Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!

Nguyen, Andrew V.; Habiballah, Saddiq; Platt, Craig D.; Geha, Raif S.; Chou, Janet; McDonald, Douglas R.

doi:10.1016/j.clim.2020.108459

Cited by 111 publications

(110 citation statements)

References 22 publications

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“…IVIG has been used to provide immunity to viral infections [78], including SARS, although the benefits of the treatment were inconclusive and some cases of thromboembolic complications were reported [79,80]. IVIG is different from hyperimmune globulin from convalescent plasma, wherein the plasma is prepared from the plasma of donors with high antibody titers to specific pathogens [81]. The mechanisms of action of IVIG are complex, and several mechanisms might account for its therapeutic benefit [82].…”

Section: Human Immunoglobulinmentioning

confidence: 99%

Pharmaco-Immunomodulatory Therapy in COVID-19

Rizk

Kalantar-Zadeh

Mehra

et al. 2020

Drugs

247

244

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The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colonystimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms. Key Points COVID-19 is a syndrome of viral replication and a host inflammatory response. Tackling the immune response may be as important as addressing viral replication. Specific and non-specific immune modulators have the potential to inhibit cytokines and quell the cytokine storm.

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Section: Human Immunoglobulinmentioning

confidence: 99%

Pharmaco-Immunomodulatory Therapy in COVID-19

Rizk

Kalantar-Zadeh

Mehra

et al. 2020

Drugs

247

244

View full text Add to dashboard Cite

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“…Nevertheless, IVIG remains widely used for patients with sepsis, despite a lack of strong evidence supporting this application (26)(27)(28). The use of high dose of IVIG is effective in the treatment of COVID-19, possibly through immune modulation, saturating Fc receptor, and reducing antibody-dependent enhancement of in ammatory response (29).…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multi-center study

Liu

Chen

et al. 2020

Preprint

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Background: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcomes remain unclear. This study evaluated the effectiveness of IVIG treatment for severe COVID-19.Methods: This retrospective multi-center study evaluated 28-day mortality and time for SARS-CoV-2 RNA clearance in severe COVID-19 patients with or without IVIG treatment. Propensity score matching was used to control confounding factors. Logistic regression and competing risk analyses were performed.Results: The study included 850 patients (421 patients received IVIG). No significant differences in 28-day mortality or time for SARS-CoV-2 RNA clearance were observed (p=0.357 and p=0.123, respectively). High-dose of IVIG treatment (>10 g/day) (n=27) was associated with decreased 28-day mortality (OR: 0.33, 95% CI: 0.14–0.77; p=0.011). The IVIG group had prolonged median hospitalization, less shock, and higher incidences of acute respiratory distress syndrome, myocardial injury. Furthermore, IVIG-treated patients were more likely to require non-invasive mechanical ventilation and less likely to require invasive mechanical ventilation.Conclusions: IVIG treatment for severe COVID-19 patients was not associated with significant improvements in 28-day mortality or time for SARS-CoV-2 RNA clearance. However, some improvements in 28-day survival were observed for high-dose IVIG treatment (>10 g/day).

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“…[8] Treatment of hyperinflammation and immunosuppression are highly recommended to address the immediate need to reduce mortality. [2] Current immunosuppression options include steroids, [9] intravenous immunoglobulin, [10] selective cytokine blockade (e.g., anakinra [11] or tocilizumab [12] ), and Janus kinase inhibition. [13] In light of the findings that elevated levels of reactive oxygen species (ROS) is strongly correlated with inflammation, [14] oxidative injury, [15] as well as viral infection and replication, [16][17][18] we speculate that regu lating the ROS level in COVID-19 patients could be effective for the treatment of hyperinflammation, protection of tissues from oxidative injury, and repression of viral replication.…”

Section: Doi: 101002/adma202004901mentioning

confidence: 99%

An Antioxidant Enzyme Therapeutic for COVID‐19

et al. 2020

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The COVID‐19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. Herein it is a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process, is reported. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS‐CoV‐2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID‐19.

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Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!

Abstract: Immunoglobulins, including intravenous immunoglobulin and convalescent plasma, have potential uses and limitations in the treatment of COVID-19 infection.

Cited by 111 publications

References 22 publications

Pharmaco-Immunomodulatory Therapy in COVID-19

Pharmaco-Immunomodulatory Therapy in COVID-19

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multi-center study

An Antioxidant Enzyme Therapeutic for COVID‐19

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