Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 24
Filter
1.
Clin Infect Dis ; 74(2): 327-334, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1662105

ABSTRACT

Convalescent plasma (CP) have been used for treatment of coronavirus disease 2019 (COVID-19), but their effectiveness varies significantly. Moreover, the impact of CP treatment on the composition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 patients and antibody markers that differentiate between those who survive and those who succumb to the COVID-19 disease are not well understood. Herein, we performed longitudinal analysis of antibody profile on 115 sequential plasma samples from 16 hospitalized COVID-19 patients treated with either CP or standard of care, only half of them survived. Differential antibody kinetics was observed for antibody binding, immunoglobulin M/immunoglobulin G/immunoglobulin A (IgM/IgG/IgA) distribution, and affinity maturation in "survived" versus "fatal" COVID-19 patients. Surprisingly, CP treatment did not predict survival. Strikingly, marked decline in neutralization titers was observed in the fatal patients prior to death, and convalescent plasma treatment did not reverse this trend. Furthermore, irrespective of CP treatment, higher antibody affinity to the SARS-CoV-2 prefusion spike was associated with survival outcome. Additionally, sustained elevated IgA response was associated with fatal outcome in these COVID-19 patients. These findings propose that treatment of COVID-19 patients with convalescent plasma should be carefully targeted, and effectiveness of treatment may depend on the clinical and immunological status of COVID-19 patients, as well as the quality of the antibodies in the convalescent plasma.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive
2.
PLoS Pathog ; 17(1): e1009161, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388959

ABSTRACT

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.


Subject(s)
COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation , Argentina/epidemiology , COVID-19/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
3.
Hemodial Int ; 25(4): 515-522, 2021 10.
Article in English | MEDLINE | ID: covidwho-1270837

ABSTRACT

BACKGROUND: The passive immunization of patients with SARS-CoV2 with convalescent plasma (CP) is theoretically beneficial in patients with end-stage renal disease who are immunosuppressed and unable to mount an adequate immune response. Hence, this study was conducted to evaluate the safety and efficacy of CP in patients with chronic kidney disease on hemodialysis with moderate-to-severe SARS-CoV2 infection. METHODS: A prospective observational cohort study was conducted in consecutive 68 moderate-to-severe SARS-CoV2 infected patients who were on maintenance hemodialysis or with acute worsening of chronic kidney disease which required initiation of hemodialysis. Patients who received CP were compared with those who did not. The primary outcome was death during hospitalization. Clinical characteristics, duration of hospitalization and inflammatory parameters were compared between the two groups. A subgroup analysis was done to find whether early initiation of plasma was associated with better outcome. RESULTS: Sixteen patients (44%) in the plasma group and 14 (45%) patients in the control group died during hospitalization (p = 0.95). The median duration of hospitalization was 9 (6-14) days in the plasma group and 9 (6-16) in the control group (p = 0.60). There was no difference in mortality or duration of hospitalization with respect to early initiation of CP (p = 0.29). Fistula thrombosis occurred in two patients (11.1%) in the plasma group. CONCLUSION: Therapy with CP does not appear to confer any clinical benefit in moderate-to-severe SARS-CoV-2 infected patients with chronic kidney disease on hemodialysis.


Subject(s)
COVID-19 , RNA, Viral , COVID-19/therapy , Humans , Immunization, Passive , Prospective Studies , Renal Dialysis/adverse effects , SARS-CoV-2 , Treatment Outcome
4.
Arch Pathol Lab Med ; 145(10): 1221-1227, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1261421

ABSTRACT

CONTEXT.­: The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has elicited a surge in demand for serologic testing to identify previously infected individuals. In particular, antibody testing is crucial in identifying COVID-19 convalescent plasma, which has been approved by the Food and Drug Administration under the Emergency Use Authorization for use as passive immunotherapy for hospitalized patients infected with COVID-19. Currently, high-titer COVID-19 convalescent plasma can be qualified by Ortho's Vitros COVID-19 IgG antibody test. OBJECTIVE.­: To explore the use of an efficient testing method to identify high-titer COVID-19 convalescent plasma for use in treating COVID-19-infected patients and track COVID-19 positivity over time. DESIGN.­: We evaluated an enzyme-linked immunosorbent assay (ELISA)-based method that detects antibodies specific to the SARS-CoV-2 receptor binding domain (RBD) with individual and pooled plasma samples and compared its performance against the Vitros COVID-19 IgG antibody test. Using the pooled RBD-ELISA (P-RE) method, we also screened more than 10 000 longitudinal healthy blood donor samples to assess seroprevalence. RESULTS.­: P-RE demonstrates 100% sensitivity in detecting Food and Drug Administration-defined high-titer samples when compared with the Vitros COVID-19 IgG antibody test. Overall sensitivity of P-RE when compared with the Vitros COVID-19 IgG antibody test and our individual sample RBD-ELISA (I-RE) were 83% and 56%, respectively. When screening 10 218 healthy blood donor samples by P-RE, we found the seroprevalence correlated with the local infection rates with a correlation coefficient of 0.21 (P < .001). CONCLUSIONS.­: Pooling plasma samples can be used to efficiently screen large populations for individuals with high-titer anti-RBD antibodies, important for COVID-19 convalescent plasma identification.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Blood Donors/statistics & numerical data , COVID-19/epidemiology , COVID-19/virology , Humans , Immunoglobulin G/blood , Pandemics/prevention & control , Reproducibility of Results , SARS-CoV-2/physiology , Sensitivity and Specificity , Seroepidemiologic Studies
5.
Nat Commun ; 12(1): 3189, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1246368

