key: cord-0830345-lkaapewk
authors: Shakouri, Seyed Kazem; Roshangar, Leila; Mahmoodpoor, Ata
title: Intratracheal administration of autologus conditioned serum for COVID-19 associated respiratory distress syndrome
date: 2020-08-20
journal: J Crit Care
DOI: 10.1016/j.jcrc.2020.08.016
sha: d0ab71799281ee5eea165be87e9a08596c215c89
doc_id: 830345
cord_uid: lkaapewk

nan

From late 2019, China reported COVID-19 as an epidemic and in early 2020 WHO claimed it as a pandemic. Hospitalized patients may develop COVID-19 associated ARDS and cytokine storm leading to multi organ failure with a high mortality rate [1] .

Although there has been progress in understanding the mechanistic basis for the initiation and propagation of COVID-19, there is unfortunately not any specific and effective treatment or vaccine for COVID-19 [2, 3] . COVID-19 is associated with pulmonary inflammation and an increase in plasma concentrations of inflammatory cytokines (cytokine storm) due to dysregulated host immune respone [4] . There are many studies showing that COVID -19 is associated with immune response and hyperinflammation; so, therapeutic approaches targeting this pathway can help clinicians in the battle against this disease. Autologus conditioned serum (ACS) has been shown to be safe and effective on various disease especially osteoarthritis in previous clinical studies, all showing an excellent risk/benefit ratio [5] . ACS is enriched with anti-inflammatory cytokines like IL-1Ra, IL-10 and IL-13 and has low levels of inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and IL-1β [6] . Therapy is based on the injection of signaling protein-rich serum whose efficacy is due to the synergistic effect of many of the body's own signaling proteins (cytokines and growth factors) that are present in clinically relevant concentrations in ACS. Moreover, synergistic effects of IL-1Ra and other cytokines in addition to several regenerative growth factors are responsible for the strong and long lasting efficacy of ACS therapy in previous clinical studies. It has been shown that ACS can reduce the level of inflammatory cytokines in osteoarthritis patients after intra-articular injection.

As the most important organ dysfunction in COVID-19 is related to respiratory system, we tried to administer ACS intratracheally to get better distribution in different region of lungs. We used patients own plasma as it did not need matching and was a type of an autologous transfusion with lower risk of complications. Based on the inflammatory nature of COVID-19 and strong anti-inflammatory profile of ACS, we hypothesized that intratracheal administration of ACS to critically ill COVID-19 patients would result in improvement of the inflammatory and respiratory parameters of. The primary outcome was improvement in oxygenation and the secondary outcomes were duration of mechanical ventilation, ICU length of stay and respiratory indices such as compliance and resistance.

The study protocol was approved by the Ethics Committee of Tabriz University of Medical Sciences, which is in compliance with the Declaration of Helsinki. The off-label use of the method was verbally explained to the next of kin of each patient and written consent was obtained from all of them. The consent form included all the possible advantages and disadvantages of the method and its mechanism of action. The patients' information was J o u r n a l P r e -p r o o f Journal Pre-proof anonymous and analyzed in a coded format. No additional charges were paid by the patients at the end of the study, and the patients could abandon the study at any stage on personal desire. This is a preliminary data report of a clinical trial registered at http://www.irct.ir with registration number ID: IRCT20091012002582N21.

Five Patients with laboratory confirmed COVID-19, diagnosed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), were eligible to receive intratracheal ACS fulfilling the following criteria: COVID-19 associated respiratory distress syndrome being under mechanical ventilation with PaO 2 /FiO 2 less than 150. All patients received antiviral treatment (Hydroxy chloroquine 200 mg/12h and lopinavir/ritonavir 400 mg/12 h for 10 days), standard protocol and adjunct therapies for their disease. Severity of disease was assessed by clinical (hypoxemia, low Glascow Coma Scale, and high respiratory rate) and laboratory (high levels of D-dimer, LDH, CRP, CPK, BNP, and Ferritin) findings, and sequential organ failure assessment (SOFA) score. Thirty ml of blood was aseptically taken from each patient by EOT®II syringe. It was then incubated for 6-9 hours at 37° C and then the blood-filled syringes were centrifuged for 10 minute at 5000* rpm. The acquired serum (15 ml) was filtered (0.22 μm; Millipore, Carrigtwohill, Co. Cork, Ireland), separated into 3 tubes and frozen to −20°C till tracheal administration. The volume of injected autologous serum was based on previous researches [7] and the allowable volume which can be safely administered intratracheally without any complication. Thereafter, the plasma was intratracheally injected to each patient with co-administration of 5 ml distilled water which was followed by five manual breathing for a better distribution of plasma into different parts of the lungs. This procedure was repeated three times with the interval of three days. Before administration of ACS, tracheal suctioning was performed via closed suction system to ensure the removing of secretions from the lungs. We performed intratracheal administration under aseptic condition. To decrease the generation of aerosols, all patients received muscle relaxants before ACS injection and the ventilator circuit was blocked during the administration of ACS. Thereafter, we reconnected circuit as soon as possible and performed controlled ventilation for a better distribution of ACS to the distal parts. Meanwhile, the safety of our healthcare workers was also provided by LDH: lactate dehydrogenase BNP: brain natriuretic peptide CRP: C-reactive protein PCT: procalcitonin *Intergroup +Between groups J o u r n a l P r e -p r o o f

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

Drug treatment options for the 2019-new coronavirus (2019-nCoV)

COVID-19: consider cytokine storm syndromes and immunosuppression

Use of autologous conditioned serum (Orthokine®) for the treatment of the degenerative osteoarthritis of the temporomandibular joint. Review of the literature. Med Oral Patol Oral Cir Bucal

Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection

Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis

The authors declare no conflict of interest.