Janaka Sanath Kumar, Hartman William, Mou Huihui, Farzan Michael, Stramer Susan L, Goodhue Erin, Weiss John, Evans David, Connor Joseph P
medRxiv. 2021 Mar 1:2021.02.25.21252463. doi: 10.1101/2021.02.25.21252463.
The novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP.
To identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients.
Viral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients.
Since viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.
导致COVID-19的新型冠状病毒SARS-CoV2在过去一年中已导致超过231万人死亡,然而目前尚无治愈方法。虽然使用COVID-19康复期血浆(CCP)进行被动免疫提供了一种安全可行的选择,但选择最佳治疗单位以及输血缺乏明确的治疗益处仍然是CCP使用的障碍。
为了确定预期能使接受者受益的血浆,我们使用临床可用的血清学检测方法测量了抗SARS-CoV2抗体水平,并将其与供体CCP的中和活性相关联。通过在血浆样品稀释液存在下测定SARS-CoV-2刺突蛋白假型逆转录病毒颗粒的感染性来测量血浆样品的中和滴度。我们还使用该检测方法来确定CCP接受者中被动输注中和活性的证据。
来自87名血浆供体的109个样品中的病毒中和和抗刺突蛋白抗体差异很大,但彼此之间存在适度的相关性。发现死于COVID-19的接受者输注的单位抗刺突抗体水平和中和活性较低。在62%的未接触过抗体的血浆接受者中记录到了中和活性的被动转移。
由于病毒中和是CCP输血的目标,我们的观察结果不仅支持使用抗SARS-CoV2刺突血清学检测来识别有益的CCP单位,也支持高滴度抗刺突抗体康复期血浆的治疗价值。