Treatment of severe COVID-19 with convalescent plasma in Bronx, NYC

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score–matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.

[1]  F. Polack,et al.  Prevention of severe COVID-19 in the elderly by early high-titer plasma therapy , 2021, The New England Journal of Medicine.

[2]  S. Zolla-Pazner,et al.  Role of IgM and IgA Antibodies in the Neutralization of SARS-CoV-2. , 2020, The Journal of infectious diseases.

[3]  L. Pirofski,et al.  Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis , 2020, ACS omega.

[4]  A. Tewari,et al.  Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial , 2020, medRxiv.

[5]  D. Follmann,et al.  A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia , 2020, The New England journal of medicine.

[6]  R. Olsen,et al.  Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG , 2020, The American Journal of Pathology.

[7]  R. Olsen,et al.  Significantly decreased mortality in a large cohort of COVID-19 patients transfused early with convalescent plasma containing high titer anti-SARS-CoV-2 spike protein IgG , 2020, The American Journal of Pathology.

[8]  D. Skovronsky,et al.  SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 , 2020, The New England journal of medicine.

[9]  C. Cordon-Cardo,et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months , 2020, Science.

[10]  T. Bhatnagar,et al.  Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial) , 2020, BMJ.

[11]  A. Iafrate,et al.  COVID-19 neutralizing antibodies predict disease severity and survival , 2020, medRxiv.

[12]  S. Greene,et al.  Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis , 2020, The Lancet Infectious Diseases.

[13]  B. Althouse,et al.  Clinical management and mortality among COVID-19 cases in sub-Saharan Africa: A retrospective study from Burkina Faso and simulated case analysis , 2020, International Journal of Infectious Diseases.

[14]  Nicole M. Bouvier,et al.  Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study , 2020, Nature Medicine.

[15]  L. Pirofski,et al.  Development, clinical translation, and utility of a COVID-19 antibody test with qualitative and quantitative readouts , 2020, medRxiv.

[16]  Arthur S Slutsky,et al.  Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. , 2020, JAMA.

[17]  J. Alcamí,et al.  Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial , 2020, medRxiv.

[18]  V. Fan,et al.  Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection , 2020, JAMA network open.

[19]  S. Smirnakis,et al.  Characteristics and Outcomes of Latinx Patients With COVID-19 in Comparison With Other Ethnic and Racial Groups , 2020, Open forum infectious diseases.

[20]  J. Bailey,et al.  Convalescent plasma for patients with severe COVID-19: a matched cohort study , 2020, medRxiv.

[21]  A. Casadevall,et al.  Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience , 2020, medRxiv.

[22]  S. Agarwal,et al.  Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19. , 2020, Journal of hospital medicine.

[23]  R. Feinman,et al.  Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma: a prospective study , 2020, medRxiv.

[24]  Jessica S. Brown,et al.  Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020. , 2020, MMWR. Morbidity and mortality weekly report.

[25]  Ryung S. Kim,et al.  The association of race and COVID-19 mortality , 2020, EClinicalMedicine.

[26]  Liyan Wen,et al.  Kinetics of viral load and antibody response in relation to COVID-19 severity. , 2020, The Journal of clinical investigation.

[27]  M. M. van der Eerden,et al.  Convalescent Plasma for COVID-19. A randomized clinical trial , 2020, medRxiv.

[28]  A. Abdulamir,et al.  The therapeutic effectiveness of Convalescent plasma therapy on treating COVID-19 patients residing in respiratory care units in hospitals in Baghdad, Iraq , 2020, medRxiv.

[29]  Jennifer L. Bell,et al.  Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report , 2020, medRxiv.

[30]  J. Pagel,et al.  Use of convalescent plasma in hospitalized patients with COVID-19: case series , 2020, Blood.

[31]  Patrick W. Johnson,et al.  Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. , 2020, The Journal of clinical investigation.

[32]  J. Dillner,et al.  A systematic review of convalescent plasma treatment for COVID19 , 2020, medRxiv.

[33]  L. Ren,et al.  Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. , 2020, JAMA.

[34]  Yajuan Li,et al.  Serum IgA, IgM, and IgG responses in COVID-19 , 2020, Cellular & Molecular Immunology.

