scholarly journals An Old Therapy, Convalescent Plasma, for Coronavirus Disease-19: Do We Have All the Answer?

2020 ◽  
Vol 8 (T1) ◽  
pp. 530-537
Author(s):  
Ahmad Faried ◽  
Wahyu Widowati ◽  
Ruswana Anwar ◽  
Nucki Nursjamsi Hidajat ◽  
Ali Budi Harsono ◽  
...  
Keyword(s):  
Clinical Study ◽  
Healthcare Workers ◽  
Specific Treatment ◽  
Neutralizing Antibody ◽  
Alternative Therapies ◽  
Potential Candidate ◽  
Plasma Therapy ◽  
Current State ◽  
Antibody Titers ◽  
Review Current

BACKGROUND: Coronavirus (CoV) disease (COVID-19) has become a global health pandemic by early 2020; it has pushed the health-care system to its limit. From the initial estimates, 15% of COVID-19 patients caused by severe acute respiratory CoV 2 syndrome present with severe symptoms and requires hospitalization or even intensive care. There is no specific treatment against COVID-19, particularly for those with severe symptoms. Desperation caused by COVID-19 has driven clinicians to try an alternative therapies with little or even no-evidence previously. Convalescent plasma therapy (CPT) has emerged as a promising COVID-19 therapy. AIM: We aimed to review current state of convalescent plasma therapy. METHODS: We summarize the historical CPT, COVID-19 pathology and evaluate potential of CPT for COVID-19; raising the question regarding routinely administrating CPT to the COVID-19 patients, whether it is safe and effective. RESULTS: From cases in Indonesia and other countries, there is bunch of examples that healthcare workers being negatively stigmatized in case of COVID-19. They lost their rights to have a normal life in this pandemic era. A reasonable basis is found in many literatures to advocate the CPT. Convalescent plasma from COVID-19 patients who had been recovered with high neutralizing antibody titers was reported to be effective on transfusion to other COVID-19 patients. CONCLUSION: CPT is one good option to treat COVID-19 patients, but it not without risk; many potential candidate treatment that promising in theory but somehow fall apart when translated into clinical study; only time will tell, including our ongoing CPT clinical study.

scholarly journals Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of mild COVID-19 patients: sensitivity, specificity and association with virus neutralization test

2020 ◽  
Author(s):  
Antonin Bal ◽  
Bruno Pozzetto ◽  
Mary-Anne Trabaud ◽  
Vanessa Escuret ◽  
Muriel Rabilloud ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Virus Neutralization Test ◽  
Virus Neutralization ◽  
Serological Tests ◽  
Course Of Disease ◽  
Antibody Titers ◽  
Sensitivity Specificity

BackgroundThe association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild COVID-19 patients.MethodsA total of 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The sensitivity (determined weekly) of nine commercial serological assays were evaluated. Specificity was assessed using 69 pre-pandemic sera. Correlation, agreement and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at several neutralizing antibody titers.ResultsThe Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3 (78.1-96.1) and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG and DiaSorin, respectively. None of commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC<0.76).ConclusionsAlthough some assays presented a better agreement with VNT than others, the present findings emphasize that commercialized serological tests including those targeting the RBD cannot substitute a VNT for the assessment of functional antibody response.

scholarly journals The feasibility of convalescent plasma therapy in severe COVID- 19 patients: a pilot study

2020 ◽  
Author(s):  
Kai Duan ◽  
Bende Liu ◽  
Cesheng Li ◽  
Huajun Zhang ◽  
Ting Yu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Antiviral Agents ◽  
Neutralizing Antibody ◽  
Optimal Dose ◽  
Plasma Therapy ◽  
Reactive Protein ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
High Level

AbstractCurrently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65×109/L vs. 0.76×109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.Significance StatementCOVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explored the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was welltolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 days. Radiological examination showed varying degrees of absorption of lung lesions within 7 days. These results indicate that CP can serve as a promising rescue option for severe COVID-19 while the randomized trial is warranted.

scholarly journals Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)

2021 ◽  
Author(s):  
Daniel J. Sheward ◽  
Changil Kim ◽  
Roy A. Ehling ◽  
Alec Pankow ◽  
Xaquin Castro Dopico ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Blood Donors ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Pseudotyped Virus ◽  
Virus Neutralization Assay ◽  
Form Part ◽  
Antibody Titers ◽  
Cross Neutralization

The recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in many countries, with a spike that is highly diverged from the pandemic founder, raising fears that it may evade neutralizing antibody responses. We cloned the Omicron spike from a diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus neutralization assay, sharing initial neutralization results only 13 days after the variant was first reported to the WHO, 8 days after receiving the sample. Here we show that Omicron is substantially resistant to neutralization by several monoclonal antibodies that form part of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference sera sampled shortly after infection or vaccination are substantially less potent against Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, neutralization of Omicron was low to undetectable. However, in recent samples from two cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to the pandemic founder variant, and some donors showing no loss at all. A similar pattern was observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing antibody responses by the Omicron variant, and suggest that increasing the magnitude of neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise titers to levels that are protective.

