|Year : 2021 | Volume
| Issue : 1 | Page : 64-85
Use of convalescent plasma for COVID-19 in India: A review & practical guidelines
Niranjan Shiwaji Khaire1, Nishant Jindal1, Lakshmi Narayana Yaddanapudi2, Suchet Sachdev3, Rekha Hans3, Naresh Sachdeva4, Mini P Singh5, Anup Agarwal6, Aparna Mukherjee6, Gunjan Kumar6, Ratti Ram Sharma3, Vikas Suri1, Goverdhan Dutt Puri2, Pankaj Malhotra1
1 Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
2 Department of Anaesthesia & Intensive Care, Postgraduate Institute of Medical Education & Research, Chandigarh, India
3 Department of Transfusion Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
4 Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
5 Department of Virology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
6 Clinical Trial & Health System Research Unit, Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, New Delhi, India
|Date of Submission||19-Jul-2020|
|Date of Web Publication||26-Mar-2021|
Dr. Pankaj Malhotra
Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.
Keywords: Antibody-dependent enhancement - anti-SARS-CoV-2 antibodies - convalescent plasma - COVID-19 - donor selection - neutralizing antibodies - passive immunization
|How to cite this article:|
Khaire NS, Jindal N, Yaddanapudi LN, Sachdev S, Hans R, Sachdeva N, Singh MP, Agarwal A, Mukherjee A, Kumar G, Sharma RR, Suri V, Puri GD, Malhotra P. Use of convalescent plasma for COVID-19 in India: A review & practical guidelines. Indian J Med Res 2021;153:64-85
|How to cite this URL:|
Khaire NS, Jindal N, Yaddanapudi LN, Sachdev S, Hans R, Sachdeva N, Singh MP, Agarwal A, Mukherjee A, Kumar G, Sharma RR, Suri V, Puri GD, Malhotra P. Use of convalescent plasma for COVID-19 in India: A review & practical guidelines. Indian J Med Res [serial online] 2021 [cited 2021 Apr 22];153:64-85. Available from: https://www.ijmr.org.in/text.asp?2021/153/1/64/308620
| COVID-19 in India|| |
The cases of COVID-19 in India, the pandemic caused by SARS-CoV-2, has reached to 10,582,647 and total deaths above 152,000 on January 19, 2021. There is currently no proven specific therapy, and multiple novel and repurposed molecules are being used on an experimental basis. The lack of effective therapeutic options has been a major hurdle in our pandemic mitigation measures.
| Convalescent plasma (CP), an overview|| |
Convalescent plasma (CP) is a mode of passive immunization wherein preformed antibodies against an infectious agent are infused into a susceptible host with the aim of either preventing or treating the infection [Figure 1]. CP was widely used in the past to treat several bacterial (diphtheria, tetanus, pneumococcal pneumonia and meningococcemia) and viral infections (rabies, poliomyelitis and measles) in the pre-antibiotic era,,. Safer and more standardized modalities such as hyperimmune globulins and monoclonal antibodies are currently available against diseases caused by agents such as Clostridium tetani, hepatitis A and B, rabies and respiratory syncytial virus [Figure 2]. CP still retains an important place in the management of infections caused by novel pathogens because of the rapidity and ease with which it can be put to clinical use [Table 1]. Hence, it has been widely used during almost all recent epidemics, including H1N1 influenza,, SARS,, Middle East respiratory syndrome (MERS), and Ebola,. Most of the literature from these epidemics is in the form of case reports or series. There are very few randomized control trials (RCTs), or systematic reviews and meta-analyses,. Past experience unequivocally attests to CP's safety with very few adverse events reported,. Pooled analyses suggest the benefit of CP use in diseases such as H1N1, SARS and Argentine haemorrhagic fever, especially when used early in the illness,. Data from across the globe regarding various aspects of CP use are accumulating at a fast pace. The current review aims to summarize the available evidence in COVID-19 disease and provide the recommendations for setting up CP protocols in clinical and research settings.
