Convalescent Plasma for Critically-ill Covid-19 Patients

preprint OA: closed CC-BY-4.0
📄 Open PDF Full text JSON View at publisher
Full text 37,870 characters · extracted from preprint-html · click to expand
Convalescent Plasma for Critically-ill Covid-19 Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Convalescent Plasma for Critically-ill Covid-19 Patients Adel A. Aljatham, Waleed T. Hashim, Mohamad A. Almashiakhi, Abdulrahman M. Alharthy, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3911163/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and aim: Convalescent plasma (CP) was early and successfully used in management of covid-19 infection. This report aimed to document our experience with use of CP in two critically-ill covid-19 patients. Main findings: Patients presented with fever, dry cough and difficulty of breathing with reduced oxygen saturation, massive radiological lung involvement and deteriorated Sequential Organ Failure Assessment (SOFA) Score. Use of two sessions of CP resulted in marked improvement of radiological and/or pulmonary findings. Both patients died of septic shock or thromboembolic events. Conclusions Use of CP may be associated with radiological and clinical improvement in critically-ill patients. However, it’s not related to better survival if used in late stages of the disease. Internal Medicine Covid-19 Passive immunization Convalescent plasma Figures Figure 1 Introduction The overwhelming challenge caused by COVID-19 pandemic triggered an unprecedented global effort to identify and develop effective medications and vaccines against the disease with different pathological targets, mechanisms, adverse effects and clinical outcomes [ 1 ]. Generally, these therapeutics include antiviral and immunomodulatory agents [ 2 ]. Among the immunomodulatory agents, passive antibody therapies including neutralizing monoclonal antibodies (mAbs), hyperimmunoglobulin and convalescent plasma (CP) have been early and successfully used [ 3 ]. In comparison with monocloncal antibodies, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against new variants [ 4 ]. In this report, we document our experience with use of CP in two critically-ill covid-19 patients in the early months of the pandemic. The legal guardians of the included patients provided consent to anonymously publish this report. Case scenarios The first patient a 65-year-old male with history of hypertension. He presented to ER department in June, 2020 with 11-day history of fever, dry cough and difficulty of breathing. His peripheral oxygen saturation was 92.0% while receiving 15 L/min. of oxygen via facemask. The patient was prompted to full laboratory assessment and radiological imaging. Laboratory findings are shown in figure.1 Sequential Organ Failure Assessment (SOFA) Score was calculated to be 5 and chest radiograph revealed 70.0% of lung involvement with infiltrates. The patient was admitted to the ICU where he remained spontaneously breathing for 4 days. On deterioration of partial pressure of oxygen / fraction of inspired oxygen (P/F) ratio to 80, he was switched to mechanical ventilation (MV) and maintained on full sedation and vasopressor support. During ICU stay, the patient received anti-viral medications, steroids, tocilizumab and multiple courses of antibiotics according to culture and sensitivity (ceftriaxone initially, followed by azithromycin, then linezolid and imipenem). In addition, he received two sessions of CP (10–15 ml/kg infusion); the first at day 2 after initiation of MV and the second at day 4. CP administration resulted in marked improvement of chest radiographs to 50.0% and 40.0% of lung tissue involvement after the first and second sessions respectively. Also, P/F ratio improved to 500 at day 7 and tested negative for COVID-19 at day 13 of CP initiation. Unfortunately, however, the patient finally died after 45 days of ICU admission due to perforated acalculous cholecystitis, septic shock (main isolated organisms: acintobacter baumani and staphylococcus capitis ) and multi-organ failure. The second patient is 68-year-old male with history of hypertension, diabetes, coronary heart disease, multiple disc herniations mainly L5-S1 and transient ischemic attacks. Upon presentation to ER in July, 2020, he had complained of fever, dry