The Multisystem Impact of Long COVID: A Comprehensive Review

Response to Reviewer 1 Comments

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions highlighted (yellow) in the re-submitted revised manuscript. Also, small corrections have been made in English, and they are marked in yellow background.

Comments 1: The definition used for long COVID is very important for the current research. The following statement needs an abbreviation "The description given for Long COVID by the World 48 Health Organization (WHO) ..."

Response 1: Thank you for the observations. I made the necessary changes. “Long COVID, according to the World Health Organization (WHO), represents any clinical manifestation, present in the first three months after acute COVID-19, minimally evolving over two months, without another identifiable cause [1].” Please see L47 of the main manuscript.

Comments 2: Also, the terms used for the literature search is very important. How were the following terms chosen? ""cardiovascular diseases or renal diseases or respiratory diseases or gastrointestinal diseases or neuro-psychiatric diseases or endocrine diseases or skin diseases or pathology or dysbiosis or chronic fatigue syndrome or myalgic encephalomyelitis."

Response 2: The selection of terms used in the literature search was carried out carefully and in line with our research objectives on long COVID syndrome. The terms were chosen to encompass a broad range of possible manifestations associated with this syndrome.

Comments 3: The guidelines for systematic reviews demand that the search should be done in at least 2 databases, it looks like only one was used: the name Pubmed via Medline should be noted in Materials and Methods (search in Scopus or Web of Science is advisable).

Response 3: Thank you for your observation. The research was conducted on several databases. Scopus and Web of Science databases were omitted by mistake during writing. Please see L68-69 of the main manuscript.

Comments 4: It's not clear how was the information from the 167 articles searched. What kind of data were extracted.

Response 4: Related information about various clinical manifestations reported on various systems was extracted, looking for data about the mechanisms underlying these manifestations.

Comments 5: The conclusions seem too general for a synthesis of literature. Maybe more precise ideas could be summarized. Also, it could be useful a Table with all possible long COVID clinical manifestations could be summarized (with reference for each of the symptoms listed). 

Response 5: Thank you for the observation. At your request and that of the second reviewer, we have added a graph with the requested clinical data (please see newly added Figure 6).