(For a better understanding of this post, read some key concepts of evidence-based medicine applicable to COVID-19.)

 

KEY MESSAGE

Today it is not possible to say whether convalescent plasma is or is not an effective treatment for COVID-19. There are two reasons for this: (1) there are still no studies that specifically assess its effects in COVID-19 and (2) the studies that evaluate its role in other infections, and whose information could be extrapolated to COVID-19, provide evidence of very low certainty.

 

This means that, when balancing the pros and cons of this treatment, there is not enough reliable information, so it is likely that different organizations will provide dissimilar recommendations. Surely, some will recommend not to use convalescent plasma and wait for the evidence to be clearer, while others will propose to consider its use only in critically ill patients or in those at high risk of aggravation.

 

Based on: No direct evidence available. Indirect evidence of VERY LOW CERTAINTY, from other coronavirus infections.

 

What is convalescent plasma?

Patients who have recovered from other infections have antibodies in their blood that protect them from future illnesses caused by the same infectious agent. These antibodies can be obtained from the blood plasma, which in this context is called convalescent plasma.

 

The transfusion of convalescent plasma to a person with a viral infection could neutralize the pathogenic microorganism and, thus, give that person time to mount an active immune response, that is to say, a response generated by her own immune system.

 

Where does the interest in convalescent plasma for COVID-19 come from?

Some believe that this therapy played a fundamental role at the time when there were no effective vaccines or medications for most diseases. As we are precisely in this situation today against COVID-19, interest in using it has resurfaced. But if we had an efficient vaccine or drug today, the option of using convalescent plasma would probably not be considered, because there are practical difficulties in obtaining it and, consequently, its availability is limited. The main idea to keep in mind is that convalescent plasma could be an alternative for the treatment of COVID-19 while scientists discover a better option.

 

What does the evidence on convalescent plasma in COVID-19 tell us today?

After conducting an exhaustive search for evidence (systematic review), with the help of the international team COVID-19 L·OVE Working Group, we did not find any studies that meet the minimum requirements to estimate the effect of convalescent plasma on COVID-19.

 

In the absence of direct evidence in COVID-19, it is sensible to extrapolate the information from other similar coronavirus infections, such as those caused by SARS-CoV and MERS-CoV. But, although we identified some studies evaluating convalescent plasma in these cases, the conclusions they provide constitute very low-certainty evidence. In other words, it is not possible to infer from them whether or not convalescent plasma will be effective in treating COVID-19.

 

Will we get more information on convalescent plasma for COVID-19 in the near future?

Yes. There are already at least 12 ongoing randomized trials evaluating the use of convalescent plasma in patients with COVID-19, particularly in the most severe patients.

 

When making a decision, what factors should go on the balance?

There are decisions we must make even when there is not enough evidence. For decision-makers to proceed in the best possible way, the following factors must be put on the balance: scientific rationality, benefits, risks, costs, and other aspects (detailed below).

 

Scientific rationality: The basic premise that supports the use of convalescent plasma is simple and well-founded.
Benefits: The existing evidence does not yet make it possible to draw any conclusions. We do not have direct evidence. Indirect evidence – the evidence which we can extrapolate from other similar diseases – has many limitations.

Risks: The risks of plasma transfusion are well known. The most common are allergic and anaphylactic reactions, which are low in frequency but can cause acute lung injury or other serious complications.

Costs: The total cost associated with the use of human plasma is high, especially if the capacity to obtain, process and maintain it is not installed.

Other things to consider: Even if all recovered patients were fit and willing to donate plasma, the amount of convalescent plasma that could be produced is not enough to treat all patients with COVID-19, so it would probably be necessary to establish some prioritization mechanism. Eventually, as more patients recover, availability will also be higher.

 

In summary, the arguments for and against using convalescent plasma to treat COVID-19 are:

 

For	Against
Scientific rationality: Well-founded Risks: Small-scale	Benefits: Uncertain Other aspects to consider: Limited availability Costs: High

 

CONCLUSION

The available evidence to decide what role to assign to convalescent plasma in the treatment of COVID-19 is of very low certainty. This means that it cannot be stated whether it is effective or not.

 

Now, the evidence alone (or the lack of evidence) is never enough to make decisions. In this case, the balance between the pros and cons of this treatment is not well informed, nor is it definitive, so it is likely there is some variability in the recommendations delivered by scientific societies. 

We estimate that the range of recommendations that we should expect with the currently available information ranges from not using it, except in the context of a randomized controlled trial, to using it in selected cases, such as those of greater severity.