|Figure 1: Overview of convalescent plasma (CP) therapy. The Figure shows the process of CP donation and its use in a patient with COVID-19. CP contains over a thousand types of proteins. Apart from the antibodies against SARS-CoV-2, various other proteins may contribute to the beneficial effects of CP administration, including anti-inflammatory cytokines, complement and clotting factors.|
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|Figure 2: Post-donation modifications of convalescent plasma (CP). The Figure shows the possible post-donation modifications to CP to create safer, more potent, standardized passive immunization products such as hyperimmune globulins and monoclonal antibodies against SARS-CoV-2.|
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|Table 1: Suitability of convalescent plasma (CP) use during outbreaks by novel pathogens|
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| Immunological aspects of convalescent plasma therapy in COVID-19|| |
CP therapy involves collecting plasma from an individual who has recently recovered from infection and infusing it into an at-risk individual, [Figure 1]. Such plasma contains several humoral factors capable of providing immunity, but the most important one is believed to be the polyclonal antibodies against the target agent. CP confers immune-protection by numerous mechanisms [Figure 3]. Direct viral neutralization by neutralizing antibodies (NAbs) and the immunomodulatory actions that limit host damage are important mechanisms in COVID-19.
|Figure 3: Mechanisms of action of convalescent plasma (CP). The Figure depicts the multiple possible mechanisms of action of CP. Of note, there are multiple non-antibody-based as well as non-viral neutralization-based mechanisms of action. Hence, CP with low or absent anti-SARS-CoV-2 antibodies can theoretically provide beneficial effect when administered to COVID-19 patients. ADCC, antibody dependent cellular cytotoxicity.|
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Immunological studies have demonstrated a diverse antibody repertoire in the serum of recently recovered patients. Antibodies directed against the receptor-binding domain of the viral spike protein (S-RBD) bind them, limit cell entry, and inhibit the virus amplification. Laboratory studies have shown potent neutralizing activity by such antibodies repertoire against the live virus,,,,. The majority of patients achieve seroconversion within two weeks of symptom onset,,, [Figure 4]. While data regarding the long-term duration of this humoral response in COVID-19 are still evolving, studies conducted during the SARS epidemic have shown that this antibody response is short-lasting, with peak levels at around 3-4 months followed by gradual waning over the next two years.
|Figure 4: Current understanding of the relevant immunological concepts in COVID-19. The Figure explains the current concepts in the humoral immune response of COVID-19. (i) IgM antibody production starts at around 4-7 days, peaks by approximate week three and wanes gradually by 3-4 months from symptom onset,,. (ii) IgG antibody production starts at around 10-14 days. The disappearance of IgG response is not exactly known; however, based on data during the earlier SARS epidemic, it is expected to be short-lasting and be undetectable in most individuals by 24-36 months. (iii) Period of infectivity peaks a couple of days before symptom onset.|
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| Measurement of antiviral activity of convalescent plasma: Neutralizing antibody titers|| |
The neutralizing activity of CP directly quantifies the plasma's protective activity and has been used as a gold standard for the quantification of its efficacy. These are functional assays that involve incubating serial dilutions of the plasma with a standard dose of the live virus and inoculation of this mixture in a culture medium. The dilution of the plasma that prevents the culture of the virus or its cytopathic effect is defined as the neutralizing titre of the plasma. However, these assays are not available on a large scale for CP therapy because of accessibility and standardization problems.
The use of commercially available serological assays as alternatives to neutralizing assays is an attractive option. A few recent publications have demonstrated a good correlation of several such serological titres, especially assays targeting the S-RBD domain and neutralizing assays,,,,. The New York Blood Centre (NYBC) found that two commercial assays (by Abbott and ORTHOS) showed a good correlation with NAb titres in a study of serum from 370 CP donors. The ConCOVID group investigators from the Netherlands found a good correlation of a commercially available ELISA with neutralization assays,. The assay manufactured by EuroImmun AG has also been shown to correlate with neutralization assays and used in a RCT from Spain. Another issue in the antibody titre measurement of CP is the wide variability in the methodology and cut-offs used in the literature [Table 2]. Ideally, these parameters need to be standardized and validated in clinical trials before clinical use.
|Table 2: Challenges in the development of assays for antibody titre quantification for convalescent plasma (CP) therapy|
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| Ideal donor|| |
A potential CP donor for COVID-19 is a healthy adult who has recently recovered from COVID-19 infection and remained asymptomatic for a minimum of 14 days. This period is based on the estimates of antibody kinetics and period of infectivity [Figure 4]. Documented nasopharyngeal swab PCR negativity before CP donation is no longer mandatory in most CP protocols across the globe. Based on the available antibody kinetics data, the ideal window for donation is 3-4 months after symptom onset.