ABSTRACT

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , Cytokines/blood , SARS-CoV-2/immunology , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Donors , COVID-19/blood , COVID-19/virology , Disease Progression , Female , Hospitalization , Humans , Immunization, Passive , Immunoglobulin G/blood , Kaplan-Meier Estimate , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
6.
Front Immunol ; 12: 675679, 2021.
Article in English | MEDLINE | ID: covidwho-1231340

ABSTRACT

Background: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.


Subject(s)
Antibodies, Viral , Betacoronavirus/immunology , COVID-19/therapy , Common Cold/immunology , Convalescence , Coronavirus OC43, Human/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/administration & dosage , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/mortality , Cross Reactions , Female , Humans , Immunization, Passive , Male , Middle Aged
7.
PLoS One ; 16(5): e0251262, 2021.
Article in English | MEDLINE | ID: covidwho-1221859

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic overwhelmed healthcare systems, highlighting the need to better understand predictors of mortality and the impact of medical interventions. METHODS: This retrospective cohort study examined data from every patient who tested positive for COVID-19 and was admitted to White Plains Hospital between March 9, 2020, and June 3, 2020. We used binomial logistic regression to analyze data for all patients, and propensity score matching for those treated with hydroxychloroquine and convalescent plasma (CP). The primary outcome of interest was inpatient mortality. RESULTS: 1,108 admitted patients with COVID-19 were available for analysis, of which 124 (11.2%) were excluded due to incomplete data. Of the 984 patients included, 225 (22.9%) died. Risk for death decreased for each day later a patient was admitted [OR 0.970, CI 0.955 to 0.985; p < 0.001]. Elevated initial C-reactive protein (CRP) value was associated with a higher risk for death at 96 hours [OR 1.007, 1.002 to 1.012; p = 0.006]. Hydroxychloroquine and CP administration were each associated with increased mortality [OR 3.4, CI 1.614 to 7.396; p = 0.002, OR 2.8560, CI 1.361 to 6.160; p = 0.006 respectively]. CONCLUSIONS: Elevated CRP carried significant odds of early death. Hydroxychloroquine and CP were each associated with higher risk for death, although CP was without titers and was administered at a median of five days from admission. Randomized or controlled studies will better describe the impact of CP. Mortality decreased as the pandemic progressed, suggesting that institutional capacity for dynamic evaluation of process and outcome measures may benefit COVID-19 survival.


Subject(s)
COVID-19/mortality , Hospital Mortality , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Logistic Models , Male , Middle Aged , Odds Ratio , Outcome Assessment, Health Care , Retrospective Studies , Risk , SARS-CoV-2/isolation & purification , Young Adult
9.
Clin Infect Dis ; 74(2): 327-334, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1189441

ABSTRACT

Convalescent plasma (CP) have been used for treatment of coronavirus disease 2019 (COVID-19), but their effectiveness varies significantly. Moreover, the impact of CP treatment on the composition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 patients and antibody markers that differentiate between those who survive and those who succumb to the COVID-19 disease are not well understood. Herein, we performed longitudinal analysis of antibody profile on 115 sequential plasma samples from 16 hospitalized COVID-19 patients treated with either CP or standard of care, only half of them survived. Differential antibody kinetics was observed for antibody binding, immunoglobulin M/immunoglobulin G/immunoglobulin A (IgM/IgG/IgA) distribution, and affinity maturation in "survived" versus "fatal" COVID-19 patients. Surprisingly, CP treatment did not predict survival. Strikingly, marked decline in neutralization titers was observed in the fatal patients prior to death, and convalescent plasma treatment did not reverse this trend. Furthermore, irrespective of CP treatment, higher antibody affinity to the SARS-CoV-2 prefusion spike was associated with survival outcome. Additionally, sustained elevated IgA response was associated with fatal outcome in these COVID-19 patients. These findings propose that treatment of COVID-19 patients with convalescent plasma should be carefully targeted, and effectiveness of treatment may depend on the clinical and immunological status of COVID-19 patients, as well as the quality of the antibodies in the convalescent plasma.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive
10.
Clin Immunol ; 227: 108723, 2021 06.
Article in English | MEDLINE | ID: covidwho-1171785

