Review of: "Proposal to Explain the Cause of Long COVID Based on the Concept of Host Factor Variants"
Résumé
Clarity and Structure of Hypothesis:The central hypothesis regarding the role of host factors, including MHC polymorphisms and antigen-presenting cells (APCs), in long COVID is compelling but lacks clear progression and structure in the manuscript.The hypothesis could benefit from a more concise summary in the introduction to guide readers through the rest of the paper.Recommendation: Revise the introduction to better articulate the main hypothesis, perhaps providing a brief outline of the specific mechanisms proposed (e.g., MHC variability and its implications for viral persistence). Lack of Direct Evidence for Long COVID Mechanism:Although the paper provides a solid theoretical framework linking MHC polymorphism and APC function to long COVID, there is a lack of direct experimental evidence or references supporting this explanation in the specific context of long COVID.Most of the data presented are based on general viral infections.Recommendation: Either conduct or reference specific studies on long COVID pathogenesis in relation to MHC polymorphisms or clearly state this as a proposed model/theory rather than a proven explanation. Mechanistic Ambiguity Regarding APCs and Viral Persistence:The manuscript presents macrophages and dendritic cells as potential long-term reservoirs of viral particles, leading to persistent symptoms.However, the paper is unclear on whether this viral persistence in APCs is a recognized mechanism in long COVID.Recommendation: Clarify the current evidence supporting viral persistence in APCs specifically in the context of long COVID.If speculative, clearly differentiate between what is known and what is hypothesized. Overuse of Hypothetical Terminology:There is a recurring use of terms such as "might," "could," and "possibly," which weakens the scientific rigor of the arguments presented.
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