Convalescent plasma has the potential to heal those affected by Covid-19
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Introduction
At the time of this writing on April 8, the global outbreak of the new Coronavirus disease (Covid-19) had resulted in over 1 353 361 cases confirmed and 79 235 deaths globally; in the African region there were 7 647 confirmed cases and 326 deaths. There is no treatment, outside of supportive care, that has proven effective against Covid-19. Specific medicines for the treatment of this disease will have to go through rigorous development in clinical trials and regulatory processes to ensure their safety and effectiveness before they can be available for routine use.
One potential treatment under investigation for Covid-19 is the transfusion of convalescent plasma collected from former patients who have recovered from Covid-19 into those who are still affected. This experimental therapy has a promising theoretical rationale and the advantage that it can be made available rapidly through local production in blood establishments. Importantly, the use of convalescent plasma or serum was suggested by the World Health Organization (WHO) Blood Regulators Network, when vaccines and antiviral drugs were unavailable for an emerging virus (Organization, 2020b) and has been addressed in a recent interim guideline. Consistent with the advice of WHO, the African Blood Regulators Forum(ABRF) also supports the view to utilise Covid-19 convalescent plasma as an investigational therapy that may save lives in the African context. For these reasons, Ministries of Health need to give immediate and serious consideration to promoting the use of Covid-19 convalescent plasma in appropriately conducted studies.
Scientific basis for passive immunotherapy
Convalescent plasma is the straw-yellow liquid part of blood that may be rich in antibodies against an infectious disease, which can be collected from a blood donor who has recovered from that infectious disease. Treatment with convalescent plasma is a form of serum therapy (passive antibody therapy) that was first discovered in the 1890s by Emil von Behring as a treatment for diphtheria. Until the advent of antibiotics in the 1940s, serum therapies were the only known means of treatment for many infectious diseases, including viral diseases. Passive antibody therapy involves the administration of antibodies from an infectious disease agent to a susceptible individual to prevent or treat an infectious disease due to that infectious agent (Casadevall & Pirofski, 2020). Passive antibody administration can provide immediate, though transient, protective immunity to susceptible persons including highly immunocompromised patients. Convalescent plasma may contain neutralizing antibodies relevant to a virus that can mediate protection through neutralization of an infectious inoculum. In the setting of disease, the anti-viral effect of treatment with specific antibodies may provide a clinical benefit depending on the nature of the antibodies, the administered dose and the condition of the patient.
Promising historical experience
It is possible that convalescent plasma collected from recovered Covid-19 patients contains antibodies to SARS-CoV-2 (the virus that causes Covid-19) that might be effective against the infection. Convalescent plasma or purified immunoglobulins appeared to improve the survival rate of patients in previous outbreaks of other respiratory infections including the 2003 SARS-CoV-1 epidemic, the 2009 – 2010 influenza A H1N1 virus pandemic and the 2012 MERS-CoV epidemic. Moreover, several studies revealed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. In previous reports, most of the patients received the convalescent plasma by single transfusion.
In a study involving patients with pandemic influenza A(H1N1) 2009 virus infection, treatment of severe infection with convalescent plasma (n = 20 patients) was associated with reduced respiratory tract viral load, serum cytokine response and mortality. In another study involving 80 patients with SARS according to Shen, Wang, Zhao, Yang, Li, Yuan, Wang, Li, Yang and Xing (2020), administration of convalescent plasma was associated with a higher rate of hospital discharge at day 22 from symptom onset compared with patients who did not receive convalescent plasma. Accordingly, these findings support the hypothesis that convalescent plasma transfusion could be beneficial in patients infected with SARS-CoV-2 (Shen et al., 2020). Therefore, it might be worthwhile to test the safety and efficacy of convalescent plasma transfusion in SARS-CoV-2-infected patients (Chen, Xiong, Bao & Shi, 2020). A recent report from China where Covid-19 convalescent plasma was used to treat five critically ill patients indicated that it was effective, as the patients recovered well.
Position of ABRF
Addressing the current SARS-CoV-2 virus epidemic and the associated high mortality is an urgent health priority for African countries. With the background knowledge that already exists on the concept of passive immunisation, the general possibility exists that application of convalescent plasma might be effective in Covid-19 treatment. This treatment option can be made available immediately as long as there are Covid-19 survivors capable of donating their plasma and an adequately developed blood service. For this reason, it is prudent for the African countries through the Ministries of Health to urgently consider the use of convalescent plasma as a potential treatment option in response to this pandemic.
African countries need to co-ordinate and organise a program to collect convalescent plasma from Covid-19 survivors. This convalescent plasma could provide a potentially valuable intervention in the interim, while data on effectiveness and safety of its use is obtained through orderly scientific studies. The decision to pursue this option needs to be swift, to avoid potentially preventable loss of many African lives. It is estimated that approximately 80% of people infected by Covid-19 develop only mild or inapparent symptoms and recover fully without the need for special medical attention. As more individuals contract Covid-19 and recover, the number of potential donors will continue to increase.
Governments in African countries will need to mobilise within their health systems and infrastructure for the best outcomes for patients. The National Blood Services, National Regulatory Authorities, and Ethics Committees among other national institutions will need to coordinate a Covid-19 convalescent plasma program with the local treatment facilities. Clinical use of convalescent plasma for this novel viral infection should be used as an investigational treatment option under controlled study conditions following national regulations. Clinicians should spearhead the program and should develop a study protocol that meets ethical requirements from regulatory authority and local Institutional Review Boards as well as clinical trial requirements. A protocol for treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015 (Shen, Wang, Zhao, Yang, Li, Yuan, Wang, Li, Yang & Xing, 2020). This approach with other viral infections such as SARS-CoV, H5N1 avian influenza, and H1N1 influenza also suggested that transfusion of convalescent plasma was effective (i.e. well-monitored observational studies and/or randomized trials.). Various protocols for use of Covid-19 convalescent plasma already exist in several countries and regions. Under appropriate protocols, the NBS can collect convalescent plasma from patients recovered from Covid-19 that contains SARS-CoV-2 specific antibodies at their facilities.
Collection of convalescent plasma in the country should be relatively easy, as the process is similar to normal blood collections, except that in this case special donors are required. The NBS, which already has expertise in blood donor mobilisation and blood collection should be responsible for the collection and processing of convalescent plasma. Existing operational policies, standards and procedures governing blood transfusion within countries must be observed to ensure the quality and safety. Only voluntary Covid-19 survivors meeting the existing national criteria for blood donation should be allowed to donate convalescent plasma. Public awareness campaigns can be conducted to make correct information readily available in the country.
Use of convalescent plasma for treatment and prevention of Covid-19 infection is a readily available option available for the African Countries to manage this pandemic. This product can be produced and used locally which makes it the ideal measure in the interim before other treatment options are available. For an effective program, African countries and their governments must lead from the front and bring all the relevant stakeholders to the table to protect Africans. — Khamusi Mutoti – ABRF Chairperson and Linda Mudyewenyama – ABRF Rapporteur on behalf of ABRF
Position of the African Blood Regulators Forum (ABRF) on Use of Convalescent Plasma in Africa as a Potential Therapy in Covid-19. @Nepad_Agency