Convalescent plasma: A potential therapeutic option for COVID-19 patients

The new coronavirus disease(COVID-19)outbreak has challenged us to take unprecedented steps to bring this pandemic under control.In view of the urgency of this situation,convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic.This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes.In addition,on-going large clinical trials aimed to further evaluate the effectiveness,safety,and optimal dosage,duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results.Therefore,this article aims to provide an overview of possible mechanisms of actions of convalescent plasma,its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Background:Due to the outbreak and rapid spread of coronavirus disease 2019(COVID-19),more than 160 million patients have become convalescents worldwide to date.Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19.However,it is unknown whether their characteristics return to normal after the 1-year recovery.Methods:We recruited 35 confirmed patients to provide specimens at discharge and 1 year later,as well as 160healthy controls.A total of 497 samples were prospectively collected,including 219 tongue-coating,129 stool and 149 plasma samples.Tongue-coating and stool samples were subjected to 16S rRNA sequencing,and plasma samples were subjected to untargeted metabolomics testing.Results:The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal.In the recovery process,the microbial diversity gradually increased.Butyric acid-producing microbes and Bifidobacterium gradually increased,whereas lipopolysaccharideproducing microbes gradually decreased.In addition,sphingosine-1-phosphate,which is closely related to the inflammatory factor storm of COVID-19,increased significantly during the recovery process.Moreover,the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later.Conclusions:This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19.The key microbiome and metabolites in the process of recovery were identified,and provided new treatment ideas for accelerating recovery.And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Timing of convalescent plasma therapy-tips from curing a 100-yearold COVID-19 patient using convalescent plasma treatment: A case report

BACKGROUND Convalescent plasma therapy is used for the treatment of critically ill patients for newly discovered infectious diseases,such as coronavirus disease 2019(COVID-19)pneumonia,under the premise of lacking specific treatment drugs and corresponding vaccines.But the best timing application of plasma therapy and whether it is effective by antiviral and antibiotic treatment remain unclear.CASE SUMMARY We describe a patient with COVID-19,a 100-year-old,high-risk,elderly male who had multiple underlying diseases such as stage 2 hypertension(very high-risk group)and infectious pneumonia accompanied by chronic obstructive pulmonary disease and emphysema.We mainly describe the diagnosis,clinical process,and treatment of the patient,including the processes of two plasma transfusion treatments.CONCLUSION This provides a reference for choosing the best timing of convalescent plasma treatment and highlights the effectiveness of the clinical strategy of plasma treatment in the recovery period of patients with COVID-19 pneumonia.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma

Background: Gastrointestinal symptoms are not rare among coronavirus disease 2019(COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients.Case presentation: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration.Conclusion: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

Convalescent plasma therapy in a pregnant COVID-19 patient with a dramatic clinical and imaging response: A case report

BACKGROUND Coronavirus disease 2019(COVID-19)is a novel very contagious infection which was designated a pandemic in all countries of the world in April 2020.Its presentation varies from mild to severe infection,but the majority of infected patients have mild manifestations.Many therapeutic choices have been suggested to treat the infection,but none are fully effective.CASE SUMMARY Herein we present a 26-year-old woman with a twin pregnancy at 36 wk and one day gestation with confirmed COVID-19 who responded dramatically to convalescent plasma therapy(CPT)and Favipiravir.CONCLUSION Although this case report shows the efficacy of CPT in addition to usual medications used for COVID-19,there are many questions that need to be answered regarding dosage,para-clinical efficacy,side effects and combination therapy.

Utility of convalescent plasma for addressing the COVID-19 infection: brief review and case reports

Novel coronavirus,SARS-CoV-2 is responsible for causing a pandemic that has affected individuals worldwide,over 192 million people and about 4.1 million people died so far.The spread is ongoing and the numbers are still increasing.Numerous therapeutic approaches have been explored and developed during this pandemic.Immunotherapy with virus-specific antibodies in convalescent plasma(CP)has shown potential benefits for various pathogenic diseases.In many instances,it is the only available and safe management option for the COVID-19 patients.Here we describe two confirmed cases of COVID-19 from two different geographical areas that were managed with standard treatment modalities initially.Both of the patients were presented with high-grade fever,dry cough,and sore throat.Lab reports showed increased values of D-dimer,serum ferritin,leukocyte count(LC),Lactate dehydrogenase(LDH),and C-reactive protein(CRP).Chest X-ray showed bilateral infiltration(multifocal and bilateral ground-glass opacities and consolidations with peripheral and basal predominance),consistent with the previous reports on COVID-19 infection.The patients received conservative treatment according to the hospital's protocol.The convalescent plasma(from recovered patients)infusion was the last treatment given to both patients.After the convalescent plasma transfusion,both patients showed a reduction of viral load,an increase of anti-SARS-CoV-2 IgG and IgM antibodies,reduction in lung infiltration,with no adverse events.However,further randomized controlled trials are needed to investigate the full scope of safety and efficacy(both short and long-term)of convalescent plasma therapy for COVID-19 and other related infections.

