Effect of polymerised type I collagen on hyperinflammation of adult outpatients with symptomatic COVID‐19

Abstract

Dear Editor, Although dexamethasone is approved for the hyperinflammation treatment of hospitalised COVID-19 patients, nonhospitalised patients do not benefit from this therapy. 1 A potential drug for treating COVID-19 patients is polymerised type I collagen (PTIC). A downregulator of proinflammatory cytokines, adhesion molecules (ELAM-1, VCAM-1, and ICAM-1), cyclooxygenase (Cox)-1 enzyme and the collagenases expression through the modulation of transcription of factor NF-kB. [2][3][4][5][6] The intramuscular or subcutaneous administration of PTIC to patients with active RA (Phase II studies) improved the count of swollen joints and morning stiffness; 57% of patients achieved an ACR score of 50, and 30% had disease remission with this therapeutic combination. PTIC was safe and well-tolerated in long-term treatment, without adverse effects. [7][8][9] A double-blind, randomised, placebo-controlled clinical trial evaluated the PTIC intramuscular administration's safety and efficacy on hyperinflammation, oxygen saturation and symptom improvement in adult symptomatic COVID-19 outpatients (https://www.medrxiv.org/content/ 10.1101/2021.05.12.21257133v1).Eighty-nine participants with a confirmed COVID-19 diagnosis (mild to moderate disease) were included from August 31 to November 7, 2020, and followed for 12 weeks. Patients were randomly assigned to receive either 1.5 ml of PTIC intramuscularly every 12 h for 3 days and then every 24 h for 4 days (n = 45) or a matching placebo (n = 44) (sample size is describe in Methodology S1). Demographics, clinical characteristics, coexisting conditions and symptoms are described in Table 1. Ninety-eight per cent of patients in the PTIC group and 95.5% in the placebo group were analysed by the intention-to-treat principle (Figure S1). Of 89 patients at baseline, 64 (72%) were being treated with acetaminophen, 28 (31.5%) with acetylsalicylic acid, 5 (5.6%) with antivirals and 36 (40.4%) with antibiotics. The use of acetaminophen (71% vs. 73%), acetylsalicylic acid (27% vs. 39%), antivirals (7% vs. 5%) and antibiotics (40% vs. 41%) were similar in the PTIC andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

An Update on the Clinical Efficacy and Safety of Collagen Injectables for Aesthetic and Regenerative Medicine Applications

“…While bovine collagen is used for many purposes, porcine collagen is almost exclusively used for the treatment of diseases belonging to the musculoskeletal apparatus [ 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ] (NCT02539030, NCT02519881, NCT02539095), followed by the integumental apparatus [ 67 , 76 , 86 , 87 , 147 , 148 , 149 , 150 , 151 , 152 ] (NCT03844529, NCT00891774, NCT00929071) and gastrointestinal apparatus [ 116 , 117 , 153 , 154 , 155 , 156 , 157 , 158 , 159 ]. Only recently porcine collagen potential has been explored for the treatment of facial nerve palsy [ 160 ] and for the treatment of COVID-19 due hyperinflammation [ 161 , 162 ] (NCT04517162). However, despite their wide use and effectiveness, bovine and porcine collagens suffer from cultural or religious concerns (bovine collagen: Sikh, Buddhism; porcine collagen: Jewish, Islamic faiths), which restricted their applicative potential [ 18 , 19 ].…”

“…New experimentations using collagen-based formulations were performed for non-standard clinical applications such as facial nerve rehabilitation after palsy [ 160 , 211 ], organ protection during thermal ablation [ 129 ], COVID-19 related hyperinflammation [ 161 , 162 ] (NCT04517162), artery aneurysms closure [ 128 , 213 ], blood volume augmentation [ 127 , 214 ] and the treatment of chronic ischemic heart diseases [ 226 ].…”

Targeting inflammation with collagen

“…A recent randomised, placebo‐controlled clinical trial demonstrated an innovative approach of treating symptomatic outpatient COVID‐19 infection by intramuscular injection of polymerised type I collagen (PTIC). 2 It was shown that PTIC has immunomodulatory properties and reduces the excessive release of inflammatory mediators arising due to cytokine release syndrome, which determines the clinical course, especially in the second week of infection. One day after completing the treatment, the patients in the treatment group presented a significant increase in mean oxygen saturation readings with values of 92% or higher as well as a shorter duration of symptoms (Figure 1 ).…”

“…One day after completing the treatment, the patients in the treatment group presented a significant increase in mean oxygen saturation readings with values of 92% or higher as well as a shorter duration of symptoms (Figure 1). 2 The present study delivers a novel approach of targeting systemic inflammation by administration of an F I G U R E 1 Polymerised type I collagen (PTIC) exhibits immunomodulatory effects in COVID-19. The PTIC-treated group showed significant improvement in disease severity.…”

“…A recent randomised, placebo‐controlled clinical trial demonstrated an innovative approach of treating symptomatic outpatient COVID‐19 infection by intramuscular injection of polymerised type I collagen (PTIC) 2 . It was shown that PTIC has immunomodulatory properties and reduces the excessive release of inflammatory mediators arising due to cytokine release syndrome, which determines the clinical course, especially in the second week of infection.…”