Interleukin-6 blocking agents for treating COVID-19: a living systematic review

Ghosn, Lina; Assi, Rouba; Evrenoglou, Theodoros; Buckley, Brian S; Probyn, Katrin; Davidson, Mauricia; Graña, Carolina; Bonnet, H; Jarde, Alexander; Ávila, Camila; Nejstgaard, Camilla Hansen; Menon, Sonia; Ferrand, G; Kapp, Philipp; Breuer, Claudia; Schmucker, Christine; Sguassero, Yanina; Nguyen, Van Thu; Devane, Declan; Meerpohl, Joerg J; Rada, Gabriel; Hróbjartsson, Asbjørn; Grasselli, Giacomo; Tovey, David; Ravaud, Philippe; Chaimani, Anna; Boutron, Isabelle

doi:10.1002/14651858.cd013881.pub2

Cited by 11 publications

(8 citation statements)

References 103 publications

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“…The COVID-19 patients included in the present study, who were suffering from cytokine storm with signs and symptoms of the disease, were hospitalized for varying durations (8-45 days). Being in such a critical condition, the patients were administered various therapeutic agents to combat the disease and its signs and symptoms, since a definitive cure for COVID-19 is not available [8][9][10][11][12]. However, not all the drugs were COVID-19-specific, as the patients were suffering from comorbidities, which can be characterized as a multimorbidity condition (Table 1), which demands additional medications.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, the cytokine storm contributes to systemic deterioration and toxicity, disrupting the tricarboxylic acid cycle in various organ systems of COVID-19 patients [6,7]. The deterioration of COVID-19 cases involved with cytokine storm increases the demand for multiple medications and subjects the patients to polypharmacy, which might worsen the situation even more and potentially induce drug-drug interactions [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…This is especially true in the elderly and hospitalized COVID-19 patients needing long-term care and medications that eventually result in multiple drug therapy [18,19,21]. While polypharmacy has been documented in severe cases of COVID-19 [20][21][22], there is scarce information on its incidence among patients who suffer from the additional burden of cytokine storm, which requires even more medications [10,11]. The purpose of the present study was to assess the incidence of polypharmacy and in silico prediction of potential body proteins targeted by these drugs in hospitalized COVID-19 patients with concomitant cytokine storm in the city of Duhok, Kurdistan Region, Iraq.…”

Section: Introductionmentioning

confidence: 99%

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Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm

Raouf,

Mohammad,

Merza

2023

Cureus

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Background and objectivePolypharmacy is prevalent in coronavirus disease 2019 patients with severe disease. However, information on polypharmacy among COVID-19 patients who also suffer from cytokine storm is scarce. In light of this, the purpose of the present study was to assess the incidence of polypharmacy and in silico prediction of potential body proteins targeted by these drugs among hospitalized COVID-19 patients who were identified to have the additional burden of cytokine storm in the city of Duhok, Kurdistan Region, Iraq. MethodsThis was a cross-sectional observational study conducted from June 2021 to April 2022; the phenomena of major polypharmacy (six to nine medications) and excessive polypharmacy (≥10 medications) were documented among 33 (15 males and 18 females) COVID-19 patients with cytokine storm during their hospital stay (8-45 days) in Duhok, Kurdistan Region, Iraq. The SwissTargetPrediction program was utilized in silico to predict and identify human body proteins that could be potentially targeted by selected medications involved in polypharmacy. ResultsAll patients had tested positive for COVID-19 via PCR testing, and they showed different signs and symptoms of the disease. None of the patients recovered and all of them deceased. All 33 patients received many therapeutic agents that ranged in number from eight to 20/patient during their hospital stay. The mean number of medications was 15 ± 3. We identified 2/33 (6%) patients with major polypharmacy (eight and nine) and 31/33 (94%) with excessive polypharmacy (15.5 ± 2.7). The total number of medications identified in polypharmacy was 37, excluding vitamins, minerals, and intravenous solutions. The frequency of medications administered was as follows: antibiotics (67, 13.7%), mucolytic agents (56, 11.5%), corticosteroids (54, 11%), anticoagulants (48, 9.8%), antiviral agents (41, 8.4%), antihypertensive agents (32, 6.5%), analgesics (28, 5.7%), antifungal drugs (27, 5.5%), antidiabetics (26, 5.3%), and other medications (2-19, 0.41-3.9%). Using the SwissTargetPrediction program, various drugs including antiviral agents involved in polypharmacy were found to target, in silico, body proteins at a prediction percentage that ranged from 6.7% to 40%. ConclusionsMajor and extensive polypharmacy conditions were identified in hospitalized COVID-19 patients suffering from cytokine storm. The severity of COVID-19 with cytokine storm, comorbidities, and hospitalization were key factors associated with polypharmacy in the patients. The SwissTargetPrediction web server is useful for predicting in silico potential human body protein targets that could possibly be sources of additional information on the adverse/toxic effects of polypharmacy medications administered concurrently. Further research in current medication protocols prescribed for advanced COVID-19 illness with cytokine storm is warranted to gain deeper insights into the topic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm

