Diversity and clinical correlations of SARS-CoV-2 variant during the introduction of the Delta variant in Guatemala
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic surveillance is crucial for understanding viral evolution and guiding public health responses. However, many countries, particularly in Central America, have limited sequencing capacity, resulting in scarce and delayed data. This study addresses this gap by analysing 320 SARS-CoV-2 genomes sequenced from a major diagnostic centre in Guatemala City, Guatemala, between April and August 2021. Clade 21J (Delta) was predominant (46.2%), followed by 19B (29.4%) and 20J (Gamma, 6.6%). The most reported symptoms were cough, headache, malaise and myalgia/arthralgia. Among patients infected with the Delta variant, 39.9% reported being contacts from a confirmed case, less than reported by the patients infected with non-Delta variants (53.2%, P =0.017). The proportion of signs and symptoms was similar among these two groups, except for the history of fever, which was increased by ~twofold in the Delta group. This research contributes valuable genomic and epidemiological data to elucidate SARS-CoV-2 variant dynamics in Central America and emphasizes the importance of global genomic surveillance for pandemic preparedness and response.
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Editor Decision Phrases The work presented is clear and the arguments well formed. This study would be a valuable contribution to the existing literature. This is a study that would be of interest to the field and community.
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I apologise for the delay in getting this back to you, and appreciate your patience. The work presented is clear and the arguments well formed. This study would be a valuable contribution to the existing literature. However the reviewers have highlighted some minor concerns with the work presented. We would greatly appreciate if you can address all their comments.
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Comments to Author
The manuscript describes genetic analysis of SARS2, primarily focused on spike region, from clinical isolates collected retrospectively between April 2021 and August 2021 at a diagnostic center in Guatemala. The introduction section accurately highlights the knowledge gap and potential bias in existing genomic surveillance data driven by infrastructural challenges in the early phase of the pandemic. A problem that can have consequences on a larger scale at times of public health emergency and is highlighted by the authors. However, Contradictory to the problem statement, the last paragraph of this section mentions that the government of Guatemala has sequences a substantial number of genomes that may or may not have appropriate representativeness. Unfortunately, this is not further elaborated in …
Comments to Author
The manuscript describes genetic analysis of SARS2, primarily focused on spike region, from clinical isolates collected retrospectively between April 2021 and August 2021 at a diagnostic center in Guatemala. The introduction section accurately highlights the knowledge gap and potential bias in existing genomic surveillance data driven by infrastructural challenges in the early phase of the pandemic. A problem that can have consequences on a larger scale at times of public health emergency and is highlighted by the authors. However, Contradictory to the problem statement, the last paragraph of this section mentions that the government of Guatemala has sequences a substantial number of genomes that may or may not have appropriate representativeness. Unfortunately, this is not further elaborated in discussion and makes the objectives of the work confusing to the reader. Authors may consider clarifying that. Materials and methods part is detailed, scientifically accurate and well-referenced. The primary pool of samples includes approximately 4000 nasopharyngeal swabs positive for SARS-CoV 2 as determined by a commercial RT-PCR kit. A Ct value of 30 is decided as the threshold of exclusion. Authors argue that this is necessary to achieve a high sequence quality for a full genome sequence. While I agree with the decision, I request the authors to provide a reference for that. Knowing that more complex assays such as virus isolation are possible at Ct values as high as 35. Following the exclusion of negative samples and positive but low viral RNA, authors randomly select 12% of samples for gene amplification and sequence analysis. Results section begins with a description of demographics and clinical profile of the cohort. While this is a simplistic approach to link clinical manifestation with disease outcomes, I find it a key strength of the work and a great demonstration of how clinical entities and molecular virologists can work together. However, It's unclear how these clinical data were collected. Are they self-reported by the patients and those records are kept at a diagnostic center? Or are those from clinician files. I request the authors to clarify that and provide an example/template of the clinical questionnaire form as a supplemental file. A major concern in describing dominant variants is the exclusion criteria leading to the impression that SARS2 spread followed a seasonal/time dependent pattern in mid2021 as shown in Figure2. It's most likely not the case. To address this the I recommend that the authors include a comparison plot of all positive samples to clarify that. It is also important to warn the readers against possible biases with respect to selection criteria. This needs to be added to the paragraph that describes limitations (Line 302). Overall, the manuscript may lack significant novelty and may not add substantially to the existing body of knowledge/evidadnce, but it certainlyconveys an important message on the importance of genomic surveillance from under-represented regions and can attract readers. The study is conducted using a scientifically sound approach, Other comments: Line 82: Please name the center. Line 83: Guatemala is written twice. Line 90 and 92: Please write the number of excluded samples in this line. Line 91: Please clarify what duplication and discrepant results mean. Line 93: Please write the number of samples for the 12%. Line 171: Please provide a description of missing regions. Line 200: Please describe how 'Other' category was defined. Table 2: How is the history of fever different from fever? Please describe. Line 336: Please ensure that the accession numbers are accurate. Some show unrelated sequences. Also please clarify how many sequences are submitted. Please provide ethics approval number.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Many thanks for authors for their submission on the diversity and clinical correlations of SARS-CoV-2 variants in Guatemala, with a focus on the introduction of the delta variant. Abstract Very well written. Puts the research nicely into context and informs the reader on the main findings of the research. Introduction Overall, I think the Introduction is excellent. Very well thought out and structured. I only have a few comments that the authors may consider. I would also have no issue if they are not adapted, as References for the points are stated in the manuscript and the reader can find the data themselves if they so wish. Line 47 - Perhaps state the year, March 2020. Line 49 - Perhaps state the month, January 2020 Lines 60-61 - The substantial burden can be made more impactful with statistics …
Comments to Author
Many thanks for authors for their submission on the diversity and clinical correlations of SARS-CoV-2 variants in Guatemala, with a focus on the introduction of the delta variant. Abstract Very well written. Puts the research nicely into context and informs the reader on the main findings of the research. Introduction Overall, I think the Introduction is excellent. Very well thought out and structured. I only have a few comments that the authors may consider. I would also have no issue if they are not adapted, as References for the points are stated in the manuscript and the reader can find the data themselves if they so wish. Line 47 - Perhaps state the year, March 2020. Line 49 - Perhaps state the month, January 2020 Lines 60-61 - The substantial burden can be made more impactful with statistics on the case fatality rates in Latin America, if that data is available. Lines 63-64 - Similar to above, if data is available on the incidence of SARS-CoV-2 it should be included to illustrate the burden in Guatemala Materials and Methods Line 83 - Should this have read Guatemala City, Guatemala? Lines 88-89 - It would be helpful to note exactly how the random selection occurred. Lines 90-92 - The exclusion of samples with Ct Values >30 is stated twice. Would consider removal of Line 90, and leave Line 92, and change it to, "…achieve the highest number of quality samples…" Results Very well presented. Lines 156-157 - What percentage was most patients? Lines 157-158 - Personally, I would report the percentage of symptomatic individuals and not the asymptomatic. Table 1 - I believe you meant to translate "Disnea" to English? Dyspnoea. Line 206 - How was a contact from a confirmed case defined? Discussion Well written and researched with inclusion of relevant studies and comparisons. Lines 238-240 - Please review your sentence. Line 277 - "dyspnoea" The paper is well presented and will be a valuable contribution to the body of literature on genomic epidemiology, especially from LMICs.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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