engleski

SARS-CoV-2 neutralization assay as a key premise for implementation of COVID-19 serotherapy in Croa-tia

Passive immunotherapy is a century-old practice of administering antibodies from an exposed convalescents or vaccinated persons to patients susceptible to the disease in question. Specific immunoglobulins, some even from animal sources, have an important role in the treatment of various clinical conditions, including viral diseases (hepatitis A and B, rabies, varicella, infections with respiratory syncytial virus, cytomegalovirus, measles). In situations where vaccines and specific drugs are not available, such as during emerging infections and pandemics (influenza, SARS-CoV-1, MERS, Ebola), convalescent plasma is being collected from donors who have recovered from the disease, and used to treat different pathogens. Experience from prior outbreaks with other coronaviruses (SARS-CoV-1) shows that such convalescent sera contain neutralising antibodies against relevant virus, and that their use was beneficial in the treated patients. Therapy with antibody-laden plasma of those who have survived an infection has nowadays been used and investigated worldwide. Although convalescent plasma therapy has been considered generally beneficial, scientific medical community lacks definitive proof of its effectiveness coming from carefully designed randomized clinical trials. Croatian approach to establish premises for COVID- 19 convalescent plasma (CCP) usage in a scientifically sound way, enabling also comparison of Croatian to international practice, will be presented. The approach included several steps: (i) development of a reproducible SARS-CoV-2 neutralisation potency assay in a single biosafety level three facility in Croatia ; (ii) establishment and continuous usage of an anti- SARS-CoV-2 in-house reference whose stability was monitored throughout the period of the assay lifetime ; (iii) search for the best fitting correlation function between results of in vitro commercial assays used by Croatian transfusion centres and the results of neutralisation assay, enabling that the neutralization potency of plasma doses used in the whole country could be expressed in the same way and in the same units ; (iv) and finally, and most importantly, we were able to express all neutralization potencies of plasma used in Croatia in relation to the first WHO international standard, by calibrating the assay’s internal reference to this international standard once it was established and available to the scientific community. Collection of COVID-19 convalescent plasma (CCP) at Croatian Institute of Transfusion Medicine (CITM) started in July 2020, the development of SARS-CoV-2 neutralization assay started in September 2020 and first unit for clinical use was issued in December 2020. Clinicians in Croatia started using CCP in second wave of pandemics, mostly for patients with hematological malignancies.

passive antibody therapy, convalescent plasma, COVID-19, SARS-CoV-2, wild-type virus neutralization assay

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