cough, and difficulty of breathing for 3 days. He had a peripheral oxygen saturation of 91% while receiving 10 L/min. of oxygen via facemask. Laboratory and radiological assessment identified a SOFA score of 4 and bilateral infiltration involving 40% of lungs fields. More laboratory details are illustrated in Fig. 1 . The patient was admitted to ICU where he received anti-viral therapy, steroids, tocilizumab and empirical antibiotics (started with azithromycin and followed by complete courses of cefepime, vancomycin, and meropenim) due to lack positive cultures from any source. Three days after admission, radiological lung involvement extended to involve 80.0% of lung tissue. On the same day CP administration was initiated and the patient received two sessions. Radiological involvement was reduced to 50.0% and 40.0% of lung tissue at days 14 and 30 after CP use and Covid-19 test turned negative after 15 days of ICU admission. In spite of this improvement, the patient ultimately died after 93 days of ICU admission probably due to thromboembolic events. Discussion The present case report illustrates the clinical scenarios of two critically-ill covid-19 patients who received CP during their ICU stay. While CP administration resulted in marked improvement of radiological findings and/or pulmonary functions, both patients finally died. The unfavorable outcome in our patients is probably attributed to the late use of CP. At this time, the patient usually has developed his own immune response which -if exaggerated- can result in cytokine storm and its consequences. Unfortunately, at the early months of the pandemic, no standardized protocols were available for CP administration. This suggestion is supported by the conclusions of a recent meta-analysis of 58 randomized controlled trials. It was found that efficacy of CP is better when used in early disease stages [ 5 ]. In fact, the value of CP in management of covid-19 patients is a controversial issue. One meta-analysis dedicated for studies involving outpatient covid-19 patients revealed that patients who received CP, experienced lower rate of hospitalization with no benefit on survival or clinical outcome [ 6 ]. In contrast, another meta-analysis including the same subset of patients found that CP use was able to reduce all-cause mortality particularly when used within 5 days of symptom onset [ 7 ]. In hospitalized patients, use of CP resulted in reduction of mortality rate especially when preparations with high antibody levels were used or when CP was used early after hospitalization [ 8 ]. However, one case series acknowledged the efficacy and safety of CP even in late-state and severe cases of covid-19 infection with significant improvement of clinical and laboratory findings and final discharge of 75.0% of patients [ 9 ]. In contrast, other studies concluded that CP use has no effect on mortality [ 10 , 11 ] principally in patients with moderate-to-severe illness [ 12 ]. This controversy may be explained by the variable clinical characteristics of the studied patients and the variable preparations and protocols of CP administration in different centers. This explanation is supported by the conclusions of Casadevall et al. [ 13 ] who identified three conditions for successful use of CP in covid-19 patients: 1) Use of specific antibody, 2) early use and 3) sufficient amount of antibodies. Conclusions Use of CP has beneficial influence on clinical and radiological findings in covid-19 patients. However, late administration has no impact on their survival. Declarations This study was approved by the ethical committee of King Saud Medical City References Aboul-Fotouh S, Mahmoud AN, Elnahas EM, Habib MZ, Abdelraouf SM. What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms. Virol J. 2023 Oct 24;20(1):241. doi: 10.1186/s12985-023-02210-z. PMID: 37875904; PMCID: PMC10594888. Andrews HS, Herman JD, Gandhi RT. Treatments for COVID-19. Annu Rev Med. 2023 Sep 18. doi: 10.1146/annurev-med-052422-020316. Epub ahead of print. PMID: 37722709. Yang X. Passive antibody therapy in emerging infectious diseases. Front Med. 2023 Dec 2. doi: 10.1007/s11684-023-1021-y. Epub ahead of print. PMID: 38040914. Schrezenmeier H, Hoffmann S, Hofmann H, Appl T, Jahrsdörfer B, Seifried E, Körper S. Immune Plasma for the Treatment of COVID-19: Lessons Learned so far. Hamostaseologie. 