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

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Abstract

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-1β, 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-1β, 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-1β 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-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.

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Most cited references 32

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Qiurong Ruan, Kun Yang, Wenxia Wang … (2020)

Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths [1]. Many infected patients, however, presented mild flu-like symptoms and quickly recover [2]. To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes. Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student’s t test or the Mann–Whitney–Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher’s exact test. The distribution of the enrolled patients’ age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups (Fig. 1b and Supplementary Table 1). Fig. 1 a Age distribution of patients with confirmed COVID-19; b key laboratory parameters for the outcomes of patients with confirmed COVID-19; c interval from onset of symptom to death of patients with confirmed COVID-19; d summary of the cause of death of 68 died patients with confirmed COVID-19 The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness [3], our results should alert physicians to pay attention not only to the symptoms of respiratory dysfunction but also the symptoms of cardiac injury. Further, large-scale studies and the studies on autopsy are needed to confirm our analysis. In conclusion, predictors of a fatal outcome in COVID-19 cases included age, the presence of underlying diseases, the presence of secondary infection and elevated inflammatory indicators in the blood. The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 38 kb)

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The trinity of COVID-19: immunity, inflammation and intervention

Matthew Tay, Chek Meng Poh, Laurent Rénia … (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

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Author and article information

Journal

Journal ID (nlm-ta): Int Immunopharmacol

Journal ID (iso-abbrev): Int Immunopharmacol

Title: International Immunopharmacology

Publisher: Published by Elsevier B.V.

ISSN (Print): 1567-5769

ISSN (Electronic): 1878-1705

Publication date PMC-release: 20 October 2020

Publication date (Print): December 2020

Publication date (Electronic): 20 October 2020

Volume: 89

Page: 107088

Affiliations

[a ]Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran

[b ]Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

[c ]Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

[d ]Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

[e ]Department of propaedeutics of dental diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

[f ]Department of Family Medicine, Yassawi International Kazakh-Turkish University Hospital, Turkistan, Kazakhstan

[g ]Department of Surgery, Mousavi Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

[h ]Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

[i ]Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran

Article

Publisher Item ID: S1567-5769(20)32189-5 Publisher ID: 107088

DOI: 10.1016/j.intimp.2020.107088

PMC ID: 7574843

PubMed ID: 33129099

SO-VID: ed57b971-f19e-4596-9fe2-9bf59961941e

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

History

Date received : 30 June 2020

Date revision received : 8 October 2020

Date accepted : 8 October 2020

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

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Abstract

Background

Method

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Conclusion

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Novel Coronavirus Disease COVID-19

Most cited references 32

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

The trinity of COVID-19: immunity, inflammation and intervention

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Cited by 105

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