed to describe the clinical characteristics and outcomes of COVID-19 infection among patients with underlying liver diseases and determine the risk factors for severe COVID-19 among them. In a retrospective analytical study, 1002 patients with confirmed COVID-19 pneumonia were divided into two groups: patients with and without underlying liver diseases. The admission period was from 5 March to 14 May 2020. The prevalence of underlying conditions, Demographic data, clinical parameters, laboratory data, and participants' outcomes were evaluated. Logistic regression was used to estimate the predictive factors. Eighty-one (8%) of patients had underlying liver diseases. The frequencies of gastrointestinal symptoms such as diarrhea and vomiting were significantly higher among patients with liver diseases (48% vs. 25% and 46.1% vs. 30% respectively, both P < 0.05). Moreover, ALT and AST were significantly higher among patients with liver diseases (54.5 ± 45.6 vs. 37.1 ± 28.4, P = 0.013 and 41.4 ± 27.2 vs. 29.2 ± 24.3, P = 0.028, respectively). Additionally, the mortality rate was significantly high in patients with liver disease (12.4% vs. 7%, P = 0.018). We also observed that the parameters such as neutrophil to leukocyte ratio [Odds Ratio Adjusted (ORAdj) 1.81, 95% CI 1.21-3.11, P = 0.011] and blood group A (ORAdj 1.59, 95% CI 1.15-2.11, P = 0.001) were associated with progression of symptoms of COVID-19. The presence of underlying liver diseases should be considered one of the poor prognostic factors for worse outcomes in patients with COVID-19.