2023 Feb;43(1):67-74. doi: 10.1055/a-1987-3682. Epub 2023 Feb 20. PMID: 36807822. Stadler E, Chai KL, Schlub TE, Cromer D, Khan SR, Polizzotto MN, Kent SJ, Beecher C, White H, Turner T, Skoetz N, Estcourt L, McQuilten ZK, Wood EM, Khoury DS, Davenport MP. Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis. Lancet Microbe. 2023 Nov;4(11):e883-e892. doi: 10.1016/S2666-5247(23)00194-5. PMID: 37924835. Filippatos C, Ntanasis-Stathopoulos I, Sekeri K, Ntanasis-Stathopoulos A, Gavriatopoulou M, Psaltopoulou T, Dounias G, Sergentanis TN, Terpos E. Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials. Viruses. 2023 Mar 16;15(3):765. doi: 10.3390/v15030765. PMID: 36992474; PMCID: PMC10054551. Levine AC, Fukuta Y, Huaman MA, Ou J, Meisenberg BR, Patel B, Paxton JH, Hanley DF, Rijnders BJA, Gharbharan A, Rokx C, Zwaginga JJ, Alemany A, Mitjà O, Ouchi D, Millat-Martinez P, Durkalski-Mauldin V, Korley FK, Dumont LJ, Callaway CW, Libster R, Marc GP, Wappner D, Esteban I, Polack F, Sullivan DJ. Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials. Clin Infect Dis. 2023 Jun 16;76(12):2077-2086. doi: 10.1093/cid/ciad088. PMID: 36809473; PMCID: PMC10273382. Senefeld JW, Gorman EK, Johnson PW, Moir ME, Klassen SA, Carter RE, Paneth NS, Sullivan DJ, Morkeberg OH, Wright RS, Fairweather D, Bruno KA, Shoham S, Bloch EM, Focosi D, Henderson JP, Juskewitch JE, Pirofski LA, Grossman BJ, Tobian AAR, Franchini M, Ganesh R, Hurt RT, Kay NE, Parikh SA, Baker SE, Buchholtz ZA, Buras MR, Clayburn AJ, Dennis JJ, Diaz Soto JC, Herasevich V, Klompas AM, Kunze KL, Larson KF, Mills JR, Regimbal RJ, Ripoll JG, Sexton MA, Shepherd JRA, Stubbs JR, Theel ES, van Buskirk CM, van Helmond N, Vogt MNP, Whelan ER, Wiggins CC, Winters JL, Casadevall A, Joyner MJ. Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis. Mayo Clin Proc Innov Qual Outcomes. 2023 Oct 10;7(5):499-513. doi: 10.1016/j.mayocpiqo.2023.09.001. PMID: 37859995; PMCID: PMC10582279. Kumar NR, Karanam VC, Kumar S, Kumar SD. Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection. South Med J. 2023 May;116(5):427-433. doi: 10.14423/SMJ.0000000000001546. PMID: 37137479; PMCID: PMC10143395. Mihalek N, Radovanović D, Barak O, Čolović P, Huber M, Erdoes G. Convalescent plasma and all-cause mortality of COVID-19 patients: systematic review and meta-analysis. Sci Rep. 2023 Aug 9;13(1):12904. doi: 10.1038/s41598-023-40009-8. PMID: 37558729; PMCID: PMC10412555. Hakim SM, Chikhouni GMA, Ammar MA, Amer AM. Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis. J Anesth. 2023 Jun;37(3):451-464. doi: 10.1007/s00540-023-03171-x. Epub 2023 Feb 22. PMID: 36811668; PMCID: PMC9944423. Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6. PMID: 37162745; PMCID: PMC10171886. Casadevall A, Joyner MJ, Pirofski LA, Senefeld JW, Shoham S, Sullivan D, Paneth N, Focosi D. Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy. Expert Rev Respir Med. 2023 May;17(5):381-395. doi: 10.1080/17476348.2023.2208349. Epub 2023 May 2. PMID: 37129285. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3911163","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":270080510,"identity":"88b36d27-48ac-4711-8487-5fc6eb389925","order_by":0,"name":"Adel A. Aljatham","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYDACdoYEBsYGBgZ+BgY2IrUwA7UcBGqRbCBBCwNYi8EBYrXwNzM8/Pxxh1208Y3kZw8+VDDI84sdwK9F4jBDssTBM8m5226kmRvOOMNgOHN2AgFrDjMkSBxsYwZqSTCT5m1jSDC4TUCLPNCWHwfb6nM3z0j/RpwWg8MMaUBbDudukMgh0hZDoBaLs23Hc2eceVMmOeOMBGG/yB3vSb5R2Vad29+evk3iQ4WNPL80AS0MDDxQFQJgWoKQchBgPwCh+Q8Qo3oUjIJRMApGIgAAm1NH1JWX/ssAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0001-0200-7690","institution":"King Saud Medical City","correspondingAuthor":true,"prefix":"","firstName":"Adel","middleName":"A.","lastName":"Aljatham","suffix":""},{"id":270080511,"identity":"b1378646-4b5e-4bbe-a92e-3e665194efe1","order_by":1,"name":"Waleed T. Hashim","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Waleed","middleName":"T.","lastName":"Hashim","suffix":""},{"id":270080512,"identity":"e0e73fc6-4524-4ca7-8e3f-01cfa142f903","order_by":2,"name":"Mohamad A. Almashiakhi","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Mohamad","middleName":"A.","lastName":"Almashiakhi","suffix":""},{"id":270080513,"identity":"6a30ad9a-ce99-4c7b-a7c3-66e49e89efee","order_by":3,"name":"Abdulrahman