There is a wide variability in the titres of anti-SARS-CoV-2 antibodies within donors. Initial data from China showed that a high proportion of donors (39/40) possessed NAb titres >1:160. However, recent reports have shown more variations. In the NYBC report, 55 per cent of the screened 370 CP donors did not have high titre antibodies, while 10 per cent had very high levels. The ConCOVID group reported similar findings in a cohort of 115 plasma donors, with 43 per cent screened donors having neutralizing titres >1:320 and 10 per cent with titres >1:1280. In other studies, the proportion of donors found lacking in high titre antibodies ranged from 25 to 50 per cent,,, with about 10-20 per cent having very high antibody levels of more than 20 times the cut-off limits, the so-called super-donor phenotype. Older age, male gender and clinical features such as moderate-to-severe disease, high C-reactive protein (CRP) and lymphocytopaenia, have been found to be associated with higher NAb titres. Notably, asymptomatic individuals have been found to mount a very transient and low titre antibody response. These clinical and demographic factors may help guide the selection of suitable donors.
Ideally, donor selection should be based on their NAb titres, but such an approach is currently not feasible in India [Table 2]. Due to the unavailability of such assays, most clinical and trial protocols are proceeding with CP therapy without quantification of antibody titres. Of note, the compassionate use programmes in the USA and Israel followed this approach and determined antibody titres of the infused plasma units post hoc, and their findings have been recently published,. The Indian Council of Medial Research (ICMR)-sponsored PLACID trial also followed this strategy. The antibody titres in this study were found to be low, with a median neutralization titre of 1:40 [interquartile range (IQR) 1:30-1:80]. These findings have highlighted the hazards of proceeding with CP therapy without appropriate antibody quantification in real time. For now, it seems to be a reasonable strategy to screen potential CP donors for the presence of anti-SARS-CoV-2 antibodies using commercially available serological tests to exclude donors with low anti-SARS-CoV-2 antibodies.
| Process of plasma donation|| |
A prospective donor should fulfil the standard donor screening criteria, as per the Drugs and Cosmetics Rules, 1945, and the COVID-19 advisory from National Blood Transfusion Council (NBTC). Plasma donation is a voluntary exercise and requires informed consent. Although whole blood can be used in resource-limited settings, plasmapheresis remains the preferred method of CP donation because of the larger collection volume of plasma, the feasibility of repeated collections and the minimal impact on the donor's haemoglobin. Up to 15 per cent of total blood volume (400-800 ml per session) can be safely donated in a single sitting,,,. Recommendations allow for serial plasma donations by a single donor with a minimum gap of seven days between consecutive plasmapheresis sessions,.
Donated plasma is frozen at less than −30°C (preferably −40 to −80°C) within 8-24 h of collection and can be stored for up to 12 months. Pathogen inactivation by techniques such as photochemical inactivation or solvent detergent treatment and pooling from multiple donors are other post-donation processing options to improve the safety and quality [Figure 2].
| Clinical use of convalescent plasma|| |
Despite the widespread use and publicity of CP, it remains an experimental therapy. Conclusive proof of its efficacy and the parameters of its effective use remain to be firmly established. In such a situation, it is advisable to use CP only under a research protocol after discussing the experimental nature and potential risks of CP use with the recipient.
