Modulating the host immune response to fight against COVID-19: Where are we in 2021?

Hertanto, Decsa Medika; Sutanto, Henry; Wiratama, Bayu Satria; Wungu, Citrawati Dyah Kencono

doi:10.1080/21505594.2021.1943275

Cited by 9 publications

(7 citation statements)

References 35 publications

(39 reference statements)

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“…The TLR4 pathway can produce IL6, a critical cytokine associated with cytokine storm, suggesting that TLR4 participates in SARS-CoV-2 invasion. NLRP3 inflammatory bodies composed of apoptosis-associated speck-like protein, caspase-1, and oligomeric NLRP3 contribute to severe COVID-19, and inflammatory bodies might be related to severe cytokine storms, resulting in ARDS and even death 90 , 91 . Anti-inflammatory and NLRP3 inflammatory body inhibitors could be potential therapeutic drugs for COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Potential Genes Associated with COVID-19 and Comorbidity

Feng¹,

Song²,

Guo³

et al. 2022

Int. J. Med. Sci.

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Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.

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Section: Discussionmentioning

confidence: 99%

Potential Genes Associated with COVID-19 and Comorbidity

Feng¹,

Song²,

Guo³

et al. 2022

Int. J. Med. Sci.

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“…In more severely ill patients, lymphopenia may be present due to exhaustion, specifically, of cytotoxic lymphocytes [16,17]. The reported systemic hyperinflammation in patients, likely due to the presence of pro-inflammatory cytokines, has been associated with vascular leakage, multiorgan damage, and death [18]. Such dysregulation of the immune response may underlie the emergence of the MIS-C presentation.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Characteristics Associated with COVID-19 in Children with Typical Presentation and with Multisystem Inflammatory Syndrome

Kornitzer

Johnson

Yang

et al. 2021

IJERPH

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Setting off a global pandemic, coronavirus disease 2019 (COVID-19) has been marked by a heterogeneous clinical presentation that runs the gamut from asymptomatic to severe and fatal. Although less lethal in children than adults, COVID-19 has nonetheless afflicted the pediatric population. This systematic review used clinical information from published literature to assess the spectrum of COVID-19 presentation in children, with special emphasis on characteristics associated with multisystem inflammatory syndrome (MIS-C). An electronic literature search for English and Chinese language articles in COVIDSeer, MEDLINE, and PubMed from 1 January 2020 through 1 March 2021 returned 579 records, of which 54 were included for full evaluation. Out of the total 4811 patients, 543 (11.29%) exhibited MIS-C. The most common symptoms across all children were fever and sore throat. Children presenting with MIS-C were less likely to exhibit sore throat and respiratory symptoms (i.e., cough, shortness of breath) compared to children without MIS-C. Inflammatory (e.g., rash, fever, and weakness) and gastrointestinal (e.g., nausea/vomiting and diarrhea) symptoms were present to a greater extent in children with both COVID-19 and MIS-C, suggesting that children testing positive for COVID-19 and exhibiting such symptoms should be evaluated for MIS-C.

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“…Therefore, we cannot rule out a potential benefit of anakinra or baricitinib added to steroids based on the pathophysiology described in patients with COVID-19 [3]. Finally, complement system inhibition is also a potential therapeutic target for COVID-19 [8]. In this study, immunomodulatory drugs were used independently, but it will be interesting to investigate the potential role of the combination or sequential use of IL and JAK inhibitors in COVID-19.…”

Section: Discussionmentioning

confidence: 98%

“…Several immunomodulatory drugs have also been considered in the treatment of COVID-19, including recombinant human interleukin (IL) inhibitors [7], such as tocilizumab and anakinra, or the Janus kinase (JAK) inhibitor baricitinib [8]. An agent blocking the IL-6 receptor, tocilizumab, was one of the first immunomodulatory therapies to be proposed, given the fact that higher IL-6 concentrations have been associated with worse outcomes in patients with COVID-19 [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Anakinra versus Baricitinib: Different Strategies for Patients Hospitalized with COVID-19

García‐García

Pérez-Quintana²,

Ramos-Giraldez

et al. 2021

JCM

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Background: Immunomodulatory drugs have been used in patients with severe COVID-19. The objective of this study was to evaluate the effects of two different strategies, based either on an interleukin-1 inhibitor, anakinra, or on a JAK inhibitor, such as baricitinib, on the survival of patients hospitalized with COVID-19 pneumonia. Methods: Individuals admitted to two hospitals because of COVID-19 were included if they fulfilled the clinical, radiological, and laboratory criteria for moderate-to-severe disease. Patients were classified according to the first immunomodulatory drug prescribed: anakinra or baricitinib. All subjects were concomitantly treated with corticosteroids, in addition to standard care. The main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital death. Statistical analysis included propensity score matching and Cox regression model. Results: The study subjects included 125 and 217 individuals in the anakinra and baricitinib groups, respectively. IMV was required in 13 (10.4%) and 10 (4.6%) patients, respectively (p = 0.039). During this period, 22 (17.6%) and 36 (16.6%) individuals died in both groups (p = 0.811). Older age, low functional status, high comorbidity, need for IMV, elevated lactate dehydrogenase, and use of a high flow of oxygen at initially were found to be associated with worse clinical outcomes. No differences according to the immunomodulatory therapy used were observed. For most of the deceased individuals, early interruption of anakinra or baricitinib had occurred at the time of their admission to the intensive care unit. Conclusions: Similar mortality is observed in patients treated with anakinra or baricitinib plus corticosteroids.

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Modulating the host immune response to fight against COVID-19: Where are we in 2021?

Cited by 9 publications

References 35 publications

Potential Genes Associated with COVID-19 and Comorbidity

Potential Genes Associated with COVID-19 and Comorbidity

A Systematic Review of Characteristics Associated with COVID-19 in Children with Typical Presentation and with Multisystem Inflammatory Syndrome

Anakinra versus Baricitinib: Different Strategies for Patients Hospitalized with COVID-19

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