Hemin, erythropoietin and antithrombotics to treat Covid-19

Abrahams, Lianne

doi:10.31219/osf.io/fwxd5

Cited by 1 publication

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“…Thromboprophylaxis is routine care for hospitalised Covid-19 patients at risk of venous thromboembolism in the UK R14 , and is an element of standard care in other nations, although not all. Vote-counting results of previous literature review 2 suggest the subtype of antithrombotic most strongly associated with mortality reduction was anticoagulant (64% in favor), followed by aspirin (50% in favor), with antiplatelets as the least associated (25% in favor). It was not possible to comment on heparin, since only one study investigated heparin specifically.…”

Section: Introductionmentioning

confidence: 91%

“…Treatment protocols for Covid-19 remain suboptimal, although a number of recent studies intimate pathophysiology of the disease. Porphyrin dysmetabolism, thrombotic tendency and erythropoietic distress are three hallmarks of Covid-19 hematology 1,2 . Rationally, three corresponding types of intervention warrant further investigation: antiporphyrics, antithrombotics and erythropoiesis stimulating agents.…”

Section: Introductionmentioning

confidence: 99%

“…Rationally, three corresponding types of intervention warrant further investigation: antiporphyrics, antithrombotics and erythropoiesis stimulating agents. 2 The reader is invited to consult Abrahams 2022a 2 for an in-depth rationale relating to each of the three proposed interventions.…”

Section: Introductionmentioning

confidence: 99%

“…The gold standard test for an attack of acute porphyria is urinalysis of ALA and PBG levels; a Covid-19 clinical trial that has been designed 7 but not yet conducted. Besides, Upchurch's 6 patient was treated successfully with hemin and givosiran, two interventions suggested for investigation by the current author 2 and the subject of this meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

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Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis

Abrahams¹

2022

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Aims: Covid-19 hematology is hallmarked by porphyrin dysmetabolism, altered hemostasis and erythropoietic distress. We hypothesize that antiporphyrics, antithrombotics and erythropoiesis stimulating agents (ESAs) may prove beneficial in the treatment of severe Covid-19. The objective of the current study was to systematically review and meta-analyse the mortality risk profile of hospitalized Covid-19 patients, when treated with each of the three interventions of interest - versus placebo, standard of care or non-intervention.Methods: Eligible studies were identified from: biorxiv and medrxiv, clinical trials govR4, covid19 trials tracker netR5, DISCOVERR2 (Ebsco), ICTRPR7, PubMedR1 and Google ScholarR3 during search period 27 May-07 June 2022. Risk of bias was assessed with SIGN, NIH and JBI checklists and results quantitatively synthesised for antiporphyrics plus antithrombotics studies. Quantitative synthesis was performed in RevMan 5.4R9 with random effects model meta-analysis. Publication bias was assessed in R by funnel plot, Egger’s regression and trimfill analysis (metafor).Results: Number and type of studies included was 6 RCTs for antiporphyrics, 16 cohort for antithrombotics, and 3 case report/series for ESAs. Both unadjusted and adjusted analyses suggested that hydroxychloroquine treatment was not significantly associated with mortality risk in hospitalised Covid-19 patients (RR 0.95 [0.71, 1.29], P=0.76; aHR 0.78 [0.51, 1.22], P=0.28). Interestingly, the direction of effect shifted further towards favoring intervention when only high quality studies were included in the analysis (unadjusted RR 0.80 [0.42, 1.55]) compared with low quality studies (unadjusted RR 1.59 [0.71, 3.53]) although neither were statistically significant (P=0.51 and P=0.26, respectively). Exposure to antithrombotics was associated with reduced in-hospital mortality risk in adjusted analysis (aOR 0.54 [0.33, 0.86], P=0.01; aHR 0.65 [0.52, 0.82], P=0.0003). Subgroup analysis of adjusted estimates showed that exposure to aspirin (aHR 0.62 [0.50, 0.77], P<0.00001) and heparin (aOR 0.35 [0.14, 0.90], P=0.03) individually were associated with reduced mortality risk. The finding was robust to type of regimen, with pre-admission exposure to antithrombotics (aHR 0.79 [0.67, 0.93], P=0.005) and aspirin (aHR 0.66 [0.52, 0.84], P=0.0009] both showing reduced mortality risk. Additionally, prophylactic dose antithrombotics were associated with reduced mortality (aHR 0.44 [0.32, 0.60], P<0.00001). Publication bias was negative by Egger’s regression test (P=0.95). The direction of effect remained significantly in favor of intervention after trim-and-fill analysis (P=0.0034). Discussion: We make an interim recommendation in favor of antithrombotics, with very low certainty of evidence. We make an interim recommendation in favor of either intervention or non-intervention for both antiporphyrics and ESAs, with low and very low certainty of evidence.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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