The use of CP can be envisioned primarily in four clinical settings. The factors related to the dosing of CP in different settings are summarized in [Table 3] and [Table 4]. A cardinal principle is that earlier use in the course of illness is expected to be more beneficial,. Early in the course of the disease, the viral burden is less, and the infection is not yet firmly established. The hypothesized mechanism of action of CP is by prevention or delay in the establishment of infection long enough to allow for the host immune response to clear the infection. In the latter stages of illness, the hyper-inflammatory state is the major driver of morbidity. The ongoing tissue damage maintains the inflammatory state as a vicious cycle, and control of viral replication may have a minimal effect on disease course. As a corollary, CP may be expected to be an effective modality for post-exposure prophylaxis. [Table 4] shows the suggested dosing for use of CP in different clinical settings.
|Table 4: Factors to be considered to determine the accurate dose of convalescent plasma (CP)|
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Accumulating evidence suggests that any potential benefit of CP use may be found in mild and moderate illness rather than the critically ill,. Studies during the SARS epidemic showed CP to be more useful in symptomatic patients who were seronegative and PCR positive. Results from the RCT from the Netherlands suggest the need to choose such seronegative COVID-19 patients early in the course of illness. However, the shortages of high antibody titre donors preclude the use in prophylactic or mild illness settings on a large scale. Thus, in the current scenario, the potential use of CP may be prioritized in the following settings: (i) Post-exposure prophylaxis for healthcare workers; (ii) Post-exposure prophylaxis of individuals with comorbidities at higher risk of severe illness; and (iii) Treatment of symptomatic individuals with moderate disease, especially in the first week of illness.
| Risks of convalescent plasma use|| |
Despite the use of guideline-based screening strategies, CP carries a non-zero risk of transfusion-associated infections. Other complications include allergic reactions, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO). COVID-19 patients with their compromised respiratory reserve are especially vulnerable to TRALI/TACO, which may be difficult to distinguish from the progression of COVID-19. In the periodically published safety analyses from the Expanded Access Program (EAP) in the USA where the safety data of the first 5000 and later 20,000 patients have been reported, the incidence of these reactions was very low (<1%), and only two serious adverse events could be conclusively attributed to plasma therapy. Another theoretical concern is the antibody-mediated enhancement of infectivity, a phenomenon described with several viral infections such as dengue,. It is believed to occur when an individual harbours pre-existing antibodies against a closely related strain of the virus (such as the SARS-CoV-1, MERS or other coronaviruses). It is hypothesized that these pre-existing antibodies are sub-neutralizing in nature and mask the viral epitopes from immune recognition, thus facilitating intracellular entry and survival, leading to a paradoxical worsening of the illness. There is no evidence available to suggest the role of antibody-mediated enhancement in COVID-19.
| Worldwide use of convalescent plasma in COVID-19|| |
The earliest reports of CP use came from China. These and other initial reports have been summarized in [Table 5]. By early March, CP therapy was adopted in the USA, Italy, Israel, Spain and several other countries on compassionate grounds in severely ill patients or as part of clinical trials. Several large single-arm studies from these centres [Table 6] provided a proof of concept and established the feasibility and safety of CP in COVID-19. These have reinforced the general theme that earlier administration is associated with better outcomes. The limitations of these studies included small sample sizes, absent or non-randomized control arms, simultaneous use of multiple experimental therapies and a non-uniform study design and donor selection criteria. Most of these studies were in severe and critically ill patients.
|Table 5: Initial case reports and case series in the use of convalescent plasma (CP) in COVID-19|
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The largest experience of systematic use of CP in COVID-19 comes from the USA. Apart from the on-going clinical trials and the compassionate use under the Emergency Investigational New Drug (eIND) license from FDA, CP has been made accessible to patients and clinicians under the EAP of the USFDA. Under this programme, more than 80,000 units of CP were infused, and the safety analysis of this programme was mentioned earlier,. The group recently published their post hoc analysis after determining the NAb titres in 35,322 patients ([Table 6], row 10). The two main findings were that infusion of CP within three days of diagnosis compared to later showed benefit in seven-day mortality (8.7 vs. 11.9%, P<0.001) and that there was a dose-response curve for mortality with respect to infused antibody titres. The patients who received CP units with low, medium and high antibody titres had a mortality of 13.7, 11.6, and 8.9 per cent. The antibody titres were not known at the time of the administration of CP. Hence, the arm with low-titre CP can be considered an internally blinded control arm. Similarly, Israel's compassionate CP use programme has also shown a dose-response curve between titres and mortality in their post hoc antibody titre analysis involving 49 patients. Several other single-arm studies have been published, a few with matched control arm with claims of CP use efficacy [Table 5] and [Table 6].