M. Alharthy","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Abdulrahman","middleName":"M.","lastName":"Alharthy","suffix":""},{"id":270080514,"identity":"d98e1780-0c2a-44cb-913d-684e0adfc9cf","order_by":4,"name":"Faisal A. Alaklobi","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Faisal","middleName":"A.","lastName":"Alaklobi","suffix":""},{"id":270080515,"identity":"023b2e53-b377-4b88-ad8b-97269a25c82c","order_by":5,"name":"Mohammed Adam","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Adam","suffix":""},{"id":270080516,"identity":"5ba1fe4a-4c2f-4281-acc6-ea863d1474e3","order_by":6,"name":"Assem A. Elghazaly","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Assem","middleName":"A.","lastName":"Elghazaly","suffix":""},{"id":270080517,"identity":"af6091fe-7bc1-4b56-9e98-3e418b932ef0","order_by":7,"name":"Ahmed F. Mady","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"F.","lastName":"Mady","suffix":""},{"id":270080518,"identity":"38da8f3d-760b-4370-9752-1bd76e870850","order_by":8,"name":"Daood S. Asad","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Daood","middleName":"S.","lastName":"Asad","suffix":""},{"id":270080519,"identity":"69db4425-d97d-4c18-b8ff-bc3c0d02ba69","order_by":9,"name":"Hala Aamr","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Hala","middleName":"","lastName":"Aamr","suffix":""},{"id":270080520,"identity":"57870b2d-28d4-40d0-904f-ba0e995e97e4","order_by":10,"name":"Alaa H. Alali","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Alaa","middleName":"H.","lastName":"Alali","suffix":""},{"id":270080521,"identity":"685a7be5-89bb-4853-848d-28d57924e4e2","order_by":11,"name":"Juhaina Abdlraheem","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Juhaina","middleName":"","lastName":"Abdlraheem","suffix":""},{"id":270080522,"identity":"a20fb755-e56f-42e9-8c73-ce76d1e95c43","order_by":12,"name":"Muhned S. Alhumaid","email":"","orcid":"","institution":"King Saud Medical City","correspondingAuthor":false,"prefix":"","firstName":"Muhned","middleName":"S.","lastName":"Alhumaid","suffix":""},{"id":270080523,"identity":"d5cfd98e-2139-4e15-8b0a-864e31876984","order_by":13,"name":"Mohammed A. Aljatham","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"A.","lastName":"Aljatham","suffix":""},{"id":270080524,"identity":"ebf4e8a5-95a6-443d-9119-1feb5cc0d0db","order_by":14,"name":"Khalid I. Zawbaee","email":"","orcid":"","institution":"Riyadh Regional Blood Bank","correspondingAuthor":false,"prefix":"","firstName":"Khalid","middleName":"I.","lastName":"Zawbaee","suffix":""}],"badges":[],"createdAt":"2024-01-30 16:23:13","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3911163/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3911163/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50564796,"identity":"a77dccef-1107-4091-9c65-03154bfbc156","added_by":"auto","created_at":"2024-02-02 15:06:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":261734,"visible":true,"origin":"","legend":"\u003cp\u003eLaboratory findings in the studied cases\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3911163/v1/50998d9a57fe99b303e1661c.png"},{"id":50564797,"identity":"5531235b-90e3-4332-92c0-9073b5d2a621","added_by":"auto","created_at":"2024-02-02 15:06:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":403894,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3911163/v1/2c2870ac-4c57-401c-b104-01cc66239e66.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eConvalescent Plasma for Critically-ill Covid-19 Patients\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe overwhelming challenge caused by COVID-19 pandemic triggered an unprecedented global effort to identify and develop effective medications and vaccines against the disease with different pathological targets, mechanisms, adverse effects and clinical outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Generally, these therapeutics include antiviral and immunomodulatory agents [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Among the immunomodulatory agents, passive antibody therapies including neutralizing monoclonal antibodies (mAbs), hyperimmunoglobulin and convalescent plasma (CP) have been early and successfully used [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In comparison with monocloncal antibodies, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against new variants [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this report, we document our experience with use of CP in two critically-ill covid-19 patients in the early months of the pandemic. The legal guardians of the included patients provided consent to anonymously publish this report.