To the Editor:
I have read the article titled “SARS-CoV-2 symptomatic reinfection among patients with primary antibody deficiency” by Marcus et al1 with great interest. I have several questions/concerns about their reinfected immunodeficient cases and managing these patients.
Reinfection risk is a particular concern in immunodeficient patients due to their incapability to produce sufficient protective antibodies, and they may have an amplified risk for SARS-CoV-2 reinfection. Loh et al2 first time described possible SARS-CoV-2 reinfection in a patient with X-linked agammaglobulinemia (XLA).
First, were their cases of real reinfections or just simple chronicity (persistence) of SARS-CoV-2 infection?3 , 4 Also, antibody-deficient patients are well known to experience chronic infection with some types of viruses, for example, Epstein-Barr virus, cytomegalovirus, and so on. Ameratunga et al5 demonstrated that patients with primary immunodeficiency, including common variable immune deficiency, have been described with sustained viral shedding, termed “chronic COVID-19.” There are 3 patients with XLA and patients with XLA who are recognized as unable to produce sufficient antibodies to clear SARS-CoV-2 causing persistent/chronic infection.1 Is not this more probable? Do the authors know that their reinfected cases were infected with the same or different variants of SARS-CoV-2?
I think that the authors are better to explain/speculating real mechanisms of recurrence (persistence) in these patients. The possible laboratory causes mentioned in the literature are the following: the polymerase chain reaction test may have stayed positive for some time after the initial infection, or tests might be occasionally negative if the viral concentration was low in the test material.2
Second, how do they explain the very high reinfection rate (42%) in their cases? Most of their cases did not have comorbidity or combined immunodeficiency. Could this be a reason not to use antivirals, for example, remdesivir for initial infection?1
Remdesivir monotherapy was found by Brown et al3 to be associated with continued viral clearance in 30.4% of incidents, whereas the combination of remdesivir with convalescent plasma or anti–SARS-CoV-2 monoclonal antibody caused viral clearance in 92.8% of incidents. Patients taking no treatment did not clear SARS-CoV-2.3 Their initial treatment did not include antiviral, monoclonal antibody, or convalescent plasma, except for one.1 Although the optimal treatment remains unknown, they have demonstrated that the combination of antivirals and antibody-based treatment modalities are highly effective to clear SARS-CoV-2.3 Ameratunga et al5 also reported that intrahost viral progression in “chronic COVID-19” could result in the appearance of treacherous vaccine-evasion variants resistant to monoclonal antibodies. For example, did their case 4 benefit from monoclonal anti–SARS-CoV-2 antibodies?1
The authors confessed that they saw a very high reinfection rate despite regular immunoglobulin replacement. Did they use the same brands of immunoglobulin preparations produced in Israel in every case? For instance, some brands from abroad are known for high titers of anti–SARS-CoV-2 antibody titers.6
Third, the authors did mention the vaccination status of the patients and said that none of the described 5 patients received the mRNA vaccine.1 How about the other vaccine types? Here, another important issue is whether there is any effect of being unvaccinated on reinfection? Do they advise vaccinating these patients?
Fourth, there is no explanation anywhere in the article for the abbreviation of CCT 24.1 What does it mean?
In conclusion, can we also add not being able to use antivirals, one of the monoclonal antibody therapies, and being unvaccinated increased the chance of reinfection in their patients? I think that the authors should have also discussed the management (therapeutic modalities, eg, antivirals, vaccinations, etc) of these kinds of patients briefly, especially those having comorbidities.
Footnotes
No funding was received for this work.
Conflicts of interest: The author declares that he has no relevant conflicts of interest.
References
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