Harnessing the Immune System to Overcome Cytokine Storm and Reduce Viral Load in COVID-19: A Review of the Phases of Illness and Therapeutic Agents

Khadke, Sumanth; Ahmed, Nayla; Ahmed, Nausheen; Ratts, MD/PhD Ryan; Raju, Shine; MD/PhD, Molly Gallogly,; Lima, Marcos de; Sohail, M. Rizwan

doi:10.2139/ssrn.3603857

Cited by 24 publications

(34 citation statements)

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“…Therefore, TLR4 could also be involved in the pathogenesis of COVID-19. 21,22 An in silico study has also revealed a close relationship between bat SARS-CoV and SARS-CoV-2 (based on the spike protein and ACE2) and found that SARS-CoV-2 spike protein binds with TLR1, 4, and 6, with a higher affinity for TLR4. TLR4 antagonist could be administered for treating COVID-19 patients.…”

Section: Tlrs In Sars-cov and Mers-covmentioning

confidence: 99%

“…27 However, other studies on SARS-CoV-2 have revealed the pathologic role of TLR4 in excessive inflammation in COVID-19 patients as it leads to NETosis and activation of inflammasome, as mentioned before. 20,22,28 TLR agonists could also be used as prophylactic drugs for SARS-CoV-2. Proud et al 29 revealed that prophylactic administration of TLR2/6 agonist reduces SARS-CoV-2 transmission and provides protection against COVID-19.…”

Section: Tlrs In Sars-cov-2mentioning

confidence: 99%

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Role of Toll‐like receptors in the pathogenesis of COVID‐19

Khanmohammadi

Rezaei

2021

Journal of Medical Virology

299

262

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Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a pandemic since March 2020. The exact pathogenesis of SARS-CoV-2 and the role of each component of the innate and adaptive immune system is still unknown. However, available data from other coronavirus families, such as SARS-CoV and the Middle East respiratory syndrome and also new findings could be useful for a better understanding of SARS-CoV-2. Toll-like receptors (TLR) play an important role in recognition of viral particles and activation of the innate immune system. Activation of TLR pathways leads to secretion of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α, as well as type 1 interferon. Different TLRs, like TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 are potentially important in COVID-19 infection. It is also worth mentioning that we should bear in mind both the beneficial and harmful effects of TLR in confronting COVID-19 infection. TLRs could be a potential target in controlling the infection in the early stages of disease and production of vaccine against SARS-CoV-2.

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Section: Tlrs In Sars-cov and Mers-covmentioning

confidence: 99%

Section: Tlrs In Sars-cov-2mentioning

confidence: 99%

Role of Toll‐like receptors in the pathogenesis of COVID‐19

Khanmohammadi

Rezaei

2021

Journal of Medical Virology

299

262

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“…5 Mekanisme inflamasi pada COVID-19 paralel dengan mekanisme kerja kolkisin yang menunjukkan titik intervensi potensial yang dapat mencegah perkembangan dari fase 2 (aktivasi inflamasi) ke fase 3 (hiperinflamasi). 5,32,33 Kemampuan kolkisin mengikat dimer tubulin bebas yang memblok polimerisasi mikrotubulus dipercaya sebagai efek yang dapat meredam aktivitas sel peradangan dan pelepasan sitokin, kolkisin juga dapat mengontrol aktivitas sel darah putih dalam melepaskan sitokin dan pyrogen. 30,31 Efek kolkisin dapat maksimal saat digunakan pada awal proses penyakit.…”

Section: Pembahasanunclassified

“…25,29 Kolkisin berbeda dengan glukokortikosteroid seperti dexamethanose karena kolkisin tidak memiliki dampak imunosupresif intrinsik yang dapat meningkatkan risiko infeksi sekunder pada pasien. 5,16,32,33,36 Terapi biologi pada infeksi SARS-CoV-19 mentargetkan jalur spesifik seperti anakinra dengan target IL1-beta dan tocilizumab pada target IL6. Namun kolkisin memiliki efek multiple yang tidak spesifik pada target tunggal tertentu.…”

