Rapid Clinical and Radiological Improvement in a Patient with Severe COVID-19 Infection Treated with Convalescent Plasma

Round 1

Reviewer 1 Report

The Reviewer appreciates Authors’ efforts on demonstration the positive curing effect from the convalescent plasma. This report can be published after addressing the following comment:

Authors mention that the patient was injected not only with convalescent plasma, but also with dexamethasone. However, they do not discuss the possibility that the curing effect was due to this drug and not due to the plasma alone. Please discuss it.

Author Response

I agree. This is a confounding factor 

Reviewer 2 Report

The manuscript with the title: Rapid clinical and radiological improvement in a patient with severe COVID19 infection treated with convalescent plasma. by Waleed Ghannam et al. describes the case of a 29-year-old man with COVID 19 who was admitted to the emergency department with pneumonia symptoms. He was treated with 2 doses of convalescent plasma and experienced a dramatic improvement in his pneumonia symptoms.

The manuscript deals with a very important and urgent topic due to the current situation. Nevertheless, I have a few comments.

Line 22: there is missing a point at the end of the sentence after reference 9

Line 28: please write it with SI Units 38.2 °C

Line 37: please write out od the first time you used it

Line 37: please add a reference for the protocol because it is important for the case to show the used antibody titer in the convalescent plasma used.

Line 50: The sentence sounds uncommon. I would write it as followed: Despite this severe process, he responded quickly to therapy including convalescent plasma, and was discharged two days after admission with a normal chest x-ray.

Line 54: How can you explain that the effect in this patient was so dramatic although he was treated with convalescent plasma only after day 10?

Figure 2 caption: convalescent plasma

Were no blood tests performed after 1 month? It would have been interesting to know whether the D-dimer value is still elevated. From the statements, the patient does not appear healthy by far after 1 month. The symptoms seem like a "long covid" disease. Are there any possible explanations for the symptoms that continue to be noticeable?

Are there patients with COVID19 symptoms who were also treated with dexamethasone as well as enoxaparin without convalescent plasma treatment? This would be very useful as an interesting control example to determine the effect of convalescent plasma treatment properly.

In view of the current study situation with mixed research statements in the various studies, this case report is very interesting. The question of meaningfulness is of course given with the presentation of a single patient. Unfortunately, the initial parameters measured were not repeated after 1 month to guarantee a direct comparison and improvement of the blood values. Due to the fact that the patient still has severe symptoms after one month (although no further pneumonia), the question of the effects of the treatment with convalescent plasma is also given.

These aspects should be discussed and incorporated in the discussion.

Author Response

A new version has been submitted  

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors have incorporated the requested changes to the greatest extent possible. The general debate now seems more solid and is heading in the right direction.

Author Response

The period in time when the patient was admitted was at the height of the first wave of Covid-19 admissions in Israel. Our medical center had an aggressive policy of discharges in order to make available as many beds as possible. The treatment was supported by community care from the patient’s HMO.

The fact that the patient received plasma after the first few days of his illness probably explains the long covid symptoms, which were not described at that time.

Liver enzyme elevations are now well described in Covid-19 infection, but only 6.4% had severe liver injury in one study ( Anastasiou OE et al Digestive Diseases 2020).

Our protocol for treating patients with severe Covid-19 included checking D-dimer levels at admission and appears  on line 78 but they were not repeated after discharge. Dexamethasone was also part of the protocol  in view of the beneficial effect that had been reported in the literature. Its main effect seems to be in increasing the number of ventilator-free days, but not on mortality (Tomazini et al JAMA 2020). A recent paper in the NEJM (RECOVERY collabrative group) found a positive effect in decreasing the need for mechanical ventilation  and mortality.  This trial randomized patients to different arms one of which included convalescent plasma but not combined therapy. A subsequent paper by Joyner et al  showing the importance of plasma with high titer antibodies in reducing mortality was not related to administration of steroids. Half of the patients in the different titer groups received steroids and the effect of high titer plasma versus low titer was significant. This suggests that the role of plasma is independent of steroids. We cannot dissect out the relative contribution of dexamethasone versus plasma in this patient but we think this case underlines the importance of plasma as a therapeutic modality. This is now very relevant for countries in South America and India that are overwhelmed with Covid cases.

We have  corrected the grammatical errors and thank the reviewer for bringing this to our attention.