Raouf,

Mohammad,

Merza

2023

Cureus

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“…In the meta-analysis of 18 RCTs including more than 7000 patients with severe COVID-19 the majority of whom were already on corticosteroids, compared to placebo/standard care, IL-6 inhibitors were shown to be associated with decreased all-cause mortality rate at day 28 with an average OR of 0.78 (95% CrI=0.65-0.94) and relative risk of 0.88, (95% CI=0.81-0.94) for tocilizumab; and 0.91 (95% CrI=0.60-1.40) for sarilumab. Interleukin (IL)-6 receptor antagonists also had a greater than 99.9% probability of improving 6-month survival (adjusted HR [aHR]= 0.74, 95% CrI=0.61-0.90) ( 107 , 108 ). Besides rreducing mortality during the acute phase of infection, tocilizumab also improved survival six months after acute COVID-19 ( 109 ).…”

Section: Anti-cytokine Agentsmentioning

confidence: 99%

COVID-19: An Update on Epidemiology, Prevention and Treatment, September-2023

Simsek-Yavuz

2023

Infect Dis Clin Microbiol

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After a downward trend for more than 12 months, the incidence of COVID-19 has increased in the last months. Although COVID-19 is not as frequent as in the first years of the pandemic, case numbers are still very high, and it causes a significant number of deaths. COVID-19 is not seen with a predictable frequency, at least two times more deadly than the flu, continues as an epidemic, and has not reached the endemic level yet. Currently, the Omicron strains EG.5 and XBB.1.16 are dominant worldwide. Although BA.2.86 and FLip variants, including FL.1.5.1 are not widespread at the moment, both were shown to be highly immune-evasive and require close monitoring. Prevention of COVID-19 relies on vaccinations, surveillance, proper ventilation of enclosed spaces, isolation of patients, and mask usage. Currently, monovalent COVID-19 vaccines, including XBB.1.5 Omicron SARS-CoV-2, are recommended for both primary and booster vaccinations against COVID-19. Monovalent vaccines, including only original SARS-CoV-2 strain, and bivalent vaccines, including original virus plus BA4/5 variant, are no longer recommended against COVID-19. Booster vaccination with XBB.1.5 containing vaccine should be prioritized for patients at high risk for severe COVID-19. Bacillus Calmette–Guérin (BCG) vaccination does not seem to be effective in preventing COVID-19. At the current phase of the pandemic, nirmatrelvir/ritonavir, remdesivir, molnupiravir, sotrovimab (for patients from XBB.1.5 variant dominant settings), and convalescent plasma can be considered for the treatment of high-risk early-stage outpatients with COVID-19, while hospitalized patients with more severe disease can be treated with dexamethasone, anti cytokines including tocilizumab, sarilumab, baricitinib, and tofacitinib and antithrombotic agents including enoxaparin. Remdesivir oral analogues and ensitrelvir fumarate are promising agents for treating acute COVID-19, which are in phase trials now; however, ivermectin, fluvoxamine, and metformin were shown to be ineffective.

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“…Immunotherapy-related agents, such as glucocorticoids and anti-interleukin-6 (IL-6) receptor antibodies, have effectively modulated the immune response and reduced excessive inflammation in these patients [21]. These treatments have demonstrated promising results in reducing mortality among individuals affected by the disease [22][23][24][25]. However, it is important to consider the potential risk of secondary infections associated with these therapies [26,27].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells in the Treatment of COVID-19

Guo,

Wu,

Chen

et al. 2023

IJMS

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Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.

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Interleukin-6 blocking agents for treating COVID-19: a living systematic review

Abstract: Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

Cited by 11 publications

References 103 publications

Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm

Polypharmacy and the In Silico Prediction of Potential Body Proteins Targeted by These Drugs Among Hospitalized COVID-19 Patients With Cytokine Storm

COVID-19: An Update on Epidemiology, Prevention and Treatment, September-2023

Mesenchymal Stem Cells in the Treatment of COVID-19

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