Characterization of CCP: Can We Use Past Convalescent Plasma from COVID-19 Patients for Treatment of New Emerging Variants?

Background and Objectives: New SARS-CoV-2 variants may impact the effectiveness of previously stored convalescent plasma (CCP). We defined levels of anti-delta and anti-omicron SARS-CoV-2 neutralizing antibodies (Nt-Abs) and investigated possible differences of past CCP Nt-Abs responses related to donor location in North and South Italy. Methods: Serum from 153 donors recovered from SARS-COV-2 infection (98 from northern and 55 from southern Italy) were analyzed for Nt-Abs characterization using our in house microneutralization assay. Results were compared to anti-Spike IgG measured by chemiluminescent assay (CLIA) to define a possible agreement with a more affordable test. Results: delta Nt-Abs titer in comparison to the reference strain (PV10734 D614G) showed a reduction of 82% in northern and 77% in southern Italy groups. Omicron Nt-Abs titer showed a reduction of 97%. CCP corresponding to Nt-Abs titer > 1:80 showed a median of 1365 BAU/mL for delta strain and 653 BAU/mL for reference strain. We found no statistical differences between Nt-Abs responses in North and South CCP donors. Conclusions: Not all past CCP could be used to treat patients with SARS-CoV-2 delta and omicron infections due to the lack of specific Nt-Abs. For the moment, the neutralization test remains the gold standard to select potential CCP donors. Interestingly, our study did not find NT-Abs differences between plasma collected from donors living in different areas of Italy.

A retrospective study assessing the characteristics of COVID-19 convalescent plasma donors and donations.

BACKGROUND: Although many trials are currently investigating the safety and efficacy of convalescent plasma (CP) in critically ill COVID-19 patients, there is a paucity of ongoing and published studies evaluating the CP donors' side. This retrospective study reports the first Italian experience on CP donors' selection and donations. METHODS: Patients aged 18-68 years who had recovered from COVID-19 at least 2 weeks previously were recruited between March 18 and June 30, 2020 in a study protocol at the Italian hospitals of Pavia and Mantova. RESULTS: During the study period, 494 of 512 donors recruited were judged eligible and underwent 504 plasmapheresis procedures. Eighty-five percent (437/512) of the CP donors were males. The average time between symptom recovery and CP donation was 36.6 (±20.0) days. Four hundred and eighty-eight plasmapheresis procedures (96.8%) were concluded and each unit was divided into two subunits (total 976) with an average volume of 316.2 (±22.7) mL. Ninety-three percent (460/494) of CP donors at the time of plasma donation had a neutralizing IgG titer ≥1:80. Plasmapheresis-related adverse reactions occurred in 2.6% (13/504) of cases; all the reactions were mild and none required therapeutic intervention. Donors' age and COVID-19 severity were positively associated with greater antibody responses. CONCLUSION: This study demonstrates the feasibility and safety of a pilot CP program conducted in Italy. The identification of factors (ie, age and severity of COVID-19) positively associated with higher neutralizing antibody titers at the time of donation may help to optimize the selection of CP donors.

Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial.

Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19. We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, of them, 30 were on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Bilateral infiltrates on chest X-ray was present in 36 patients (84%). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days as compared to an expected 15% from the National Statistics and 30% from a small concurrent cohort of 23 patients. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). In conclusion, Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.

Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol.

Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.