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

Author(s):  
HERNITA TAURUSTYA ◽  
SRI YUNITA ◽  
YSRAFIL YSRAFIL ◽  
NUKE PRATIWI ◽  
ANINDITA RAHMATIAH

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.

Author(s):  
Kai Duan ◽  
Bende Liu ◽  
Cesheng Li ◽  
Huajun Zhang ◽  
Ting Yu ◽  
...  

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.


Author(s):  
Shruti Vimal ◽  
Pratiksha Naval ◽  
Manoj Sawadker ◽  
Pallavi Bhomia ◽  
Neha Jadhav ◽  
...  

The recent pandemic due to Corona virus more popularly known as COVID 19 has reassessed the usefulness of historic convalescent plasma transfusion. (CPT) The CPT is one of the promising therapies in the current pandemic situation. This review was conducted to evaluate the effectiveness of CPT therapy in COVID 19 patients based on the publications reported till date. PubMed, EMBASE and Medline databases were screened up to 30 April 2021. All the records were screened as per the protocol eligibility criteria.  The main features of the studies reviewed were, convalescent plasma can reduce mortality in severely ill patients, an increase in neutralizing antibodies titre and disappearance of SARS CoV 2 RNA was observed in all the patients on CPT therapy and over all a beneficial effect on clinical symptoms after administration of CP.  Based on the review findings and the limited scientific data, CPT therapy in COVID 19 patients appear safe, clinically effective and reduces mortality. However, the need of a multicentre clinical trials, unequivocal proof of efficacy, effectiveness and the need for the standardisation of the CPT needs to be addressed immediately for the full utilisation of potential of CPT.


2021 ◽  
Author(s):  
Amani A. Saleh ◽  
Mohamed A. Saad ◽  
Islam Ryan ◽  
Magdy Amin ◽  
Mohamed I. Shindy ◽  
...  

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.


2020 ◽  
Author(s):  
Fiona Tea ◽  
Alberto Ospina Stella ◽  
Anupriya Aggarwal ◽  
David Ross Darley ◽  
Deepti Pilli ◽  
...  

AbstractThe SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of ‘high responders’ maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.One Sentence SummaryNeutralizing antibody responses to SARS-CoV-2 are sustained, associated with COVID19 severity, and evaded by emerging viral variants


2021 ◽  
Author(s):  
Amani A Saleh ◽  
Mohamed A Saad ◽  
Islam Ryan ◽  
Magdy Amin ◽  
Mohamed I Shindy ◽  
...  

Abstract Background Current worldwide pandemic COVID-19 with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 three weeks after the 2nd dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials. Methods 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 were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL—3 facilities and the immunogenicity was determined in mice at two doses (55 μg and 100 μg per dose). Results The distinct cytopathic effect (CPE) induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues. Conclusions Vaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.


Author(s):  
Antonio E. Muruato ◽  
Camila R. Fontes-Garfias ◽  
Ping Ren ◽  
Mariano A. Garcia-Blanco ◽  
Vineet D. Menachery ◽  
...  

AbstractVirus neutralization remains the gold standard for determining antibody efficacy. Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. Our approach offers a rapid platform that can be scaled to screen people for antibody protection from COVID-19, a key parameter necessary to safely reopen local communities.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jinyong Zhang ◽  
Chenghui Li ◽  
Yuan Meng ◽  
Yubiao Xie ◽  
Ning Shi ◽  
...  

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.


Author(s):  
Hao Zeng ◽  
Dongfang Wang ◽  
Jingmin Nie ◽  
Haoyu Liang ◽  
Jiang Gu ◽  
...  

Abstract Convalescent plasma (CP) transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections. However, the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019 (COVID-19). We aimed to explore the potential efficacy of CP therapy, and to assess the possible factors associated with its efficacy. We enrolled eight critical or severe COVID-19 patients from four centers. Each patient was transfused with 200–400 mL of CP from seven recovered donors. The primary indicators for clinical efficacy assessment were the changes of clinical symptoms, laboratory parameters, and radiological image after CP transfusion. CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody (NAb) level. No adverse events were observed during and after CP transfusion. Following CP transfusion, six out of eight patients showed improved oxygen support status; chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days; the viral load was decreased to a negative level in five patients who had the previous viremia; other laboratory parameters also tended to improve, including increased lymphocyte counts, decreased C-reactive protein, procalcitonin, and indicators for liver function. The clinical efficacy might be associated with CP transfusion time, transfused dose, and the NAb levels of CP. This study indicated that CP might be a potential therapy for severe patients with COVID-19.


Author(s):  
Purbita Bandopadhyay ◽  
Ranit D’Rozario ◽  
Abhishake Lahiri ◽  
Jafar Sarif ◽  
Yogiraj Ray ◽  
...  

SummaryTo characterize key components and dynamics of the cytokine storm associated with severe COVID-19 disease, we assessed abundance and correlative expression of a panel of forty eight cytokines in patients suffering from acute respiratory distress syndrome (ARDS), as compared to patients with mild disease. Then in a randomized control trial on convalescent plasma therapy (CPT) in COVID-19 ARDS, we analyzed the immediate effects of CPT on the dynamics of the cytokine storm as a correlate for the level of hypoxia experienced by the patients. Plasma level of monocyte chemotactic protein 3 was found to be a key correlate for clinical improvement, irrespective of therapy received. We also identified a hitherto unappreciated anti-inflammatory role of CPT independent of its neutralizing antibody content. Neutralizing antibodies as well as reductions in circulating interleukin-6 and interferon gamma induced protein 10, both contributed to marked immediate reductions in hypoxia in severe COVID-19 patients receiving CPT.Abstract Figure


2020 ◽  
Author(s):  
Douglas F. Lake ◽  
Alexa J. Roeder ◽  
Erin Kaleta ◽  
Paniz Jasbi ◽  
Sivakumar Periasamy ◽  
...  

As increasing numbers of people recover from and are vaccinated against COVID-19, tests are needed to measure levels of protective, neutralizing antibodies longitudinally to help determine duration of immunity. We developed a lateral flow assay (LFA) that measures levels of neutralizing antibodies in plasma, serum or whole blood. The LFA is based on the principle that neutralizing antibodies inhibit binding of the spike protein receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2). The test classifies high levels of neutralizing antibodies in sera that were titered using authentic SARS-CoV-2 and pseudotype neutralization assays with an accuracy of 98%. Sera obtained from patients with seasonal coronavirus did not prevent RBD from binding to ACE2. As a demonstration for convalescent plasma therapy, we measured conversion of non-immune plasma into strongly neutralizing plasma. This is the first report of a neutralizing antibody test that is rapid, highly portable and relatively inexpensive that might be useful in assessing COVID-19 vaccine immunity.


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