Section: Pembahasanunclassified

Kolkisin Sebagai Terapi Adjuvan Pada Coronavirus Disease

Hidayat¹,

Raharjo

2021

JKK

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Beragam manifestasi klinis, patogenesis yang masih belum pasti, dan belum ditemukannya obat yang efektif untuk penanganan Coronavirus Disease (COVID-19) mendorong penggunaan berbagai obat off-label sebagai upaya penyembuhan pasien. Obat anti peradangan dan imunomodulator banyak dipakai dalam terapi terutama untuk kasus berat dan kritis. Kolkisin yang dikenal sebagai obat gout diuji coba sebagai alternatif pengobatan COVID-19. Namun penggunaan obat ini sebagai pilihan terapi pada COVID-19 masih jarang. Tinjauan ini bertujuan untuk mengetahui dampak penggunaan kolkisin sebagai terapi adjuvan COVID-19. Tinjauan literatur ini dilakukan dengan mencari jurnal yang telah dipublikasi secara bebas di berbagai jurnal kedokteran internasional dengan kata kunci "colchicine AND COVID-19 journal" dan diperoleh sebanyak 10 jurnal yang secara spesifik membahas mengenai kolkisin dan COVID-19. Penelitian yang ada menunjukkan bahwa Kolkisin memiliki dampak positif terhadap pengobatan COVID-19. Kolkisin memiliki efek anti inflamasi multipel yang tidak spesifik pada target tunggal tertentu dan tidak bersifat imunosupresif. Sifat immunomodulator, anti inflamasi dan antiviral menjadi dasar penggunaan kolkisin sebagai terapi adjuvan COVID-19. Kolkisin terbukti dapat mempercepat waktu perbaikan klinis pasien, menurunkan angka kematian, kebutuhan rawat inap, dan lama rawat pasien COVID-19. Sedangkan efek antitrombosis kolkisin pada COVID-19 masih memerlukan penelitian lebih lanjut. Kolkisin perlu diberikan secara berhati-hati terkait efeknya pada gastrointestinal dan perlunya penyesuaian pada gangguan ginjal. Penggunaan kolkisin pada pasien COVID-19 menjadi alternatif terapi potensial karena relatif aman, murah, tersedia banyak, dan penggunaan secara peroral. Dengan hasil tersebut diatas, kolkisin dapat dipertimbangkan sebagai bagian dari usaha penyembuhan pasien COVID-19.

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“…In early 2020, a new strain of coronavirus called SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), more commonly known as causing the Covid-19 disease, gave rise to a global pandemic (1). Starting from an epidemic outbreak in Wuhan (China), the virus quickly spread westwards towards Europe and the USA (2) with serious health and socio-economic consequences worldwide (3). SARS-CoV-2 exhibits a high propensity for infectious spread throughout populations (2).…”

Section: Introductionmentioning

confidence: 99%

Ultra-rapid on-site detection of SARS-CoV-2 infection using simple ATR-FTIR spectroscopy and analysis algorithm: high sensitivity and specificity

Baraúna

Singh²,

Barbosa

et al. 2020

Preprint

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There is an urgent need for ultra-rapid testing regimens to detect the SARS-CoV-2 [Severe Acute Respiratory Syndrome Coronavirus 2] virus infections in real-time within seconds to stop its spread. Current testing approaches for this RNA virus focus primarily on diagnosis by RT-qPCR, which is time-consuming, costly, often inaccurate and impractical for general population rollout due to the need for laboratory processing. The latency until the test result arrives with the patient has led to further virus spread. Furthermore, latest antigen rapid tests still require 15 to 30 min processing time and are challenging to handle. Despite increased PCR-test and antigen-test efforts the pandemic has entered the worldwide second stage. Herein, we applied a superfast reagent-free and non-destructive approach of attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy with subsequent chemometric analysis to the interrogation of virus-infected samples. Contrived samples with inactivated gamma-irradiated Covid-19 virus particles at levels down to 1582 copies/ml generated infrared (IR) spectra with good signal-to-noise ratio. Predominant virus spectral peaks are associated with nucleic acid bands, including RNA. At low copy numbers, the presence of virus particle was found to be capable of modifying the IR spectral signature of saliva, again with discriminating wavenumbers primarily associated with RNA. Discrimination was also achievable following ATR-FTIR spectral analysis of swabs immersed in saliva variously spiked with virus. Following on, we nested our test system in a clinical setting wherein participants were recruited to provide demographic details, symptoms, parallel RT-qPCR testing and the acquisition of pharyngeal swabs for ATR-FTIR spectral analysis. Initial categorisation of swab samples into negative versus positive Covid-19 infection was based on symptoms and PCR results. Following training and validation of a genetic algorithm-linear discriminant analysis (GA-LDA) algorithm, a blind sensitivity of 95% and specificity of 89% was achieved. This prompt approach generates results within two minutes and is applicable in areas with increased people traffic that require sudden test results such as airports, events or gate controls.

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Harnessing the Immune System to Overcome Cytokine Storm and Reduce Viral Load in COVID-19: A Review of the Phases of Illness and Therapeutic Agents

Cited by 24 publications

References 0 publications

Role of Toll‐like receptors in the pathogenesis of COVID‐19

Role of Toll‐like receptors in the pathogenesis of COVID‐19

Kolkisin Sebagai Terapi Adjuvan Pada Coronavirus Disease

Ultra-rapid on-site detection of SARS-CoV-2 infection using simple ATR-FTIR spectroscopy and analysis algorithm: high sensitivity and specificity

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