scholarly journals High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

2020 ◽  
Author(s):  
Maria G. Noval ◽  
Maria E. Kaczmarek ◽  
Akiko Koide ◽  
Bruno A. Rodriguez-Rodriguez ◽  
Ping Louie ◽  
...  
Keyword(s):  
Antibody Response ◽  
Receptor Binding ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Pseudotyped Virus ◽  
Receptor Binding Domain ◽  
Neutralization Capacity ◽  
Antibody Isotypes ◽  
Antibody Titers

AbstractUnderstanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Here, we determine the ability of sera from 101 recovered healthcare workers to neutralize both authentic SARS-CoV-2 and SARS-CoV-2 pseudotyped virus and address their antibody titers against SARS-CoV-2 nucleoprotein and spike receptor-binding domain. Interestingly, the majority of individuals have low neutralization capacity and only 6% of the healthcare workers showed high neutralizing titers against both authentic SARS-CoV-2 virus and the pseudotyped virus. We found the antibody response to SARS-CoV-2 infection generates antigen-specific isotypes as well as a diverse combination of antibody isotypes, with high titers of IgG, IgM and IgA against both antigens correlating with neutralization capacity. Importantly, we found that neutralization correlated with antibody titers as quantified by ELISA. This suggests that an ELISA assay can be used to determine seroneutralization potential. Altogether, our work provides a snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides evidence that possessing multiple antibody isotypes may play an important role in SARS-CoV-2 neutralization.

scholarly journals Transition of antibody titers after the SARS-CoV-2 mRNA vaccine in Japanese healthcare workers

2021 ◽  
Author(s):  
Masahiro Kitabatake ◽  
Noriko Ouji-Sageshima ◽  
Shota Sonobe ◽  
Ryutaro Furukawa ◽  
Makiko Konda ◽  
...  
Keyword(s):  
Health Care Workers ◽  
Messenger Rna ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
Post Vaccination ◽  
The Third ◽  
Care Workers ◽  
Antibody Titers ◽  
Support Decision Making

AbstractSince February 2021, health care workers in Japan have been preferentially vaccinated with a messenger RNA vaccine (BNT162b2/Pfizer) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While many studies have confirmed that this vaccine is highly effective in reducing hospitalizations and deaths from coronavirus disease 2019 (COVID-19), antibody titers tend to decline at 3 months, leading to a risk of breakthrough infections. Thus, information is needed to support decision making regarding the third vaccination. In this study, we investigated transition of the anti-SARS-CoV-2 receptor-binding domain (RBD) IgG and neutralizing antibody titers of 41 vaccinated Japanese healthcare workers. Samples were collected seven times starting 1 week before vaccination until 6 months post-vaccination. Anti-SARS-CoV-2 RBD IgG levels peaked at 7 days after the booster, then declined over time and decreased to <10% at 6 months after the booster. Workers with low anti-SARS-CoV-2 RBD IgG levels also had low neutralizing antibody titers. These data support the active use of boosters for healthcare workers, especially for those with low anti-SARS-CoV-2 RBD IgG levels.

scholarly journals Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy

2021 ◽  
Vol 10 (4) ◽  
pp. 893
Author(s):  
Miguel Mateu-Sanz ◽  
Juan Tornín ◽  
Maria-Pau Ginebra ◽  
Cristina Canal
Keyword(s):  
Oxidative Stress ◽  
Atmospheric Plasma ◽  
Plasma Therapy ◽  
Primary Bone Tumor ◽  
Current State ◽  
Atmospheric Plasmas ◽  
New Strategy ◽  
Primary Bone ◽  
Stress Dependent ◽  
Review Current

Osteosarcoma is the most common primary bone tumor, and its first line of treatment presents a high failure rate. The 5-year survival for children and teenagers with osteosarcoma is 70% (if diagnosed before it has metastasized) or 20% (if spread at the time of diagnosis), stressing the need for novel therapies. Recently, cold atmospheric plasmas (ionized gases consisting of UV–Vis radiation, electromagnetic fields and a great variety of reactive species) and plasma-treated liquids have been shown to have the potential to selectively eliminate cancer cells in different tumors through an oxidative stress-dependent mechanism. In this work, we review the current state of the art in cold plasma therapy for osteosarcoma. Specifically, we emphasize the mechanisms unveiled thus far regarding the action of plasmas on osteosarcoma. Finally, we review current and potential future approaches, emphasizing the most critical challenges for the development of osteosarcoma therapies based on this emerging technique.