\u003c/p\u003e"},{"header":"Case scenarios","content":"\u003cp\u003eThe first patient a 65-year-old male with history of hypertension. He presented to ER department in June, 2020 with 11-day history of fever, dry cough and difficulty of breathing. His peripheral oxygen saturation was 92.0% while receiving 15 L/min. of oxygen via facemask. The patient was prompted to full laboratory assessment and radiological imaging. Laboratory findings are shown in figure.1 Sequential Organ Failure Assessment (SOFA) Score was calculated to be 5 and chest radiograph revealed 70.0% of lung involvement with infiltrates. The patient was admitted to the ICU where he remained spontaneously breathing for 4 days. On deterioration of partial pressure of oxygen / fraction of inspired oxygen (P/F) ratio to 80, he was switched to mechanical ventilation (MV) and maintained on full sedation and vasopressor support. During ICU stay, the patient received anti-viral medications, steroids, tocilizumab and multiple courses of antibiotics according to culture and sensitivity (ceftriaxone initially, followed by azithromycin, then linezolid and imipenem). In addition, he received two sessions of CP (10\u0026ndash;15 ml/kg infusion); the first at day 2 after initiation of MV and the second at day 4. CP administration resulted in marked improvement of chest radiographs to 50.0% and 40.0% of lung tissue involvement after the first and second sessions respectively. Also, P/F ratio improved to 500 at day 7 and tested negative for COVID-19 at day 13 of CP initiation. Unfortunately, however, the patient finally died after 45 days of ICU admission due to perforated acalculous cholecystitis, septic shock (main isolated organisms: \u003cem\u003eacintobacter baumani\u003c/em\u003e and \u003cem\u003estaphylococcus capitis\u003c/em\u003e) and multi-organ failure.\u003c/p\u003e \u003cp\u003eThe second patient is 68-year-old male with history of hypertension, diabetes, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ecoronary\u003c/span\u003e heart disease, multiple disc herniations mainly L5-S1 and transient ischemic attacks. Upon presentation to ER in July, 2020, he had complained of fever, dry cough, and difficulty of breathing for 3 days. He had a peripheral oxygen saturation of 91% while receiving 10 L/min. of oxygen via facemask. Laboratory and radiological assessment identified a SOFA score of 4 and bilateral infiltration involving 40% of lungs fields. More laboratory details are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe patient was admitted to ICU where he received anti-viral therapy, steroids, tocilizumab and empirical antibiotics (started with azithromycin and followed by complete courses of cefepime, vancomycin, and meropenim) due to lack positive cultures from any source. Three days after admission, radiological lung involvement extended to involve 80.0% of lung tissue. On the same day CP administration was initiated and the patient received two sessions. Radiological involvement was reduced to 50.0% and 40.0% of lung tissue at days 14 and 30 after CP use and Covid-19 test turned negative after 15 days of ICU admission. In spite of this improvement, the patient ultimately died after 93 days of ICU admission probably due to thromboembolic events.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present case report illustrates the clinical scenarios of two critically-ill covid-19 patients who received CP during their ICU stay. While CP administration resulted in marked improvement of radiological findings and/or pulmonary functions, both patients finally died. The unfavorable outcome in our patients is probably attributed to the late use of CP. At this time, the patient usually has developed his own immune response which -if exaggerated- can result in cytokine storm and its consequences. Unfortunately, at the early months of the pandemic, no standardized protocols were available for CP administration.