This evidence, although compelling, has not been replicated in the initial RCTs on CP. The first RCT on CP therapy in COVID-19 was an open-label RCT from seven centres in Wuhan ([Table 6], row 5). It was terminated early due to slow recruitment, with only 103 of the target 200 individuals enrolled. This trial employed high titre CP units and showed a higher rate of clinical improvement in severely ill patients but not in the critically ill. There was earlier symptom resolution and viral clearance in the CP arm. The limitations were the lost statistical power due to early termination, lower dosing than other studies and the long median time of >30 days from symptom onset to plasma infusion.
A multicentre open-label RCT from 14 centres from the Netherlands randomized 86 of the planned 462 patients and gave CP to 43 ([Table 6], row 9). CP with median neutralizing titres 1:640 was infused. The cohort was predominantly with mild illness and admitted early in the course of disease with a median time from symptom onset of 10 days. While there was a trend towards mortality benefit in the CP arm (26 vs. 14%), there was no significant outcome difference between the two arms. Moreover, 80 per cent of the enrolled patients had anti-SARS-CoV-2 antibodies in their serum at baseline with titres comparable to those of the 115 convalescent donors. The titres of the infused CP units were higher than these baseline recipient titres, and more than a four-fold rise of titres within a week could be demonstrated amongst CP recipients. The RCT was halted for revision of design since the investigators reasoned that administering CP to already seropositive patients would confer no additional benefit.
Another RCT from Spain was halted prematurely due to a fall in recruitment ([Table 6], row 13). The data on 81 patients enrolled who received high titre CP with median titres of 1:292 (IQR 168-882) showed a mortality benefit at day 14 compared to the control arm; however, the number of events was very low.
Most recently, the ICMR-sponsored PLACID trial also published its findings ([Table 6], row 15). This open-label RCT could recruit its target, unlike the earlier RCTs and randomized 462 patients. There was no difference in mortality or progression to severe disease between the plasma and the control arm. A high proportion of participants had anti-SARS-CoV-2 antibodies at the time of enrolment, and their antibody titres were higher than those of CP donors. This trial replicated the real-world use of CP, wherein the antibody titres of CP were not known a priori. However, the median antibody titres in the infused CP units were significantly lower than the EAP or the Israel compassionate use data,. The median NAb titres of infused plasma in this study were 1:40. Whether this reflects the heterogeneity of antibody responses in the Indian population versus the Western population remains to be seen. This experience established the need to have adequate antibody testing for CP done before its use in any trial setting.
Another important RCT on CP use was published in November 2020 by the PlasmAr group from Argentina73 ([Table 6], row 17). They enrolled 333 patients of mild to moderately severe COVID acute respiratory distress syndrome (ARDS). However, no mortality or difference in clinical outcome could be demonstrated between the two groups. The median titre of neutralizing antibody used in the study was 1:300, although the median time of administration was eight days, a relatively later time period in the course of disease. Only 39 patients were enrolled within 72 h of symptoms, a number too small to test the hypothesis of administration of CP within first three days of illness. Conversely another double blind RCT from Argentina by the INFANT-COVID-19 group conducted in elderly patients with mild COVID disease who were given high titre CP. The results showed decreased progression to severe disease in patients who received CP and favoured the use of CP in this group ([Table 6], row 16). In particular, all the recipients of CP received the infusion within 72 h of diagnosis. Another smaller RCT conducted in a single centre in Kolkata in 80 patients demonstrated a significant decrease in the hyperinflammatory cytokine response in patients with mild to moderate COVID ARDS ([Table 6], row 18). Although there was no demonstrable clinical benefit in terms of survival, duration of hypoxia or duration of hospital stay, there was some benefit noted in the subgroup of patients aged below 67 years.