Convalescent plasma as a therapeutic agent for SARS-CoV, MERS-CoV and SARS-CoV-2: A scoping review

Severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2 are three kinds of coronaviruses that are exceptionally pathogenic to humans via zoonotic infections.The outbreaks of SARS-CoV and MERS-CoV,and SARS-CoV-2,to some extent,posed a severe threat to human health,daily activities as well as the economic status of many countries.When faced with these emerging viruses and no accessible vaccines and drugs,convalescent plasma(CP)is required as passive immunotherapy,since CP has the potential to neutralize and eliminate the virus from blood circulation.The sources of CP are individuals who have recovered from the viruses.Currently,CP is administered as emergency use and investigational treatment.Some studies have shown that CP is effective to treat infected individuals with viral pandemics such as influenza A,Ebola virus,SARS-CoV,and MERS-CoV.Moreover,following the deadly outbreak of SARS-CoV-2 in 2019,plenty of non-randomized clinical studies have been done on the effectiveness of CP for the treatment of Coronavirus Disease 2019(COVID-19),and most of these studies have indicated that CP therapy is promising and saved many critically-ill patients.Therefore,CP is a helpful immune therapeutic agent for the immediate response of such pandemics because of its clinical efficacy,immediate availability,cost-effectiveness,ease of production,delivery,and storage.This review aims to summarize the effectiveness of CP in the treatment of these three coronaviruses,i.e.SARS-CoV,MERS-CoV,and SARS-CoV-2.

Effects of Chinese Medicine on Symptoms,Syndrome Evolution,and Lung Inflammation Absorption in COVID-19 Convalescent Patients during 84-Day Follow-Up after Hospital Discharge:A Prospective Cohort and Nested Case-Control Study

Objective:To observe the changes of symptoms,Chinese medicine(CM)syndrome,and lung inflammation absorption during convalescence in patients with coronavirus disease 2019(COVID-19)who had not totally recovered after hospital discharge and whether CM could promote the improvement process.Methods:This study was designed as a prospective cohort and nested case-control study.A total of 96 eligible patients with COVID-19 in convalescence were enrolled from Beijing Youan Hospital and Beijing Huimin Hospital and followed up from the hospital discharged day.Patients were divided into the CM(64 cases)and the control groups(32 cases)based on the treatment with or without CM and followed up at 14,28,56,and 84 days after discharge.In the CM group,patients received the 28-day CM treatment according to two types of CM syndrome.Improvements in clinical symptoms,CM syndrome,and absorption of lung inflammation were observed.Results:All the 96 patients completed the 84-day follow-up from January 21 to March 28,2020.By the 84th day of follow-up,respiratory symptoms were less than 5%.There was no significant difference in the improvement rates of symptoms,including fatigue,sputum,cough,dry throat,thirst,and upset,between the two groups(P>0.05).Totally 82 patients(85.42%)showed complete lung inflammation absorption at the 84-day follow-up.On day 14,the CM group had a significantly higher absorption rate than the control group(P<0.05)and the relative risk of absorption for CM vs.control group was 3.029(95%confidence interval:1.026-8.940).The proportions of CM syndrome types changed with time prolonging:the proportion of the pathogen residue syndrome gradually decreased,and the proportion of both qi and yin deficiency syndrome gradually increased.Conclusions:Patients with COVID-19 in convalescence had symptoms and lung inflammation after hospital discharge and recovered with time prolonging.CM could improve lung inflammation for early recovery.The types of CM syndrome can be transformed with time prolonging.

Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines

The coronavirus disease(COVID-19)pandemic has led to a global struggle to cope with the sheer numbers of infected persons,many of whom require intensive care support or eventually succumb to the illness.The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected.To date,there is no specific anti-COVID-19 treatment.However,the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome,especially in the severe to critically ill.While many of these adjunctive drugs are being investigated in clinical trials,professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use.This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.

COVID-19 Pandemic: Its Origin, Implications and Treatments

This is a succinct and current review of pertinent literature to guide developing serum therapy as an emergent treatment to save human lives at times of natural or genetically engineered viral/bacterial pandemics. The origin of 2019-nCoV and implications of COVID-19 are discussed using direct quotes of published scientific literature to avoid misinterpretation on this very important event that has caused great loss of human lives and international social economy. It is the goal of this review to warn against and to correct international misunderstanding created by deliberate falsification of scientific documentations and events. This misunderstanding may lead to further destruction of life, economy, and political relations. People should not be blind-sighted when making life decisions.

Effectiveness and Controversy of Convalescent Plasma Therapy for Coronavirus Disease 2019 Patients

Since the coronavirus disease 2019(COVID-19)began to spread,it remains pandemic worldwide.The European Medicines Agency’s human medicines committee and Food and Drug Administration have only granted a conditional marketing authorization for remdesivir to treat COVID-19.It is essential to apply other valuable treatments.Convalescent plasma(CP),donated by persons who have recovered from COVID-19,is the cellular component of blood that contains specific antibodies.Therefore,to determine the feasibility of CP for COVID-19,the effectiveness and controversy are discussed in depth here.It is suggested that CP plays a certain role in the treatment of COVID-19.As a treatment,it may have its own indications and contraindications,which need to be further discussed.Meanwhile,it is critical to establish a standard procedure for treatment from CP collection,preservation,transport,to transfusion,and conduct some large sample randomized controlled trials to confirm the transfusion dosage,appropriate time,frequency,and actively prevent adverse outcomes that may occur.

Biopharmaceuticals for prevention of COVID-19:A scoping review

The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.

Patients with Prolonged Positivity of SARS-CoV-2 RNA Benefit from Convalescent Plasma Therapy:A Retrospective Study

Convalescent plasma therapy has been implemented in a few cases of severe coronavirus disease 2019.No report about convalescent plasma therapy in treating patients with prolonged positivity of SARS-CoV-2 RNA has been published.In this study,we conducted a retrospective observational study in 27 patients with prolonged positivity of SARS-CoV-2 RNA,the clinical benefit of convalescent plasma therapy were analyzed.q RT-PCR test of SARS-CoV-2 RNA turned negative(B 7 days)in a part of patients(early negative group,n=15)after therapy,others(late negative group,n=12)turned negative in more than 7 days.Pulmonary imaging improvement was confirmed in 7 patients in early negative group and 8 in late negative group after CP therapy.Viral load decreased in early negative group compared with late negative group at day 3,5,7 after implementing convalescent plasma therapy.Patients in early negative group had a shorter median length of hospital stay.In conclusion,convalescent plasma therapy might help eliminate virus and shorten length of hospital stay in patients with prolonged positivity of SARS-CoV-2 RNA.

Potential benefits,mechanisms,and uncertainties of convalescent plasma therapy for COVID-19

The outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in China led to a public health emergency of international concern,putting all health organizations on high alert in the beginning of 2020.Corona virus disease 2019(COVID-19)is highly infectious and has resulted in thousands of deaths which exceeded that of the SARS coronavirus(SARS-CoV)outbreak back in 2002 and 2003 in China.Besides,the number of diagnosed patients,patients who are suspected to have contracted the disease,and deaths are increasing worldwide.Unfortunately,effective drugs and vaccines to combat SARS-CoV-2 are still lacking.Convalescent plasma,a seemingly successful treatment for COVID-19 patients,proved to be of huge value in terms of saving severely ill patients.This review introduces the reported effects,potential mechanisms,and future uncertainties of convalescent plasma therapy in the treatment of COVID-19 patients,in the hopes that it will provide useful information for relevant physicians and researchers.

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

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 SARSCoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARSCoV-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.

The Progress and Challenges of Convalescent Plasma Therapy for Coronavirus Disease 2019

Middle East respiratory syndrome(MERS),severe acute respiratory syndrome(SARS),and SARS-CoV-2 infection(causing coronavirus disease 2019[COVID-19])are serious diseases.To date,no effective post-exposure prophylaxis,prevention,or therapeutic agents are recommended as effective for these diseases.Convalescent plasma(CP),donated by individuals with established humoral immunity to the virus after recovering from coronavirus infection,has been successfully applied to treat several infectious diseases,including SARS,MERS,and COVID-19.Nonetheless,there are obstacles and challenges to using CP that should be taken into account.In this review,we summarize the evidence derived from clinical attempts to treat COVID-19 with CP,which represents a promising therapy for severe coronavirus infection.Furthermore,we outline the remaining challenges and general issues that should be considered when using CP treatment for therapeutic or prophylactic purposes.

COVID-19 in Liver Transplant Recipients-A Series with Successful Recovery

The severe acute respiratory syndrome corona virus-2 (referred to as SARS-CoV-2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosup-pression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/or convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anti-coagulation, consideration of repurposed drugs (i.e. teico-planin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.

新型冠状病毒肺炎康复者恢复期血浆制备过程对SARS-CoV-2IgG抗体滴度的影响

目的观察新型冠状病毒肺炎康复者恢复期血浆中IgG抗体在亚甲蓝/光化学病毒灭活法和冰冻保存前后滴度的变化。方法随机留取50份2020年2~3月新冠肺炎康复者恢复期血浆的亚甲蓝/光化学灭活前后血浆样辫,冰冻保存,间隔4个月后对其进行SARS-CoV-2 IgG抗体滴度检测。结果亚甲蓝/光化学灭活前后的恢复期血浆IgG抗体滴度差异无统计学意义(P>0.05),冰冻保存4个月后血浆中SARS-CoV-2 IgG抗体滴度变化亦无统计学意义(P>0.05)。结论目前新冠肺炎康复者恢复期血浆的制备程序对血浆中IgG抗体滴度无显著性影响,提示制备流程合理。

武汉808人份新冠康复者血浆的制备特性

目的采集新型冠状病毒肺炎康复者恢复期血浆,进行血液成分制备用于临床新冠危重病患者治疗。方法采集新冠康复出院14 d以上且无发热并符合献血者健康标准的捐献者血浆进行血液成分制备,全封闭无菌分装、亚甲蓝病毒灭活、血浆速冻制备成新冠康复者血浆和病毒灭活新冠康复者血浆供应临床。结果 808人份康复者血浆中A型占39.1%、B型占26.2%、O型占25.4%、AB型占9.3%,检验合格603人份占74.6%,不合格205人份占25.4%(其中血清学IgG抗体<160不合格159人份,其他传染性指标不合格46人份);共制备分装捐献者血浆1 699袋,其中制备新冠康复者血浆133袋(100 mL规格132袋、200 mL规格1袋);制备病毒灭活新冠康复者血浆1 566袋(100 mL规格642袋、150 mL规格4袋、200 mL规格920袋)。结论规范新冠康复者血浆成分制备特性,完善安全有效的制备和防护措施,有效提高临床新冠康复者血浆的安全性和治疗效果。

女性新冠肺炎康复者捐献的恢复期血浆中HLA抗体检测及分析

目的检测分析广州地区女性新冠肺炎(COVID-9)康复者所捐献的恢复期血浆中抗-HLA,以避免输血不良反应的发生。方法参照《新冠肺炎康复者恢复期血浆临床治疗方案(试行第二版)》,借助Luminex技术平台,运用抗-HLA特异性检测试剂盒对检测8位COVID-9女性康复者恢复期血浆中的抗-HLA,再通过GEN-PROBE MATCH IT软件获取捐献者抗-HLA-Ⅰ/Ⅱ的特异性。结果本组女性COVID-19康复者所捐献的血浆中,一次妊娠史共3人,未检出抗-HLA;多次妊娠史共5人, 3人(3/5)检出抗-HLA:其中2人(2/5)为抗-HLA-Ⅰ+Ⅱ阳性,1人(1/5)为抗-HLA-Ⅰ阳性。3人血浆中HLA等位基因主要为A*25∶01(Epitopes为76ESI)、A*29∶02、B*35∶08、DRB1*07∶01(Epitopes为78V2)、DRB1*09∶01(Epitopes为78V2)、DRB1*15∶01(Epitopes为71A)、DPB1*04∶01(Epitopes为35FA)等。结论根据COVID-19康复者恢复期血浆特殊检测要求开展抗-HLA检测,尤其针对有多次妊娠史或输血史的女性康复者,对避免输血相关急性肺损伤(TRALI)的发生十分必要。