\u003c/p\u003e \u003cp\u003eThis suggestion is supported by the conclusions of a recent meta-analysis of 58 randomized controlled trials. It was found that efficacy of CP is better when used in early disease stages [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn fact, the value of CP in management of covid-19 patients is a controversial issue. One meta-analysis dedicated for studies involving outpatient covid-19 patients revealed that patients who received CP, experienced lower rate of hospitalization with no benefit on survival or clinical outcome [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In contrast, another meta-analysis including the same subset of patients found that CP use was able to reduce all-cause mortality particularly when used within 5 days of symptom onset [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn hospitalized patients, use of CP resulted in reduction of mortality rate especially when preparations with high antibody levels were used or when CP was used early after hospitalization [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, one case series acknowledged the efficacy and safety of CP even in late-state and severe cases of covid-19 infection with significant improvement of clinical and laboratory findings and final discharge of 75.0% of patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, other studies concluded that CP use has no effect on mortality [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] principally in patients with moderate-to-severe illness [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This controversy may be explained by the variable clinical characteristics of the studied patients and the variable preparations and protocols of CP administration in different centers.\u003c/p\u003e \u003cp\u003eThis explanation is supported by the conclusions of Casadevall et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] who identified three conditions for successful use of CP in covid-19 patients: 1) Use of specific antibody, 2) early use and 3) sufficient amount of antibodies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eUse of CP has beneficial influence on clinical and radiological findings in covid-19 patients. However, late administration has no impact on their survival.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis study was approved by the ethical committee of King Saud Medical City\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAboul-Fotouh S, Mahmoud AN, Elnahas EM, Habib MZ, Abdelraouf SM. What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms. Virol J. 2023 Oct 24;20(1):241. doi: 10.1186/s12985-023-02210-z. PMID: 37875904; PMCID: PMC10594888.\u003c/li\u003e\n\u003cli\u003eAndrews HS, Herman JD, Gandhi RT. Treatments for COVID-19. Annu Rev Med. 2023 Sep 18. doi: 10.1146/annurev-med-052422-020316. Epub ahead of print. PMID: 37722709.\u003c/li\u003e\n\u003cli\u003eYang X. Passive antibody therapy in emerging infectious diseases. Front Med. 2023 Dec 2. doi: 10.1007/s11684-023-1021-y. Epub ahead of print. PMID: 38040914.\u003c/li\u003e\n\u003cli\u003eSchrezenmeier H, Hoffmann S, Hofmann H, Appl T, Jahrsd\u0026ouml;rfer B, Seifried E, K\u0026ouml;rper S. Immune Plasma for the Treatment of COVID-19: Lessons Learned so far. Hamostaseologie. 2023 Feb;43(1):67-74. doi: 10.1055/a-1987-3682. Epub 2023 Feb 20. PMID: 36807822.\u003c/li\u003e\n\u003cli\u003eStadler E, Chai KL, Schlub TE, Cromer D, Khan SR, Polizzotto MN, Kent SJ, Beecher C, White H, Turner T, Skoetz N, Estcourt L, McQuilten ZK, Wood EM, Khoury DS, Davenport MP. Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis. Lancet Microbe. 2023 Nov;4(11):e883-e892. doi: 10.1016/S2666-5247(23)00194-5. PMID: 37924835.\u003c/li\u003e\n\u003cli\u003eFilippatos C, Ntanasis-Stathopoulos I, Sekeri K, Ntanasis-Stathopoulos A, Gavriatopoulou M, Psaltopoulou T, Dounias G, Sergentanis TN, Terpos E. Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials. Viruses. 2023 Mar 16;15(3):765. doi: 10.3390/v15030765. PMID: 36992474; PMCID: PMC10054551.\u003c/li\u003e\n\u003cli\u003eLevine AC, Fukuta Y, Huaman MA, Ou J, Meisenberg BR, Patel B, Paxton JH, Hanley DF, Rijnders BJA, Gharbharan A, Rokx C, Zwaginga JJ, Alemany A, Mitj\u0026agrave; O, Ouchi D, Millat-Martinez P, Durkalski-Mauldin V, Korley FK, Dumont LJ, Callaway CW, Libster R, Marc GP, Wappner D, Esteban I, Polack F, Sullivan DJ. Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials. Clin Infect Dis. 2023 Jun 16;76(12):2077-2086. doi: 10.1093/cid/ciad088. PMID: 36809473; PMCID: PMC10273382.\u003c/li\u003e\n\u003cli\u003eSenefeld JW, Gorman EK, Johnson PW, Moir ME, Klassen SA, Carter RE, Paneth NS, Sullivan DJ, Morkeberg OH, Wright RS, Fairweather D, Bruno KA, Shoham S, Bloch EM, Focosi D, Henderson JP, Juskewitch JE, Pirofski LA, Grossman BJ, Tobian AAR, Franchini M, Ganesh R, Hurt RT, Kay NE, Parikh SA, Baker SE, Buchholtz ZA, Buras MR, Clayburn AJ, Dennis JJ, Diaz Soto JC, Herasevich V, Klompas AM, Kunze KL, Larson KF, Mills JR, Regimbal RJ, Ripoll JG, Sexton MA, Shepherd JRA, Stubbs JR, Theel ES, van Buskirk CM, van Helmond N, Vogt MNP, Whelan ER, Wiggins CC, Winters JL, Casadevall A, Joyner MJ. Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis. Mayo Clin Proc Innov Qual Outcomes. 2023 Oct 10;7(5):499-513. doi: 10.1016/j.mayocpiqo.2023.09.001. PMID: 37859995; PMCID: PMC10582279.\u003c/li\u003e\n\u003cli\u003eKumar NR, Karanam VC, Kumar S, Kumar SD. Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection. South Med J. 2023 May;116(5):427-433. doi: 10.14423/SMJ.0000000000001546. PMID: 37137479; PMCID: PMC10143395.\u003c/li\u003e\n\u003cli\u003eMihalek N, Radovanović D, Barak O, Čolović P, Huber M, Erdoes G. Convalescent plasma and all-cause mortality of COVID-19 patients: systematic review and meta-analysis. Sci Rep. 2023 Aug 9;13(1):12904. doi: 10.1038/s41598-023-40009-8. PMID: 37558729; PMCID: PMC10412555.\u003c/li\u003e\n\u003cli\u003eHakim SM, Chikhouni GMA, Ammar MA, Amer AM. Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis. J Anesth. 2023 Jun;37(3):451-464. doi: 10.1007/s00540-023-03171-x. Epub 2023 Feb 22. PMID: 36811668; PMCID: PMC9944423.\u003c/li\u003e\n\u003cli\u003eIannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6. PMID: 37162745; PMCID: PMC10171886.\u003c/li\u003e\n\u003cli\u003eCasadevall A, Joyner MJ, Pirofski LA, Senefeld JW, Shoham S, Sullivan D, Paneth N, Focosi D. Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy. Expert Rev Respir Med. 2023 May;17(5):381-395. doi: 10.1080/17476348.2023.2208349. Epub 2023 May 2. PMID: 37129285.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"King Saud Medical City","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Covid-19, Passive immunization, Convalescent plasma","lastPublishedDoi":"10.21203/rs.3.rs-3911163/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3911163/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and aim:\u003c/h2\u003e \u003cp\u003eConvalescent plasma (CP) was early and successfully used in management of covid-19 infection. This report aimed to document our experience with use of CP in two critically-ill covid-19 patients.\u003c/p\u003e\u003ch2\u003eMain findings:\u003c/h2\u003e \u003cp\u003ePatients presented with fever, dry cough and difficulty of breathing with reduced oxygen saturation, massive radiological lung involvement and deteriorated Sequential Organ Failure Assessment (SOFA) Score. Use of two sessions of CP resulted in marked improvement of radiological and/or pulmonary findings. Both patients died of septic shock or thromboembolic events.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eUse of CP may be associated with radiological and clinical improvement in critically-ill patients. However, it\u0026rsquo;s not related to better survival if used in late stages of the disease.\u003c/p\u003e","manuscriptTitle":"Convalescent Plasma for Critically-ill Covid-19 Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-02 15:06:17","doi":"10.21203/rs.3.rs-3911163/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c54484e2-eaac-4c96-a3de-3a8ea8579828","owner":[],"postedDate":"February 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28464824,"name":"Internal Medicine"}],"tags":[],"updatedAt":"2024-02-02T15:06:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-02 15:06:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3911163","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3911163","identity":"rs-3911163","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2024) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-23T02:00:01.238055+00:00
License: CC-BY-4.0