Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma: a prospective study
Authors: Donato Michele L , Park Steven , Baker Melissa , Korngold Robert , Morawski Alison , Geng Xue , Tan Ming , Ip Andrew , Goldberg Stuart , Rowley Scott , Chow Kar , Brown Emily , Zenreich Joshua , McKiernan Phyllis , Buttner Kathryn , Ullrich Anna , Long Laura , Feinman Rena , Rincourt Andrea , Kemp Marlo , Vendivil Mariefel , Suh Hyung , Balani Bindu , Cicogna Cristina , Sebti Rani , Al-Khan Abdulla , Sperber Steven , Desai Samit , Fanning Stacey , Arad Danit , Go Ronaldo , Tam Elizabeth , Rose Keith , Sadikot Sean , Siegel David , Gutierrez Martin , Feldman Tatyana , Goy Andre , Pecora Andrew , Biran Noa , Leslie Lori , Gillio Alfred , Timmapuri Sarah , Boonstra Michele , Singer Sam , Kaur Sukhdeep , Richards Ernest , Perlin David S 
Published: July 2020

OBJECTIVES

To determine the rate of intubation, overall survival, viral clearance, and the development of endogenous antibodies in patients with COVID-19 pneumonia treated with convalescent plasma containing high levels of neutralizing anti-SARS-CoV-2 antibodies. We also aimed to describe the laboratory parameters of the plasma products.

DESIGN

This was a phase IIa, single institution, prospective study in adults hospitalized with SARS-CoV-2 pneumonia.

SETTING

Hackensack University Medical Center, a 770-bed research and teaching hospital located in Bergen County NJ, 11 km from New York City. The study was conducted between April 15 and June 18, 2020.

PARTICIPANTS

47 hospitalized adult patients were treated: 32 in the non-mechanically ventilated group and 15 in the mechanically ventilated group. All patients had confirmed SARS-CoV-2 pneumonia by radiographic and laboratory evaluation.

INTERVENTION

Fresh or frozen convalescent plasma from donors with high titers of viral neutralizing antibodies was administered.

MAIN OUTCOME MEASURES

Incidence of intubation, overall survival, and discharge rate of patients divided in cohorts based on severity of disease. Description of infused plasma characteristics. Evaluation of recipients’ pre-treatment viral immunity, immunity transfer from convalescent plasma administration, and late immunity 30 and 60 days after treatment. Rates of viral clearance by nasopharyngeal PCR at 10 and 30 days. Outcomes of patients with no pre-treatment immunity. Survival comparison with institutional data for each cohort.

RESULTS

Analysis for the non-mechanically ventilated patients showed an intubation rate of 15.6% (95% CI: 5.3%-32.8%) and a day-30 survival rate of 87.5% (28/32; 95% CI:70.2%-96.4%). The overall survival for a comparative group based on institutional data was 66% (675/1023; p=0.012). The rates of negative nasopharyngeal swab by PR-PCR on day+10 and +30 post treatment were 42.9% (95% CI: 24%-63%) and 78% (95% CI: 56%-93%) respectively. Patients mechanically ventilated had a day-30 mortality of 46.7% (95% CI:21.3%-73.4%); the mortality for a comparative group based on institutional data was 68.5% (217/317; p=0.093). The rates of negative nasopharyngeal swab by PR-PCR at day+10 and +30 was 85.7% (95% CI: 42-100%; n=7) and 100% (95% CI: 63-100%; n=8). Seven patients (15%) had no pre-infusion immunity, and all were found to have anti-SARS-CoV-2 neutralizing titers three days post infusion. All evaluable patients were found to have neutralizing antibodies on day+30 (n=30) and on day+60 (n=12) post treatment. There was no difference in outcomes within the ranges of high antiviral neutralizing titers used, mostly greater than 1:1000. There was also no difference between fresh or frozen plasma. The only adverse event was a mild rash in one patient.

CONCLUSION

In this study of adult patients hospitalized with SARS-CoV-2 pneumonia, convalescent plasma was safe and conferred effective transfer of immunity while preserving endogenous immune response. Intubation rates, survival rates compared with institutional data, and viral clearance rates, support the continued evaluation of this antiviral modality.

STUDY REGISTRATION

ClinicalTrials.gov NTC04343755