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 infected patients, receiving background anti-CD20 therapy, were treated with convalescent plasma or plasma-based products. Eight patients were included in the study, presenting with prolonged disease course and delayed viral clearance. CP/plasma-based products were offered as an add-on therapy to standard medical treatment. All patients showed remarkable clinical and laboratory improvement. In addition, polymerase chain reaction from nasopharyngeal swabs rapidly converted to negative following plasma administration. This study emphasizes the therapeutic efficacy of convalescent plasma and plasma-based products in a subgroup of immunocompromised patients with iatrogenic B-cell depletion.


Subject(s)
B-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/therapy , Immunocompromised Host/drug effects , SARS-CoV-2/drug effects , Antibodies, Viral/blood , Antineoplastic Agents, Immunological/administration & dosage , COVID-19/physiopathology , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , Rituximab/administration & dosage , Treatment Outcome
11.
Trials ; 22(1): 199, 2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1127723

ABSTRACT

BACKGROUND: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. METHODS: Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. DISCUSSION: This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.


Subject(s)
Antibodies, Neutralizing/therapeutic use , COVID-19/therapy , Immunoglobulin G/therapeutic use , Animals , Antibodies, Monoclonal, Humanized , Clinical Trials, Phase II as Topic , Double-Blind Method , Humans , Immunization, Passive , Oxygen Inhalation Therapy , Randomized Controlled Trials as Topic , SARS-CoV-2/immunology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Swine , Time Factors
13.
Allergy Asthma Clin Immunol ; 17(1): 14, 2021 Feb 05.
Article in English | MEDLINE | ID: covidwho-1067269

ABSTRACT

BACKGROUND: Common variable immunodeficiency is the most prevalent symptomatic primary immunodeficiency in adults. Affected patients fail to mount an appropriate humoral response against community acquired infectious diseases and recent reports have provided data supporting the increased susceptibility of these patients to severe SARS-CoV-2 infections. In this context, the infusion of COVID-19 convalescent plasma could represent an effective therapeutic strategy. CASE PRESENTATION: 25-year old woman diagnosed with common variable immunodeficiency in 2013, developed severe COVID-19 that rapidly progressed to pneumonia presenting with multiple bilateral lung opacities that were both central and peripheral and presented as ground-glass and consolidation types involving all lobes, bilaterally. As blood oxygen saturation decayed and lung abnormalities were not responsive to large spectrum antibiotics and corticosteroids, patient was placed on mechanical ventilation and compassionate-use of approved COVID-19 convalescent donor plasma was introduced. The patient presented a rapid response to the approach and mechanical ventilation could be interrupted 24 h after first dose of COVID-19 convalescent donor plasma. As a whole, the patient received four doses of 200 mL convalescent plasma during a period of 6 days. There was rapid improvement of clinical status, with interruption of supplemental oxygen therapy after 6 days and reduction of lung abnormalities as evidence by sequential computed tomography scans. CONCLUSIONS: This is a single patient report that adds to other few reports on common variable immunodeficiency and agammaglobulinemia, suggesting that COVID-19 convalescent donor plasma could be a valuable therapeutic approach to treat patients affected by dysgammaglobulinemias and presenting severe COVID-19.

14.
Trials ; 22(1): 70, 2021 Jan 20.
Article in English | MEDLINE | ID: covidwho-1067258

ABSTRACT

BACKGROUND: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. METHODS/DESIGN: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345523 . Registered on 30 March, 2020. First posted date: April 14, 2020.


