Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19
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Abstract
Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease.
Research question
What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection?
Study design and methods
We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching.
Results
Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28–0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients.
Interpretation
Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.
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SciScore for 10.1101/2021.06.16.21258972: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Yale University Institutional Review Board (HIC#: 2000027871) with a waiver of informed consent.
Consent: This study was approved by the Yale University Institutional Review Board (HIC#: 2000027871) with a waiver of informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Lim…
SciScore for 10.1101/2021.06.16.21258972: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Yale University Institutional Review Board (HIC#: 2000027871) with a waiver of informed consent.
Consent: This study was approved by the Yale University Institutional Review Board (HIC#: 2000027871) with a waiver of informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: The interpretation of our findings is limited by the observational nature of the study. However, propensity score matching to parse electronic medical record data is a valid and commonplace method in medical research.[20, 30] Matching characteristics were comparable between exposed and unexposed patients. We acknowledge that it is possible that despite the adequate matching, patients in the late cohort were intrinsically different from matched unexposed patients, and indication bias might have played a stronger role, or the late administration of CCP might not be an adequate rescue intervention. While results from multi-center, randomized, controlled trials will be available in the future, our study is the first adequately powered to evaluate CCP for use in moderate-to-severe disease. Although other studies may use different cut-offs for timing of CCP administration, our study used hospitalization date as a reliable time point that could be easily implemented to guide hospital treatment algorithms. It would be more challenging to establish timing of treatment based on the date of symptom onset, because initial COVID-related symptoms are often more difficult to precisely identify, and even more so in the early stages of the pandemic. Symptom onset information was also not feasible to obtain for our entire 2,551 patient cohort used for propensity matching. Another limitation of the present study is that each pool of plasma was unique without individual titer levels...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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