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 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.

scholarly journals Safety and Immunogenicity Evaluation of Inactivated whole-virus-SARS-COV-2 As Emerging Vaccine Development In Egypt

2021 ◽  
Author(s):  
Amani A. Saleh ◽  
Mohamed A. Saad ◽  
Islam Ryan ◽  
Magdy Amin ◽  
Mohamed I. Shindy ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Neutralizing Antibody ◽  
Positive Development ◽  
Virus Challenge ◽  
Cell Monolayers ◽  
Transmission Electron ◽  
Dose Concentration ◽  
Antibody Titers

AbstractThe current worldwide pandemic COVID-19 is causing severe human health problems, with high numbers of mortality rates and huge economic burdens that require an urgent demand for safe, and effective and vaccine development. Our study was the first trail to development and evaluation of safety and immune response to inactivated whole SARS-COV-2 virus vaccine adjuvanted with aluminium hydroxide. We used characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069 and MW250352 at GenBank that isolated from Egyptian patients SARS-CoV-2-positive. Development of the vaccine was carried out in a BSL - 3 facilities and the immunogenicity was determined in mice at two doses (55µg and 100µg per dose). All vaccinated mice were received a booster dose 14 days post first immunization. Our results demonstrated distinct cytopathic effect on the vero cell monolayers induced through SARS-COV-2 propagation and the viral particles were identified as Coronaviridae by transmission electron microscopy. SARS-CoV-2 was identified by RT-PCR performed on the cell culture. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless the dose concentration, with excellent safety profiles.However, no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by wild virus challenge the vaccinated mice and detection of viral replication in lung tissues. Vaccinated mice recorded complete protection from challenge infection three weeks post second dose. SARS-COV-2 replication was not observed in the lungs of mice following SARS-CoV-2 challenge, regardless of the level of serum neutralizing antibodies. This finding will support the future trials for evaluation an applicable SARS-CoV-2 vaccine candidate.

scholarly journals Pathogenicity of Seneca Valley virus in pigs and detection in Culicoides from an infected pig farm

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jinyong Zhang ◽  
Chenghui Li ◽  
Yuan Meng ◽  
Yubiao Xie ◽  
Ning Shi ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Neutralizing Antibody ◽  
Antibody Titers ◽  
Pig Farm ◽  
Seneca Valley Virus ◽  
Set Up ◽  
Almost All ◽  
And Control ◽  
Virus Distribution

Abstract Background Porcine vesicular disease is caused by the Seneca Valley virus (SVV), it is a novel Picornaviridae, which is prevalent in several countries. However, the pathogenicity of SVV on 5–6 week old pigs and the transmission routes of SVV remain unknown. Methods This research mainly focuses on the pathogenicity of the CH-GX-01-2019 strain and the possible vector of SVV. In this study, 5–6 week old pigs infected with SVV (CH-GX-01-2019) and its clinical symptoms (including rectal temperatures and other clinical symptoms) were monitored, qRT-PCR were used to detect the viremia and virus distribution. Neutralization antibody assay was set up during this research. Mosquitoes and Culicoides were collected from pigsties after pigs challenge with SVV, and SVV detection within mosquitoes and Culicoides was done via RT-PCR. Results The challenged pigs presented with low fevers and mild lethargy on 5–8 days post infection. The viremia lasted more than 14 days. SVV was detected in almost all tissues on the 14th day following the challenge, and it was significantly higher in the hoofs (vesicles) and lymph nodes in comparison with other tissues. Neutralizing antibodies were also detected and could persist for more than 28 days, in addition neutralizing antibody titers ranged from 1:128 to 1:512. Mosquitoes and Culicoides were collected from the pigsty environments following SVV infection. Although SVV was not detected in the mosquitoes, it was present in the Culicoides, however SVV could not be isolated from the positive Culicoides. Conclusions Our work has enriched the knowledge relating to SVV pathogenicity and possible transmission routes, which may lay the foundation for further research into the prevention and control of this virus.

scholarly journals Receptor-Binding Domain Proteins of SARS-CoV-2 Variants Elicited Robust Antibody Responses Cross-Reacting with Wild-Type and Mutant Viruses in Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1383
Author(s):  
Juan Shi ◽  
Xiaoxiao Jin ◽  
Yan Ding ◽  
Xiaotao Liu ◽  
Anran Shen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Polyclonal Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Neutralization Capacity ◽  
Antibody Titers ◽  
High Level

Multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have spread around the world, but the neutralizing effects of antibodies induced by the existing vaccines have declined, which highlights the importance of developing vaccines against mutant virus strains. In this study, nine receptor-binding domain (RBD) proteins of the SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1 lineages) were constructed and fused with the Fc fragment of human IgG (RBD-Fc). These RBD-Fc proteins contained single or multiple amino acid substitutions at prevalent mutation points of spike protein, which enabled them to bind strongly to the polyclonal antibodies specific for wild-type RBD and to the recombinant human ACE2 protein. In the BALB/c, mice were immunized with the wild-type RBD-Fc protein first and boosted twice with the indicated mutant RBD-Fc proteins later. All mutant RBD-Fc proteins elicited high-level IgG antibodies and cross-neutralizing antibodies. The RBD-Fc proteins with multiple substitutions tended to induce higher antibody titers and neutralizing-antibody titers than the single-mutant RBD-Fc proteins. Meanwhile, both wild-type RBD-Fc protein and mutant RBD-Fc proteins induced significantly decreased neutralization capacity to the pseudovirus of B.1.351 and P.1 lineages than to the wild-type one. These data will facilitate the design and development of RBD-based subunit vaccines against SARS-COV-2 and its variants.

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 Pathogenicity of Seneca Valley virus in Pigs and Detection in Culicoides from an Infected Pig Farm

2021 ◽  
Author(s):  
Jinyong Zhang ◽  
Chenghui Li ◽  
Yuan Meng ◽  
Yubiao Xie ◽  
Ning Shi ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Neutralizing Antibody ◽  
Antibody Titers ◽  
Pig Farm ◽  
Seneca Valley Virus ◽  
Set Up ◽  
Almost All ◽  
And Control ◽  
Virus Distribution

Abstract Background: Porcine vesicular disease is caused by the Seneca Valley virus (SVV), it is a novel Picornaviridae, which is prevalent in several countries. However, the pathogenicity of SVV on 5-6 week old pigs and the transmission routes of SVV remain unknown.Methods: This research mainly focuses on the pathogenicity of the CH-GX-01-2019 strain and the possible vector of SVV. In this study, 5-6 week old pigs infected with SVV (CH-GX-01-2019) and its clinical symptoms (including rectal temperatures and other clinical symptoms) were monitored, qRT-PCR were used to detect the viremia and virus distribution. Neutralization antibody assay was set up during this research. Mosquitoes and Culicoides were collected from pigsties after pigs challenge with SVV, and SVV detection within mosquitoes and Culicoides was done via RT-PCR.Results: The challenged pigs presented with low fevers and mild lethargy on 5-8 days post infection (dpi). The viremia lasted more than 14 days. SVV was detected in almost all tissues on the 14th day following the challenge, and it was significantly higher in the hoofs (vesicles) and lymph nodes in comparison with other tissues. Neutralizing antibodies were also detected and could persist for more than 28 days, in addition neutralizing antibody titers ranged from 1:128 to 1:512. Mosquitoes and Culicoides were collected from the pigsty environments following SVV infection. Although SVV was not detected in the mosquitoes, it was present in the Culicoides, however SVV could not be isolated from the positive Culicoides. Conclusions: Our work has enriched the knowledge relating to SVV pathogenicity and possible transmission routes, which may lay the foundation for further research into the prevention and control of this virus.

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 LESSONS AND NEW PERSPECTIVES: IS CONVALESCENT PLASMA THERAPY EFFECTIVE ON COVID-19 PATIENTS?

2022 ◽  
pp. 50-57
Author(s):  
HERNITA TAURUSTYA ◽  
SRI YUNITA ◽  
YSRAFIL YSRAFIL ◽  
NUKE PRATIWI ◽  
ANINDITA RAHMATIAH
Keyword(s):  
Length Of Stay ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Neutralizing Antibody ◽  
Cochrane Collaboration ◽  
Disease Course ◽  
Journal Articles ◽  
Plasma Therapy ◽  
Contagious Diseases ◽  
Reduction Of Mortality

Objective: Recently, convalescent plasma (CP) therapy has shown promising evidence in the treatment of several serious contagious diseases, including SARS-CoV, Influenza and Ebola. We conducted a systematic review to extract data about using CP treatment for COVID-19 patients and it’s effectively. Methods: The retrieval of studies was conducted according to Cochrane Collaboration and from electronic databases including PubMed, Medline, and others (medRxiv and BioRxiv). Searching of the available evidence concerning CP treatment of COVID-19 patients was conducted in journal articles published between December 2019 and October 2020. The articles were further screened based on inclusion and exclusion criteria to identify the high-quality studies for analysis. Results: A total of 18 CP studies were included in this review. We found variance regarding the effectiveness of CP in the reduction of mortality rate, length of stay, and increased discharging rate. Several findings show CP therapy is effective in increasing viral negativity, neutralizing antibodies to recipients, does not cause harmful adverse reactions and in some cases can improve clinical symptoms. This therapy is presently considered effective for generating good clinical outcomes when given early in the course of the disease. Conclusion: The effectiveness of CP in terms of mortality, length of stay, and increased discharging patients is still debatable. However, CP therapy is effective in increasing the negativity of SARS-CoV-2 test, neutralizing antibody titer and is safe so it can be considered for COVID-19 patients. CP should not be given in the initial disease course but is recommended for the early disease course.

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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