[35]  S. W. Long,et al.  Treatment of COVID-19 Patients with Convalescent Plasma , 2020, The American Journal of Pathology.

[36]  L. Dodd,et al.  Remdesivir for the Treatment of Covid-19 — Final Report , 2020, The New England journal of medicine.

[37]  L. Pirofski,et al.  A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition , 2020, bioRxiv.

[38]  S. Szefler,et al.  COVID-19 and the impact of social determinants of health , 2020, The Lancet Respiratory Medicine.

[39]  Jonathan Ross,et al.  The Disproportionate Burden of COVID-19 for Immigrants in the Bronx, New York. , 2020, JAMA internal medicine.

[40]  Raj Bhopal,et al.  Sharpening the global focus on ethnicity and race in the time of COVID-19 , 2020, The Lancet.

[41]  Changyu Shen,et al.  Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs. , 2020, JAMA.

[42]  X. Tang,et al.  Antibody responses to SARS-CoV-2 in patients with COVID-19 , 2020, Nature Medicine.

[43]  V. Raabe,et al.  Current studies of convalescent plasma therapy for COVID-19 may underestimate risk of antibody-dependent enhancement , 2020, Journal of Clinical Virology.

[44]  Quanyi Wang,et al.  Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients , 2020, medRxiv.

[45]  T. Lv,et al.  Treatment with convalescent plasma for COVID‐19 patients in Wuhan, China , 2020, Journal of medical virology.

[46]  Y. Yazdanpanah,et al.  Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients , 2020, Emerging infectious diseases.

[47]  Yan Peng,et al.  Effectiveness of convalescent plasma therapy in severe COVID-19 patients , 2020, Proceedings of the National Academy of Sciences.

[48]  Y. Wen,et al.  Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications , 2020, medRxiv.

[49]  M. Fain,et al.  SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes , 2020, GeroScience.

[50]  Bin Zhang,et al.  Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection , 2020, Chest.

[51]  Y. Wen,et al.  Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications , 2020, medRxiv.

[52]  Jing Yuan,et al.  Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. , 2020, JAMA.

[53]  Hongming Miao,et al.  Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study , 2020, Signal Transduction and Targeted Therapy.

[54]  Ezekiel J Emanuel,et al.  Fair Allocation of Scarce Medical Resources in the Time of Covid-19. , 2020, The New England journal of medicine.

[55]  Arturo Casadevall,et al.  The convalescent sera option for containing COVID-19. , 2020, The Journal of clinical investigation.

[56]  A. M. Leontovich,et al.  The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 , 2020, Nature Microbiology.

[57]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[58]  Lei Liu,et al.  Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 , 2020, medRxiv.

[59]  Bo Diao,et al.  Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) , 2020, Frontiers in Immunology.

[60]  B. Graham,et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation , 2020, Science.

[61]  Su Hwan Lee,et al.  Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea , 2020, Journal of Korean medical science.

[62]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[63]  Jung-Han Kim,et al.  Stereotactic Core-Needle Biopsy of Non-Mass Calcifications: Outcome and Accuracy at Long-Term Follow-Up , 2003, Korean journal of radiology.

[64]  F. Hayden,et al.  Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia , 2016, Emerging infectious diseases.

[65]  W. Lim,et al.  The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis , 2014, The Journal of infectious diseases.

[66]  J. Peiris,et al.  Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent FcγR Pathway , 2011, Journal of Virology.

[67]  Kwok-Hung Chan,et al.  Convalescent Plasma Treatment Reduced Mortality in Patients With Severe Pandemic Influenza A (H1N1) 2009 Virus Infection , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[68]  Jake Bowers,et al.  Covariate balance in simple stratified and clustered comparative studies , 2008, 0808.3857.

[69]  S. Hoffman,et al.  Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment? , 2006, Annals of Internal Medicine.

[70]  P. Chan,et al.  Use of convalescent plasma therapy in SARS patients in Hong Kong , 2004, European Journal of Clinical Microbiology and Infectious Diseases.

[71]  V. Wong,et al.  Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients , 2004, Journal of Clinical Virology.