Subject(s)
COVID-19/therapy , SARS-CoV-2/isolation & purification , Adult , COVID-19/diagnosis , Clinical Trials, Phase II as Topic , Female , Hospitalization , Humans , Immunization, Passive/adverse effects , Male , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Severity of Illness Index , Standard of Care , Treatment Outcome
15.
Int J Infect Dis ; 102: 332-334, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060485

ABSTRACT

The pathophysiology of severe coronavirus disease 2019 (COVID-19) is primarily a host immune interplay to virus invasion. The therapeutic options have been explored either against hyperinflammation from dysregulated adaptive immunity or direct virus neutralization using antibodies from convalescent plasma (CP) of a recovered patient. The therapeutic plasma exchange (TPE) for removal of excessive inflammatory cytokines has been tried with success in COVID-19. We undertook this exploratory study to evaluate safety and efficacy of TPE followed by CP transfusion in 14 patients with critical COVID-19 requiring invasive mechanical ventilation (IMV). All patients showed improvement in symptoms and decrease of inflammatory markers especially CRP (p = 0.03). 10 patients were liberated from IMV after a median of 5.5 (3-36) days, post sequential therapy. Day 7 and Day 28 mortality was 21.4% and 28.6% respectively. The median duration ICU and hospital LOS were 12 (5-42) days and 18 (12-47) days respectively. No patient developed transfusion-associated complications, but three patients developed secondary bacterial sepsis within 14 days of therapy, and one died. This case series demonstrated the sequential use of TPE followed by CP transfusion as a therapeutic option in critical COVID-19.


Subject(s)
Blood Component Transfusion , COVID-19/therapy , Plasma Exchange , Adult , Aged , COVID-19/immunology , COVID-19/mortality , Female , Humans , Immunization, Passive , Male , Middle Aged , Plasma/immunology , SARS-CoV-2/immunology
16.
J Infect Chemother ; 27(4): 653-655, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1032960

ABSTRACT

INTRODUCTION: Convalescent plasma transfusion (CPT), a potential therapy for coronavirus disease 2019 (COVID-19), requires strict quality control of the donor blood. Whether to confirm the disappearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA (RNAemia) in convalescent donor blood or not is unclear. Reports recommending the proof of viral disappearance from the blood are controversial. Foreseeing CPT in treating COVID-19 patients in Japan, we investigated RNAemia in 100 convalescent donors with mild, moderate, and severe COVID-19. METHODS: Between April 30 and July 30, 2020, we measured RNAemia in the plasma samples of donors with resolved COVID-19. Data on patients' demographics, comorbidities, pneumonia, treatment, and real-time polymerase chain reaction results for SARS-CoV-2 were collected. Date of onset of initial symptoms or date of positive testing (for asymptomatic patients) were self-reported by the patients. Disease severity was defined as: no, mild, moderate oxygen demand, or severe (requiring mechanical ventilation). RESULTS: Of 100 donors (58 males [58.0%]; median age, 47 [range 22-69] years) screened as of July 30, 2020, 77 (77.0%); 19 (19.0%); and 4 (4.0%) had mild, moderate, and severe disease, respectively. Median time between onset and testing was 68.5 (range, 21-167) days. SARS-CoV-2 RNA was not detected in any of the plasma samples. CONCLUSION: RNAemia was not found in recovered COVID-19 patients at least 21, 27, and 57 days after the onset of mild, moderate, and severe symptoms. Our study may contribute to determining a suitable time for collecting convalescent plasma from COVID-19 patients and to future CPT use.


Subject(s)
COVID-19/blood , COVID-19/therapy , RNA, Viral/blood , SARS-CoV-2 , Adult , Aged , Female , Humans , Immunization, Passive , Male , Middle Aged , Severity of Illness Index
17.
N Engl J Med ; 384(7): 610-618, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1012716

ABSTRACT

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).


Subject(s)
COVID-19/therapy , Immunoglobulin G/blood , Respiratory Insufficiency/prevention & control , SARS-CoV-2/immunology , Aged , Aged, 80 and over , Blood Component Transfusion , COVID-19/complications , Disease Progression , Double-Blind Method , Female , Humans , Immunization, Passive , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Respiratory Insufficiency/etiology , Severity of Illness Index
18.
J Zhejiang Univ Sci B ; 21(12): 955-960, 2020.
Article in English | MEDLINE | ID: covidwho-999889

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Adult , Aged , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19/therapy , China , Female , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged
19.
Sci China Life Sci ; 63(12): 1833-1849, 2020 12.
Article in English | MEDLINE | ID: covidwho-996429

ABSTRACT

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/therapeutic use , Asymptomatic Infections , COVID-19/prevention & control , COVID-19 Vaccines/isolation & purification , China , Drug Development/trends , Host Microbial Interactions/immunology , Humans , Immunity, Humoral , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Models, Immunological , Pandemics , Reinfection/immunology , Reinfection/prevention & control , Seroconversion
20.
PLoS One ; 15(12): e0243967, 2020.
Article in English | MEDLINE | ID: covidwho-992705

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2-6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100-1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , COVID-19/therapy , Adolescent , Adult , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Neutralization Tests , Pandemics , Plasma/immunology , Plasma/virology , Plasmapheresis/methods , SARS-CoV-2/immunology , Tissue Donors , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL