Highly Neutralizing COVID-19 Convalescent Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters.

Despite various attempts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with COVID-19 convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly neutralizing COVID-19 convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing activity-determined convalescent plasmas, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in a significant reduction of viral titers in lungs by up to 32-fold compared to the viral titers in hamsters receiving control nonneutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs more than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using microcomputerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19 convalescent plasmas variably contained antibodies against SARS-CoV-2 components, including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent neutralizing activity-confirmed COVID-19 convalescent plasmas would be efficacious in treating patients with COVID-19. IMPORTANCE Convalescent plasmas obtained from patients who recovered from a specific infection have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized controlled clinical trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94 to 95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly neutralizing effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally induced lung lesions. The present data provide a proof of concept that the presence of highly neutralizing antibody in COVID-19 convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

PURPOSE: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique. METHODS: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function. The purified-IgG neutralizing activity of 20 samples from 19 participants and the coagulation factors of 49 samples from 40 participants were evaluated before and after freezing. RESULTS: Purified-IgG maintained its neutralizing activities, with the median 50 % inhibitory concentration (IC50) of 10.11 mg/ml (IQR 6.53-18.19) before freezing and 8.90 m g/ml (IQR 6.92-28.27) after thawing (p = 0.956). On the contrary, fibrinogen and factor Ⅷ decreased significantly after freezing and thawing in our environment. No significant temperature deviation was observed during the storage period. CONCLUSION: Neutralizing IgG activity, which largely contributes to the antiviral activity of convalescent plasma, did not change through our in-house manufacturing, without fastfreezing and storage conditions for more than 200 days. Ordinary freezers without the fast-freezing function are suitable enough to manufacture and store convalescent plasmas. Hospitals or facilities without specified resources could easily collect and store convalescent plasmas in case of upcoming emerging or re-emerging infectious diseases on-demand with appropriate neutralizing antibody levels measurements.

Specific T-cell responses for guiding treatment with convalescent plasma in severe COVID-19 and humoral immunodeficiency: a case report.

BACKGROUND: The immune response to SARS-CoV-2 virus, the cause of COVID-19, is complex. Antibody mediated responses are important for viral clearance but may also drive hyperinflammation in severe COVID-19. We present a case of an individual with a genetic inability to produce antibodies and severe COVID-19, receiving no other specific anti-viral treatment than convalescent COVID-19 plasma, illustrating that hyperinflammation can occur in the absence of a humoral anti-viral response. In addition, the case illustrates that the assessment of SARS-CoV-2 T cell responses can facilitate clinical decision making in patients with COVID-19 and weak or absent humoral immune responses. CASE PRESENTATION: A male with X-linked agammaglobulinemia on regular immunoglobulin replacement therapy, hospitalized for 35 days due to severe COVID-19. Systemic inflammatory parameters were highly elevated. After treatment with convalescent COVID-19 plasma he became afebrile and the fatigue diminished. He was discharged on day 42 and nasopharyngeal SARS-CoV-2 PCR eventually was negative on day 49. Evidence of SARS-CoV-2 specific T cells prior to administration of plasma therapy suggested that antibodies were crucial for viral clearance. Regular assessment showed robust and persistent SARS-CoV-2 specific T-cell responses after recovery suggested that prophylactic administration of convalescent COVID-19 plasma was unnecessary. CONCLUSION: Assessment of SARS-CoV-2T-cell responses can facilitate the clinical management of COVID-19 patients with humoral immunodeficiencies.

Current views on the potentials of convalescent plasma therapy (CPT) as Coronavirus disease 2019 (COVID-19) treatment: A systematic review and meta-analysis based on recent studies and previous respiratory pandemics.

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.

Effect of convalescent plasma therapy on mortality in moderate-to-severely Ill COVID-19 patients.

INTRODUCTION: The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. METHODS: This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. RESULTS: Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. CONCLUSIONS: We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved.

A possible dose-response equation: Viral load after plasma infusion in COVID-19 patients and anti-SARS-CoV-2 antibody titers in convalescent plasma.

BACKGROUND: Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma. METHODS: A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion. RESULTS: Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r = 0.3375, p = 0.04). A possible estimation equation was as follows: Log10 (Reduction in viral load) = 0.18 + 0.001 × (Log2 S-RBD antibody titer × Plasma infusion volume) (r = 0.424, p = 0.009). In a single case, the viral nucleic acid persisted 14 days after the fourth plasma infusion. CONCLUSIONS: This study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.

SARS-CoV-2 IgG Antibody and its Clinical Correlates in Convalescent Plasma Donors: An Indian Experience.

SARS-CoV-2, a novel coronavirus, emerged a year ago in Wuhan, China causing a new pandemic. Convalescent plasma therapy has been applied previously to many infectious diseases and has shown a successful result. This study was planned to assess the Anti-SARS-CoV-2 IgG antibody levels in convalescent COVID-19 patients. In this study, serum samples from 210 persons infected by SARS-CoV-2, treated and discharged from the hospital were collected. Anti-SARS-CoV-2 IgG antibody levels were detected using a chemiluminescence assay. A directory of convalescent plasma donors was created. Anti-SARS-CoV-2 IgG antibody levels vary substantially in the study population with a mean of 51.2 AU/ml. On comparing the serum anti-SARS-CoV-2 IgG antibody levels, a significant difference was observed between the subjects who had cough and those who did not (p = 0.0004). Similar significant findings were found with total protein and globulin levels on comparing the individuals with different antibody status (positive, negative and equivocal). The middle-aged and old age people had high Ab titres compared to younger individuals and the duration of the hospital stay was found to be positively correlated with the anti-SARS-CoV-2 IgG antibody. Cough, age and duration of the hospital stay was found to play a significant role in the development of Anti-SARS-CoV-2 IgG levels. Further, the data suggests that blood groups have a lesser impact on the severity of disease and the development of antibodies. Patients who present with the cough are more likely to develop antibodies.

Effectiveness of convalescent plasma in Indian patients with COVID-19.

BACKGROUND: Convalescent plasma (CP) is being used as a treatment option in hospitalized patients with COVID-19. Till date, there is conflicting evidence on efficacy of CP in reducing COVID-19 related mortality. OBJECTIVE: To evaluate the effect of CP on 28-day mortality reduction in patients with COVID-19. METHODS: We did a multi-centre, retrospective case control observational study from 1st May 2020 to 31st August 2020. A total of 1079 adult patients with moderate and severe COVID-19 requiring oxygen, were reviewed. Of these, 694 patients were admitted to ICU. Out of these, 333 were given CP along with best supportive care and remaining 361 received best supportive care only. RESULTS: In the overall group of 1079 patients, mortality in plasma vs no plasma group was statistically not significant (22.4% vs 18.5%; p = 0.125; OR = 1.27, 95% CI: 0.94--1.72). However, in patients with COVID-19 admitted to ICU, mortality was significantly lower in plasma group (25.5% vs 33.2%; p = 0.026; OR = 0.69, 95%CI: 0.50-0.96). This benefit of reduced mortality was most seen in age group 60 to 74 years (26.7% vs 43.0%; p = 0.004; OR = 0.48, 95% CI: 0.29-0.80), driven mostly by females of this age group (23.1% vs 53.5%; p = 0.013; OR = 0.26, 95% CI: 0.09-0.78). Significant difference in mortality was observed in patients with one comorbidity (22.3% vs 36.5%; p = 0.004; OR = 0.50, 95% CI: 0.31-0.80). Moreover, patients on ventilator had significantly lower mortality in the plasma arm (37.2% vs 49.3%; p = 0.009; OR = 0.61, 95% CI: 0.42-0.89); particularly so for patients on invasive mechanical ventilation (63.9% vs 82.9%; p = 0.014; OR = 0.37, 95% CI: 0.16-0.83). CONCLUSION: The use of CP was associated with reduced mortality in COVID-19 elderly patients admitted in ICU, above 60 years of age, particularly females, those with comorbidities and especially those who required some form of ventilation.

Convalescent plasma is a clutch at straws in COVID-19 management! A systematic review and meta-analysis.

In the absence of definitive therapy for coronavirus disease (COVID-19), convalescent plasma therapy (CPT) may be a critical therapeutic option. This review was conducted to evaluate the impact of CPT in COVID-19 patients based on the publications reported to date. A robust screening of electronic databases was conducted up to 10th July 2020. Randomized controlled trials (RCTs), cohort studies, and case series with a control group evaluating the effectiveness and safety of CPT in patients with COVID-19 are included for the meta-analyses. Our search retrieved seven studies, including two RCTs and five cohort studies, with a total of 5444 patients. In patients with COVID-19, the use of CPT reduces mortality (odd's ratio [OR] 0.44; 95% CI, 0.25-0.77), increases viral clearance (OR, 11.29; 95% CI, 4.9-25.9) and improves clinically (OR, 2.06; 95% CI, 0.8 to 4.9). However, the evidence is of low quality (mortality reduction, and viral clearance), and very low quality (clinical improvement). CPT may be beneficial for reducing mortality, viral shedding and improving clinical conditions in COVID-19 patients. However, further randomized control trials (RCT) are required to substantiate the safety margin, initiation, optimal dosage, titre and duration of CPT.

Antibodies at work in the time of severe acute respiratory syndrome coronavirus 2.

In view of devastating effects of COVID-19 on human life, there is an urgent need for the licened vaccines or therapeutics for the SARS-CoV-2 infection. Age-old passive immunization with protective antibodies to neutralize the virus is one of the strategies for emergency prophylaxis and therapy for coronavirus disease 2019 (COVID-19). In this review, the authors discuss up-to-date advances in immune-based therapy for COVID-19. The use of convalescent plasma therapy as the first line of defense to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been established, with encouraging results. Monoclonal antibodies (mAbs) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein or block the interaction between SARS-CoV-2 RBD and the human angiotensin-converting enzyme 2 receptor have been found to be very promising as a countermeasure for tackling the SARS-CoV-2 infection, and clinical trials are underway. Considering the counterproductive antibody-dependent enhancement of the virus, mAbs therapy that is safe and efficacious, even in people with underlying conditions, will be a significant breakthrough. In addition, emerging immunotherapeutic interventions using nanobodies and cellular immunotherapy are promising avenues for tackling the COVID-19 pandemic. The authors also discuss the implication of mAbs as mediators of cytokine storm syndrome to modify the immune response of COVID-19 patients, thus reducing the fatality rate of COVID-19 infection.

Surrogate test performance for SARS-CoV-2 neutralizing antibodies (nAbs) for convalescent plasma (CCP): How useful could they be?

BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.

Immunological effects of convalescent plasma therapy for coronavirus: a scoping review.

BACKGROUND: Preliminary studies revealed the safety and effectiveness of convalescent plasma (CP) therapy for patients with coronavirus. In this study, we aimed to evaluate and summarize the available evidence on CP therapy, identify the research gap regarding the immunological response to CP therapy and pave the road for future studies. METHODS: This study was conducted according to the Hilary Arksey and Lisa O'Malley framework. To find out the relevant studies, we searched PubMed, Scopus and Embase databases up to 30th May 2021. Data have been extracted according to three categories: (1) patients' characteristics, (2) clinical and immunological responses to CP therapy and (3) pre-infusion screening of the CP samples. RESULTS: A total of 12,553 articles were identified. One hundred fifty-four studies met the inclusion criteria for full-text review. More than half of the included studies (112 studies, (75.6%)) concluded satisfactory outcomes and or safety of CP infusion in patients. Results of studies showed the efficacy of CP therapy in clinical improvement (101 studies), decreasing in the level of inflammatory factors (62 studies), elimination or decreasing in viral load (60 studies), and induction or increase in antibody response (37 studies). Despite these promising results, the results of the 49 studies revealed that CP therapy was ineffective in the survival of patients, clinical improvement, viral infection elimination or decrease in the inflammatory factor levels. Furthermore, the adaptive immune response was evaluated in 3 studies. Information related to the pre-infusion screening for human leukocyte antigen/human neutrophil antigen (HLA/HNA) antibodies was not reported in most of the studies. Our gap analysis revealed that the influence of the CP infusion on the adaptive immune and inflammatory responses in patients with coronavirus needs further investigation. CONCLUSIONS: Based on the results of most included studies, CP infusion was safe and resulted in clinical improvement of patients and decreasing the viral load. The effect of the CP infusion on adaptive immune response and inflammatory cytokines in patients with coronavirus needs further investigation.

Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19.

BACKGROUND: In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. METHODS: The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 µM. The "BX-1 AIDS treatment instrument" was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. RESULTS: BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. CONCLUSION: BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

A matched cohort study of convalescent plasma therapy for COVID-19.

INTRODUCTION: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health crisis. Prior studies demonstrated successful use of convalescent plasma therapy for treatment of other viral illnesses. Our primary objective was to evaluate treatment efficacy of convalescent plasma in patients with COVID-19. MATERIALS AND METHODS: In this retrospective matched cohort study, we enrolled recipients of convalescent plasma collected from donors recovered from laboratory-confirmed SARS-CoV-2 infection under the single patient eIND process. We individually matched 35 cases with 61 controls based on age, gender, supplemental oxygen requirements, and C-reactive protein level at the time of hospital admission. We compared the outcomes of in-hospital mortality and hospital length of stay between the groups. RESULTS: In-hospital mortality was 20% among the cases and 24.6% among the controls (P = .61). A multivariable logistic regression model that included age, gender, duration of symptoms, need for mechanical ventilation, and pharmacologic interventions revealed no significant difference in mortality by study group (P = .71). The median length of stay was significantly greater among convalescent plasma recipients compared with controls, 10 (IQR, 6-17) vs 7 (IQR, 4-11) days, P < .01. The difference was not significant after controlling for covariates (P > .1). CONCLUSIONS: We did not find convalescent plasma reduced in-hospital mortality in our sample, nor did it reduce length of stay. Further investigation is warranted to determine the efficacy of this treatment in patients with COVID-19, particularly early in the disease process.

Different aspects of convalescent plasma therapy for COVID-19 treatment; a critical review.

The novel coronavirus disease (COVID-19) has been declared a pandemic by the World Health Organization (WHO) and is ominously threatening the survival of humankind on the whole planet. With a quick spread of the outbreak from its origin, Wuhan, China, to almost all over the world, it has affected more than seven million people to date, hence it has devastated every part of the infrastructural skeleton of governance. Continuously escalating disease burden and lack of proven therapeutic approaches are mounting challenges to health scientists and ultimately to healthcare providers. Although recent studies have shown benefits in decreasing the severity and duration of the illness and there are more benefits compared to risks, plasma therapy cannot be considered as a standard of care until the ongoing trials are completed and they establish definite evidence on its therapeutic efficacy and safety. Though a beneficial aspect may be there, acquiring donors and adequate availability of plasma is equally challenging, and its associated untoward effects related to biological therapeutic agents. The rational practice of CP therapy guided by risk-benefit judgment from aspects of donor and recipient can be a therapeutic option in such a global health crisis.

Recent updates on immunological, pharmacological, and alternative approaches to combat COVID-19.

The pandemic coronavirus disease 2019 (COVID-19) is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is mainly transmitted via the inhalation route and characterized by fever, coughing and shortness of breath. COVID-19 affects all age groups with no single cure. The drug discovery, manufacturing, and safety studies require extensive time and sources and, therefore, struggled to match the exponential spread of COVID-19. Yet, various repurposed drugs (antivirals, immune-modulators, nucleotide analogues), and convalescent plasma therapy have been authorized for emergency use against COVID-19 by Food and Drug Administration under certain limits and conditions. The discovery of vaccine is the biggest milestone achieved during the current pandemic era. About nine vaccines were developed for human use with varying claims of efficacy. The rapid emergence of mutations in SARS-CoV-2, suspected adverse drug reactions of current therapies in special population groups and limited availability of drugs in developing countries necessitate the development of more efficacious, safe and cheap drugs/vaccines for treatment and prevention of COVID-19. Keeping in view these limitations, the current review provides an update on the efficacy and safety of the repurposed, and natural drugs to treat COVID-19 as well as the vaccines used for its prophylaxis.

Convalescent Plasma Therapy for COVID-19: Lessons from SARS-CoV, MERS-CoV, and H1N1 Infection.

The global widespread mortality after the emergence of SARS-CoV-2 infection in China, has become a critical concern all around the world. Convalescent plasma (CP) therapy is one of the methods elevating the survival rate for COVID-19 infection cases. This technique, as a practicable therapy, was used in previous viral outbreaks including influenza, SARS and MERS. In CP therapy, the blood plasma is collected from persons rehabilitated from that specific infection in order to develop a passive immunity in other patients. Therefore, this review aimed to point out the role of CP therapy in aforementioned viral infections and illustrate different factors influencing the efficacy of CP therapy.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Treatment with convalescent plasma for COVID-19 patients in Wuhan, China.

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak of coronavirus disease 2019 (COVID-19) are causing public health emergencies. A handful pieces of literature have summarized its clinical and radiologic features, whereas therapies for COVID-19 are rather limited. To evaluate the efficacy of convalescent plasma therapy in COVID-19 patients, we did this timely descriptive study. Six laboratory-confirmed COVID-19 patients were enrolled and received the transfusion of ABO-compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground-glass opacities and consolidation in patients #1, #2, #3, #4, and #6. In patients #1 and #5 who presented with SARS-CoV-2 in throat swab, convalescent plasma therapy elicited an elimination of the virus. Serologic analysis indicated an immediate increase in anti-SARS-CoV-2 antibody titers in patients #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID-19. This intervention has a special significance for eliminating SARS-CoV-2 and is believed to be a promising state-of-the-art therapy during COVID-19 pandemic crisis.