CP therapy has been granted the Emergency Use Authorization in the USA on August 23, 2020. The high titre CP units in this authorization have been defined as having antibody titre with signal/cut-off ratio >12.
| Is there a need for further randomized control trial for convalescent plasma use in COVID-19?|| |
Until now, in the RCTs the infusion of high-quality CP in the requisite number of patients could not be done either due to poor recruitment or poor titres of antibodies. The two RCTs from Argentina, which could infuse high antibody titre plasma to the target population showed contrasting results. While there was no benefit in infusion of plasma in moderate to severely ill patients in the PlasmAr study, there was benefit when it was given in mildly ill elderly pateints within three days of diagnosis in INFANT-COVID-19 group. While more than 100,000 units of CP has been used worldwide, there is still not unequivocal evidence for or against CP use. Therefore, there remains a need for further scientifically designed RCTs to answer these questions. There are hypotheses to suggest that even seropositive patients may derive the benefit of CP use by augmentation of natural antibody response, immunomodulatory actions and avoidance of cytokine storm. However, these aspects can be explored once the efficacy of CP's use has been established.
At present, there are over 100 registered trials worldwide investigating CP in COVID-19,,. Apart from the recently published PLACID trial from India49 including a large-scale trial called the PLATINA, which is an open-label RCT of CP use in severe COVID-19 illness, recruiting in 21 centres across Maharashtra (CTRI/2020/06/026123).
| Convalescent plasma use in India|| |
If proven beneficial in COVID-19, CP may be a promising treatment option for India. However, efforts will have to be made to make antibody testing available before any large-scale CP use programme in the country, after learning from the PLACID trial experience. Setting up a centralized antibody titre determination system under the aegis of a competent authority may help overcome such problems. Another operational requirement would be to ensure that patients receive CP units as soon as possible, ideally targeting infusions within three days of diagnosis. The scarcity of donors is another major problem. Creating a CP stockpile large enough to treat patients, provide prophylaxis for healthcare workers and provide enough raw material for producing purified products in the future requires a major public health initiative. Motivating eligible donors for multiple sessions of plasmapheresis is necessary to overcome these shortages.
Voluntary blood donation has always been a challenge in India, and these problems are compounded further for CP. Multiple barriers for CP donation exist among donors. The most common reasons for reluctance to donate include fear of visiting a healthcare facility during an epidemic, fear of waning of immunity and risk of reinfection due to CP donation. The imposition of lockdowns and curfews also leads to restricted mobility of donors to visit CP donation sites.
The Drug Controller General of India has approved the drug to be administered only under a trial protocol. The Ministry of Health and Family Welfare (MoHFW) guidelines for the treatment of COVID-19 lists CP as an off-label experimental therapy option. These guidelines recommend using CP after the measurement of antibody titres by neutralization assays or anti-S-RBD IgG ELISA, which may not be possible in most centres of the country. For the design of clinical and research protocols guidelines issued by global regulatory bodies such as WHO, International Society of Blood Transfusion (ISBT),, USFDA and European Commission may be useful.
| Social and ethical implications of convalescent plasma in India|| |
CP therapy for COVID-19 presents with its own unique social and ethical challenges. Although unproven in efficacy, there is a demand for CP therapy, especially in critically ill hospitalized patients. Avoidance of monetary or other coercion is necessary to avoid the exploitation of CP donors. Plasma donation appeals should be only of pro-social altruistic nature and should be completely voluntary. It is necessary to ensure that available plasma is rationed in an unbiased and evidence-based manner. Documentation of outcomes should be mandatory. The formation of a nationwide registry of CP use may go a long way to address these issues.
| Conclusions|| |
CP may be a promising and safe treatment option for COVID-19 and is feasible in the Indian setting. Its efficacy in this setting remains to be unequivocally established. Further research on donor selection, antibody cut-offs, precise indications of use and dosing is required before more widespread CP use becomes possible. Emerging evidence points out the necessity of measuring antibody titres in infused plasma units and selecting high titre units for infusion. The recommendations regarding various aspects of CP therapy are summarized in [Table 7]. The development of more potent modalities such as hyper-immune globulins would be the next step in enhancing passive immune transfer-based therapeutics for COVID-19 [Table 8].
|Table 7: Recommendations for various aspects of convalescent plasma (CP) therapy|
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Acknowledgment: The graphics for the article were designed by huephoria (http://huephoria.in/).
Financial support & sponsorship: None.
Conflicts of Interest: None.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]