COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes

Focosi, Daniele; Franchini, Massimo; Pirofski, Liise-anne; Burnouf, Thierry; Paneth, Nigel; Joyner, Michael J.; Casadevall, Arturo

doi:10.1128/cmr.00200-21

Cited by 81 publications

(81 citation statements)

References 161 publications

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“…Multivariate analysis in our study showed that younger patients (<68 years) with less severe COVID-19 (i.e., admitted in low-intensity departments), where those who benefited the most from hyperimmune plasma-based therapy, particularly when it was administered early (<7 days from symptom onset) and at very high titer (>320). The latter finding is quite interesting as it confirms the most recent evidence from the literature showing a significant benefit of CCP among COVID-19 patients who received a larger amount of nAb [ 8 , 25 ].…”

Section: Discussionsupporting

confidence: 81%

“…Besides the CCP variability, differences in study design, patients’ characteristics and disease severity could have played a role. Nevertheless, we would like to highlight that most of the published RCT showed signals of CCP efficacy, including reductions in mortality, when subgroup analyses were restricted to the early use of high-titer CCP [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, these trials were heterogeneous with respect to the characteristics of the CCP used (e.g., in terms of antibody content and stratification of recipients according to their serological status or disease severity). Despite these limitations, there are currently positive signals from the literature on a beneficial effect of CCP when administered early (within 72 h from symptom onset) and with a high-titer (>1:160) of anti-SARS-CoV-2 neutralizing antibodies (nAb) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

Franchini

Glingani

Donno

et al. 2022

Life

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In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80–320). Their median age was 68 years (IQR, 56–78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

Franchini

Glingani

Donno

et al. 2022

Life

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“…Further data collected from RCTs have, however, globally reported the lack of efficacy of CCP in seropositive patients hospitalized for severe COVID-19 [ 3 ], hence its use was discouraged by the World Health Organization (WHO) and many scientific societies [ 4 , 5 , 6 ] and has rapidly declined since the third pandemic wave. Contrary to this trend, based on the safety of CCP [ 7 , 8 ] and on the positive signals of efficacy in subgroup analyses from RCTs and non-RCTs, [ 9 ] the US Food and Drug Administration (FDA) approved the Emergency Use Authorization (EUA) for high-titer COVID-19 convalescent plasma to patients with immunosuppressive disease or receiving immunosuppressive treatment [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients

Franchini

Focosi²,

Percivalle

et al. 2022

Viruses

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COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients’ median age was 66 years (IQR 50–74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.

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“…In this scenario, there is an urgent need for novel therapeutic agents. COVID-19 convalescent plasma (CCP) has been initially investigated as a treatment for COVID-19 inpatients [ 4 ], but findings from randomized controlled trials (RCT) have consistently shown definite efficacy only in outpatients treated within 5 days from onset of symptoms [ 5 , 6 , 7 ]. This is in line with indications for the usage of any other antiviral, including small-chemical and anti-Spike mAbs.…”

mentioning

confidence: 99%

Clinical and Virological Response to Convalescent Plasma in a Chronic Lymphocytic Leukemia Patient with COVID-19 Pneumonia

Belcari

Conti

Mazzoni³

et al. 2022

Life

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The burden of COVID-19 remains unchanged for immunocompromised patients who do not respond to vaccines. Unfortunately, Omicron sublineages are resistant to monoclonal antibodies authorized in Europe so far, and small chemical antivirals have contraindications and toxicities that have not been studied in these patients. We report here the successful treatment of COVID-19 pneumonia lasting for 4 months after the transfusion of COVID-19 convalescent plasma (CCP) in a patient with severe immunosuppression due to both chronic lymphocytic leukemia and venetoclax treatment. The patient achieved a complete clinical, radiological and virological response after six transfusions (600 mL each) of high-titer CCP collected from triple-vaccinated and convalescent donors. This dramatic case adds to the mounting evidence of CCP efficacy in immunocompromised patients, provided that high-titer and large volumes are infused.

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COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes

Cited by 81 publications

References 161 publications

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients

Clinical and Virological Response to Convalescent Plasma in a Chronic Lymphocytic Leukemia Patient with COVID-19 Pneumonia

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