The gift of immune ammunition: convalescent plasma for COVID-19

Eliza Shapiro writes in New York Times how her dreadful days of COVID-19 infection and suffering concluded on a positive note when she learned she can gift her plasma to other patients who were still fighting this battle. While the scientific community is still putting the nuts and bolts together to get a perspective on best approach to combat COVID-19 pandemic, convalescent plasma therapy appears as a major victory so far against this unfamiliar intruder who has created havoc around the globe. As the best and advanced technologies are being put forth to make a breakthrough, plasma therapy is an “old is gold” way to scare the virus. One of the practices in which infections are controlled rely on “passive immunity” that is passed on when an individual is injected with antibodies from an external source as they still haven’t produced their own. Antibodies are one of the key players in the immune response we mount to get rid of infections including acute viral diseases such as COVID-19. 

When an invader like virus enters our body, B cells fire bullets called antibodies to neutralize these pathogens. Initially there are several versions of the “bullets” that target different regions of pathogen that has been already been chopped down to pieces. Antibodies that are more efficacious auto stimulate their cells to produce copious amounts of copies and they persist longer, while the other versions fade away. This fine tuning of the righteous bullet is the reason for lag period in infection and immune response our body mounts. Antibodies also vary in their type, specificity and volume over the course of infection and they even exist post infection. Does that imply they can save us by fighting re-infection as there is no delay in stimulation, selection and production? Of course, it does mean that and during re infections they are even more efficacious and can prevent us from actually getting reinfection. 

Initially while fighting the infections, antibodies are usually IgM but the residual antibodies after infection persist as IgG and form the basis of passive immunity and convalescent plasma therapy. It’s specifically important in the window period when patients with an active disease have lag time in productions of antibodies and few others may also have impaired response if their antibodies are not as effective as mounted by others. How potent is this plasma therapy in fighting COVID depends on the composition of plasma? In this latest paper from Robbiani et al, the authors have explored what promise lies in this immune ammunition gift. 

While previously in few case studies, the plasma therapy has shown positive results indicated by recovery of the patients, in this study, the authors have explored the potency of antibody responses in COVID-19 convalescent plasma. They recruited participants who were either diagnosed with SARS-CoV-2 infection by RT-PCR or were close contacts of individuals diagnosed with infection. RT-PCR detects the virus by amplifying its genetic material and offers more sensitivity compared to serum testing through ELISA. The patients recruited in the study were free of symptoms like fever, fatigue, cough and myalgia for 14 days at the time of sample collection ensuring that they have recovered from infection. Plasma samples were tested for binding to two predominant proteins of SARS-COV-2 including receptor binding domain (RBD) and trimeric spike proteins by a validated ELISA using IgG, IgM secondary antibodies for detection. 78% of the patients had anti-RBD IgG and 70% had anti-S -IgG. These antibodies had moderate neutralizing activity. Patients characteristics were further explored to find out that individuals with longer stays in hospital had more neutralizing activity of the antibodies. Subtle differences were also observed for neutralizing activity in males vs females. The authors have also checked the frequency of RBD specific cells in six individuals ranged from 0.07% to 0.005% of all circulating B cells and examined their amino acid sequences which were found to be nearly identical in different individuals. The authors further developed monoclonal antibodies from RBD specific clones and found that they had potent neutralizing activity. Can these antibodies be used as therapy? Yes, but they are expensive and need to be tested as a drug as antibodies can also lead to disease enhancement as seen in dengue that had impeded dengue vaccine development. 

Authors in this study have primarily focused on two viral proteins. It might be speculated that as antibodies to other SARS-COV-2 proteins are being explored for their neutralizing activity, the potency of the convalescent plasma will amplify. Antibodies is what our hopes rely for most vaccines and they will be an important consideration for an effective vaccine against SARS-CoV-2. This study has reported anti SARS-COV-2 antibodies have convergent and reasonable neutralizing potency but can be further therapeutically exploited for memory B cell clones. As others like Eliza beeline outside blood centers to bleed 600 micro liters of elixir of life to pump life back into someone’s blood, they have a convincing evidence to feel content and satisfied on the promise of their gift which is far from being futile. 

For original article click here. 

Written by Navvy Kaur

Immunologist, Informatician, trying to learn some machine learning and grasp few mathematical concepts.