Convalescent plasma is ineffective for covid-19

Pathak, Elizabeth B

doi:10.1136/bmj.m4072

Cited by 41 publications

(31 citation statements)

References 17 publications

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“…In contrast, LL-37 can be produced synthetically with high purity and in unlimited quantities. Also, the use of antibodies from reconvalescent donors did not result in clinical benefits or in reduction in all-cause mortality 47,48 . Therefore, the use of vitamin D as an infection prophylaxis and the therapeutic administration of vitamin D for the treatment of COVID-19 patients, and the direct use of LL-37 by inhalation or systemic application could be good alternatives.…”

Section: Discussionmentioning

confidence: 99%

LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2In Vitro

Roth

Luetke

Meinberger

et al. 2020

Preprint

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Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen accountable for the coronavirus disease 2019 (COVID-19) pandemic. Viral entry via binding of the receptor binding domain (RBD) located within the S1 subunit of the SARS-CoV-2 Spike (S) protein to its target receptor angiotensin converting enzyme (ACE) 2 is a key step in cell infection. The efficient transition of the virus is linked to a unique protein called open reading frame (ORF) 8. As SARS-CoV-2 infections can develop into life threatening lower respiratory syndromes, effective therapy options are urgently needed. Several publications propose vitamin D treatment, although its mode of action against COVID-19 is not fully elucidated. It is speculated that vitamin D's beneficial effects are mediated by up regulating LL-37, a well known antimicrobial peptide with antiviral effects. Methods: Recombinantly expressed SARS-CoV-2 S protein, the extended S1 subunit (S1e), the S2 subunit (S2), the receptor binding domain (RBD), and ORF8 were used for surface plasmon resonance (SPR) studies to investigate LL-37's ability to bind to SARS-CoV-2 proteins and to localize its binding site within the S protein. Binding competition studies were conducted to confirm an inhibitory action of LL-37 on the attachment of SARS-CoV-2 S protein to its entry receptor ACE2. Results: We could show that LL-37 binds to SARS-CoV-2 S protein (LL-37/S-Strep KD = 407 nM, LL-37/S-His KD = 414 nM) with the same affinity, as SARS-CoV-2 binds to hACE2 (hACE2/S-Strep KD = 374 nM, hACE2/S-His KD = 368 nM). The binding is not restricted to the RBD of the S protein, but rather distributed along the entire length of the protein. Interaction between LL-37 and ORF8 was detected with a KD of 294 nM. Further, inhibition of the binding of S-Strep (IC50 = 735 nM), S1e (IC50 = 168 nM), and RBD (IC50 = 126 nM) to hACE2 by LL-37 was demonstrated. Conclusions: We have revealed a biochemical link between vitamin D, LL-37, and COVID-19 severity. SPR analysis demonstrated that LL-37 binds to SARS-CoV-2 S protein and inhibits binding to its receptor hACE2, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 that protects from SARS-CoV-2 infection, and the therapeutic administration of vitamin D for the treatment of COVID-19 patients. Further, our results provide evidence that the direct use of LL-37 by inhalation and systemic application may reduce the severity of COVID-19.

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Section: Discussionmentioning

confidence: 99%

LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2In Vitro

Roth

Luetke

Meinberger

et al. 2020

Preprint

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“…Although passive transfer of antibody to patients unable to make antibody is a logical strategy, the value of antibody infusion to patients with normal immune systems is a matter of discussion. In COVID-19 patients, a randomized control groups trial recently failed to demonstrate efficacy [22,23]. However, the administration of convalescent plasma may be a useful approach for the treatment of patients whose immune systems have been compromised by both an underlying disease such as IEI, or secondary to B cell depleting therapies, such as anti-CD20 monoclonal antibody therapy [24,25].…”

Section: Convalescent Plasmamentioning

confidence: 99%

Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic

Quinti

Mezzaroma

Milito

2021

Expert Review of Clinical Immunology

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“…The role of convalescent plasma has been investigated in the PLACID trial 60 , 61 in patients admitted to hospital with moderate COVID-19: although a statistically significant higher rate of conversion to a negative result for SARS-CoV-2 RNA occurred on day 7 among patients in the intervention arm, no clinical benefit was associated with the use of convalescent plasma.…”

Section: Management Of Kidney Injury During Sars-cov-2 Infectionmentioning

confidence: 99%

Renal Involvement in COVID-19: A Review of the Literature

Migliaccio¹,

Mauro²,

Ricciolino³

et al. 2021

IDR

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Kidney injury may be a severe complication of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to worsen the prognosis. Various pathophysiological mechanisms can contribute to organ damage and impair renal function, proving the complexity of the virus activity and the resulting immunity response. We summarized the evidence of the literature on the prevalence of kidney involvement, on the pathogenic pathways and on its management.

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Convalescent plasma is ineffective for covid-19

Abstract: Convalescent plasma generated great enthusiasm in the earliest days of the coronavirus disease 2019 (covid-19) pandemic because of a plausible mechanism of action, 1 its 100 year history of use in the treatment of other infectious diseases, 2 and rapid availability from voluntary donors. 3

Cited by 41 publications

References 17 publications

LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2In Vitro

LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2In Vitro

Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic

Renal Involvement in COVID-19: A Review of the Literature

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