The paradox of immunosuppressants and COVID-19

Cheng, Guang‐Shing; Evans, Scott E.

doi:10.1183/13993003.02828-2021

Cited by 10 publications

(14 citation statements)

References 16 publications

(25 reference statements)

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“…Its immunostimulant properties could also be beneficial to prevent subsequent opportunistic bacterial infections. Unlike glucocorticoids, NAC would seem to have a more favourable effect on modulating both the inflammatory and immune responses against infection [ 172 , 173 ]. Many of these properties exhibited by NAC could likely be ascribed to increased intracellular inorganic sulfate levels.…”

Section: Nac As a Therapeutic Agentmentioning

confidence: 99%

“…A significant percentage of patients in both the NAC and control group received dexamethasone and other medications, which could reduce the degree of HS sulfation and therefore attenuated the GL [ 3 , 198 ]. It is known that glucocorticoids may have intrinsic immunosuppressive drawbacks when applied at the wrong time, high dosages, and long term [ 3 , 172 , 173 , 199 , 200 ], while NAC is not immunosuppressive [ 159 ]. When higher concentration of IV NAC was given, better clinical outcomes could be expected.…”

Section: Treatment Recommendations For Covid-19mentioning

confidence: 99%

“…Steroids, aspirin, colchicine, acetaminophen, and nonsteroidal anti-inflammatory drugs appear to enhance viral replication and aggravate Ep and En dysfunction and the cytokine storm [ 3 , 19 , 172 , 173 , 198 , 199 , 204 ] through the depletion of inorganic sulfate for its metabolism [ 16 , 186 , 187 ]; [ 19 , 165 , 188 , 189 , 205 ]. These medications should therefore not be prescribed without a sulfur donor such as IV NAC or STS.…”

Section: Treatment Recommendations For Covid-19mentioning

confidence: 99%

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N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Preez

Aldous

Kruger

et al. 2022

Advances in Pharmacological and Pharmaceutical Sciences

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The airway epithelial glycocalyx plays an important role in preventing severe acute respiratory syndrome coronavirus 2 entry into the epithelial cells, while the endothelial glycocalyx contributes to vascular permeability and tone, as well as modulating immune, inflammatory, and coagulation responses. With ample evidence in the scientific literature that coronavirus disease 2019 (COVID-19) is related to epithelial and endothelial dysfunction, preserving the glycocalyx should be the main focus of any COVID-19 treatment protocol. The most studied functional unit of the glycocalyx is the glycosaminoglycan heparan sulfate, where the degree and position of the sulfate groups determine the biological activity. N-acetylcysteine (NAC) and other sulfur donors contribute to the inorganic sulfate pool, the rate-limiting molecule in sulfation. NAC is not only a precursor to glutathione but also converts to hydrogen sulfide, inorganic sulfate, taurine, Coenzyme A, and albumin. By optimising inorganic sulfate availability, and therefore sulfation, it is proposed that COVID-19 can be prevented or at least most of the symptoms attenuated. A comprehensive COVID-19 treatment protocol is needed to preserve the glycocalyx in both the prevention and treatment of COVID-19. The use of NAC at a dosage of 600 mg bid for the prevention of COVID-19 is proposed, but a higher dosage of NAC (1200 mg bid) should be administered upon the first onset of symptoms. In the severe to critically ill, it is advised that IV NAC should be administered immediately upon hospital admission, and in the late stage of the disease, IV sodium thiosulfate should be considered. Doxycycline as a protease inhibitor will prevent shedding and further degradation of the glycocalyx.

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Section: Nac As a Therapeutic Agentmentioning

confidence: 99%

Section: Treatment Recommendations For Covid-19mentioning

confidence: 99%

Section: Treatment Recommendations For Covid-19mentioning

confidence: 99%

See 1 more Smart Citation

N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Preez

Aldous

Kruger

et al. 2022

Advances in Pharmacological and Pharmaceutical Sciences

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“…An Australian study also found that immunosuppressed patients were not at significantly increased risk of COVID‐19 infection 22 . Furthermore, an overexuberant host response characterized by elevated interleukin‐6 (IL‐6) and other proinflammatory cytokines was associated with poor outcomes in severe COVID‐19 cases 23 …”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Choi,

Ai,

et al. 2024

Immunity Inflam & Disease

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IntroductionTo evaluate whether treated with immunosuppressants in neuromyelitis optica spectrum disorder (NMOSD) shows an effect on the severity and outcomes of COVID‐19 Omicron variant.MethodsThis is a substudy of a single‐center clinical trial involving human umbilical cord mesenchymal stem cells (hUC‐MSCs) in NMOSD patients. NMOSD patients with hUC‐MSCs treatment, NMOSD patients without hUC‐MSCs treatment, and matched healthy controls (HC) were included. Demographic information, NMOSD‐related clinical features, comorbidities, use of disease‐modifying therapy, COVID‐19 vaccination status, COVID‐19 clinical features, COVID‐19 clinical outcomes, and NMOSD‐related disease activity were obtained through online questionnaires or phone calls.ResultsThe majority of NMOSD patients received long‐term treatment with mycophenolate mofetil (68.8%) or azathioprine (22.9%), and 50% received oral glucocorticoid. During the epidemic, 97.4% of NMOSD patients infected with COVID‐19 had asymptomatic or mild forms, with only two patients (2.6%) requiring hospitalization. None of these patients required tracheal intubation or admission to the intensive care unit. Clinical symptoms were found to be more prevalent in HC groups. Additionally, the HC groups had higher fever‐recorded temperatures. NMOSD patients who received hUC‐MSCs treatment had shorter disease duration than patients who did not receive hUC‐MSCs treatment.DiscussionImmunosuppressant‐treated patients with NMOSD have a similar risk of COVID‐19 infection as the general population, but the disease duration is shorter and the clinical symptoms are less severe. Among our NMOSD patients who received hUC‐MSCs treatment, COVID‐19 outcomes were favorable, with no increased risk of severe COVID‐19. Prospective studies on immunotherapies are needed to help determine best treatment practices.

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“…Current clinical practice guidelines support continuation of immunosuppressive therapies in patients with chronic diseases who require them, with the exception of high-dose glucocorticoids, which were associated with worse COVID-19 outcomes. 67 , 68 A retrospective cohort study investigated whether patients undergoing immunosuppressive therapies for solid organ transplantations, cancers, or rheumatological disorders were at higher risk for mechanical ventilation or in-hospital death due to COVID-19 compared to non-immunosuppressed individuals. The authors found that only RTX negatively impacted COVID-19 outcomes.…”

Section: Reviewmentioning

confidence: 99%

Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability

Ciolfi¹,

Sernicola²,

Alaibac³

2022

PPA

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Anti-CD20 monoclonal antibody rituximab is an approved adjuvant treatment, in combination with oral corticosteroids, for patients with pemphigus vulgaris, a severe and potentially life-threatening autoimmune blistering skin disorder. Updated approaches to the management of pemphigus vulgaris support rituximab as a first-line adjuvant treatment to induce remission early in the course of disease; however, its feasibility in the clinical setting is often reduced by a series of limitations, including high cost of this biological drug, physician and patient concern for the risk of adverse reactions, and uncertainty regarding the optimum dosing and schedule of administration. The standard approved rituximab dosages, which are derived from lymphoma protocols, have been recognized to exceed the effective dose required for inducing B cell depletion, since the B cell burden in pemphigus vulgaris is much lower than in lymphoproliferative disorders. To overcome these limitations, recent research has investigated alternative regimens of rituximab, using lower doses of the drug. Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. Finally, low-dose regimens of rituximab were suggested to be favorable during the COVID-19 pandemic by providing a lesser degree of immune cell depletion while retaining a sufficient response. In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. Further evidence from rigorous clinical trials will be required to optimize lower-dose regimens of RTX and establish their position within the treatment scenario of pemphigus vulgaris.

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The paradox of immunosuppressants and COVID-19

Cited by 10 publications

References 16 publications

N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD

Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability

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