scholarly journals INVESTIGATIVE THERAPY OF COVID-19 CASES WITH CONVALESCENT PLASMA

2021 ◽  
pp. 1-3
Author(s):  
Anjan Jyoti Talukdar ◽  
Raj Pratim Das ◽  
Basanta Hazarika ◽  
Priyam Saikia ◽  
Tirtha Chaliha ◽  
...  
Keyword(s):  
Observational Study ◽  
Neutralizing Antibody ◽  
Supplemental Oxygen ◽  
Therapeutic Agents ◽  
Rt Pcr ◽  
Plasma Therapy ◽  
Clinical Benefits ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Pcr Test

BACKGROUD:Covid-19hasemergedhasanalarmingpublichealthcrisis,puttingthehealthcarefacilitiesacross theglobeat strain.Even after almost ten months of its identification,there exists only a few specific approved therapeutic agents for novel coronavirus disease.In this observational study,we have looked for any clinical benefits of convalescent plasma therapy in moderately severe cases of Covid-19,when added to a regimen consisting of Remdesivir,Dexamethasone and Heparin. METHODOLOGY: 528 moderately severe patients confirmed by RT-PCR test were enrolled. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to 268 patients as an addition to maximal supportive care and Remdesivir with steroid and heparin while 260 receivedRemdesivir with steroid and heparin. RESULTS:Theprimaryendpointwasmortalitybenefit.Thesecondendpointswerethereductionindaysofhospitalization,viral clearanceandimprovementofclinical symptoms.Themediantimefromonsetofillness toplasmatransfusionwas9.55d(range 6-24d).Nosevereadverseeffectswereobserved. CONCLUSION:Our studyshowedthatCPTcouldimprovesurvivalinpatientswhenaddedtothestandardtherapyinpatients with moderate Covid-19 infection. The add on therapy also significantly reduced the need for supplemental oxygen in the survivorsItcouldpotentiallyimprovetheclinicaloutcomesbesidesbeingawell-toleratedmodalityoftreatment.

scholarly journals A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

2021 ◽  
Author(s):  
Bastian Fischer ◽  
Christoph Lichtenberg ◽  
Lisa Mueller ◽  
Joerg Timm ◽  
Johannes Fischer ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Plasma Samples ◽  
Plasma Therapy ◽  
Antibody Titers ◽  
Combined Strategy ◽  
Common Cell

The determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories. Our data reveal the suitability of a novel ELISA-based surrogate virus neutralization test (sVNT) to easily measure the inhibition-capability of NAbs in the plasma of COVID-19 convalescents. We propose a combined strategy to detect plasma samples with high NAb titers (≥ 1:160) reliably and to, simultaneously, reduce the risk of erroneously identifying low-titer specimens. For this approach, results of the sVNT assay are compared to and combined with those acquired from the Euroimmun anti-SARS-CoV-2 IgG assay. Both assays are appropriate for high-throughput screening in standard BSL-2 laboratories. Our measurements further show a long-lasting humoral immunity of at least 11 months after symptom onset.

scholarly journals Use of convalescent serum reduces severity of COVID-19 in nonhuman primates

2020 ◽  
Author(s):  
Robert W. Cross ◽  
Abhishek N. Prasad ◽  
Viktoriya Borisevich ◽  
Courtney Woolsey ◽  
Krystle N. Agans ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Early Stage ◽  
Neutralizing Antibody ◽  
Plasma Therapy ◽  
Monkey Model ◽  
Inflammatory Processes ◽  
Antibody Titers ◽  
Lower Titer ◽  
High Level ◽  
Lesion Severity

AbstractPassive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against SARS-CoV-2 is currently being used to treat COVID-19 patients. However, most patients have been treated outside of randomized clinical trials making it difficult to determine the efficacy of this approach. Here, we assessed the efficacy of convalescent sera in a newly developed African green monkey model of COVID-19. Groups of SARS-CoV-2-infected animals were treated with pooled convalescent sera containing either high or low to moderate anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and disease pathology were minimal between monkeys that received the lower titer convalescent sera and untreated controls. However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Our data support human studies suggesting that convalescent plasma therapy is an effective strategy if donors with high level of antibodies against SARS-CoV-2 are employed and if recipients are at an early stage of disease.

scholarly journals Effectiveness of convalescent plasma therapy in severe COVID-19 patients

2020 ◽  
Vol 117 (17) ◽  
pp. 9490-9496 ◽  
Author(s):  
Kai Duan ◽  
Bende Liu ◽  
Cesheng Li ◽  
Huajun Zhang ◽  
Ting Yu ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Antiviral Agents ◽  
Neutralizing Antibody ◽  
Optimal Dose ◽  
Plasma Therapy ◽  
Oxyhemoglobin Saturation ◽  
Reactive Protein ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
High Level

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

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