Stress and Depressive and Anxiety Symptoms in the General Population and in SARS-CoV-2-Infected Patients—Findings from a Population-Based Three-Wave Study

Round 1

Reviewer 1 Report

This is an interesting study, with potentially valuable insights. I was really intrigued by the topic and liked the fact it was a three time points repeated measures design. However, I found the methodology section rather confusing, and I believe there are some important pieces of information missing. First of all, a flow chart/diagram of the study would be useful: for each time point the sample size should be reported: it is very unlikely that there were no dropouts during the time period of the 14 months between the first and the last evaluation. But more importantly, it is almost impossible that none of the participants who initially reported not having been infected, remained uninfected throughout the study.  I did not find any information in the description of the procedure that they were asked that in T1 and T2 time points? How were these cases treated? Were they then allocated into the other group? Again, a flowchart clearly stating this would be useful.

If this was not accounted for, then we cannot conclude with any certainty that the groups did not in fact differ in the outcome measures.

Furthermore, why was the severity of the symptoms not included as a predictor for the sample of participants who did report SARS-CoV-2 infection? It has been shown (and the authors even mention these findings) that a more severe form of infection increases the risks of anxiety and depression subsequently.

Instruments: none of the psychometric characteristics of the questionnaires are reported (at least the reliability coefficients should be reported). For the two-item versions of the scale, they might be low, but other indicators of the instruments validity can be presented.

Line 168 - standard divisions – this is probably a typo (standard deviations?)

Figure 1: please label full name of the group (not just group 1, 2) so that the figure is easily understandable without having to look into the text. Also, there were only 3 time points, and the figure suggests there were more (0.5 and 1.5 in y axes) – I understand that this is the software’s output, but it is misleading.

In the interpretation of the results, the phrases such as „statistically non-significant and negative effect” or “effect of sample non-significant and positive” - are also misleading. If an effect is statistically insignificant, it implies it does not exist (it is observed by chance) and thus it cannot be interpreted as either positive or negative.

In the limitations section, the authors state that “The self-report nature of our measures regarding stress and depressive and anxiety symptoms could have been sensitive for under- or over- reporting of symptoms” – in theory, this statement goes for any given self-report measure. However, when measuring one’s perception of stress or anxiety, that statement is rather strange: who can judge one’s own perception of a stressful event better than the participant themselves? There is no objective measure for this (even the physiological measures of arousal during the stressful events show such a large interindividual variability that they are not objective indicators of stressfulness of an event for each specific participant).

minor editing needed 

Author Response

Dear Reviewer,

Thank you for taking the time to review our study and provide valuable feedback. We appreciate your interest in our research and addressed your comments and concerns point by point.

1. Flow Chart/Diagram: We agree that a flowchart or diagram outlining the study's progression and sample size at each time point would be beneficial. We incorporated this into the revised manuscript to enhance the clarity of the methodology. (see Fig. 1)
2. Handling of Participants Reporting No Infection: You raise a valid point regarding participants initially reporting no infection remaining uninfected throughout the study. We apologize for not including this information in the initial description. Participants who reported infection at T1 (n=6) and T2 (n=28) were actually excluded because we could not confidently confirm infection based on self-report. We clarified this process in the revised methodology section.
3. Severity of Symptoms as a Predictor: Your suggestion to include the severity of symptoms as a predictor for participants who reported SARS-CoV-2 infection is valuable. We acknowledge that symptom severity can affect mental health outcomes. Nevertheless, we unfortunately cannot include symptom severity as a valid variable because it was not asked for each symptom individually. We have now commented on this in the limitations.
4. Psychometric Characteristics of Questionnaires: We appreciate your concern regarding the lack of reported psychometric characteristics of the questionnaires. In our revised manuscript, we included information on reliability coefficients and to ensure the robustness of our instruments. PHQ-4 at baseline: McDonalds omega, ω = .83; PSQ at baseline: McDonalds omega, ω = .93
5. Typo Correction (Line 168): Thank you for pointing out the typo in our manuscript (standard divisions instead of standard deviations). We corrected this error in the revised version.
6. Figure 1 Labeling and Axes Misleading: We revised Figure 1 (now Figur 2) for clarity and eliminated any misleading aspects related to the axes. Full group names can be found in the notes below the figure. We understand the importance of clear visual representation.
7. Interpretation of Results: We appreciate your clarification regarding the interpretation of statistically non-significant effects. We now ensured that our interpretations accurately reflect the statistical significance, avoiding any misleading terminology.
8. Limitations Section: We understand your point about the self-report nature of measures. We revised the limitations section to provide a clearer context for the statement, highlighting the challenges of self-report measures and their potential for bias in the assessment of stress and mental health symptoms.

Thank you once again for your thoughtful review. Your feedback helped us improve the quality and clarity of our manuscript.

Reviewer 2 Report

The study analyzed the relationship between the pandemic and SARS-CoV-2 infection with stress, anxiety, and depression. While the study is exciting and essential to the field, some limitations exist. There is no description of statistical analysis in the methods section. The way the results are described could be more explicit. Discussion can be improved. The biological factors associated with manifestations of psychiatric symptoms could be addressed.
Regarding data from the general population, it is a significant limitation that no tests prove non-infection. What about the infected population? How long after infection was the study conducted? This could influence the results.

Author Response

Dear Reviewer,

We sincerely appreciate your thoughtful review of our study. Your feedback is invaluable, and we addressed your comments to improve the quality of our work. Below is a point-by-point response to your concerns:

1. Lack of Description of Statistical Analysis: We acknowledge the oversight in not providing a detailed description of the statistical analysis in the methods section. In the revised manuscript, we provided a comprehensive explanation of the statistical methods employed to enhance the clarity and transparency of our methodology. In the previous version of the manuscript, much of the description was in the results section. We have now moved it.
2. Clarity of Results Description: We appreciate your feedback on the clarity of our results description. In the revised manuscript, we tried to ensure that the presentation of results is more explicit, with clear explanations of the findings to facilitate better understanding for readers. In addition we moved the description of statistical analyses in the method section.
3. Improvement of Discussion Section: We understand your suggestion for improving the discussion section. However, we are afraid the possible biological factors associated with the manifestation of psychiatric symptoms related to the pandemic and SARS-CoV-2 infection are outside of our scope.
4. Testing for Non-Infection in General Population: Your concern regarding the absence of tests to prove non-infection in the general population is a valid point. We already included a discussion of this limitation in the manuscript, emphasizing that the lack of such testing may introduce an element of uncertainty into the interpretation of the results.
5. Timing of the Study After Infection: We appreciate your point about the timing of the study relative to infection. The duration between infection and the study could indeed influence the results. Unfortunately we cannot specify the infection dates from the data but the baseline measurement took place shortly after the first registered SARS-CoV-2 infection in Germany. We put this information in the Limitation section. Nevertheless, we believe the results are exciting since the baseline measurement was conducted at a very early stage compared to other population-based studies.

Once again, we sincerely thank you for your constructive feedback.

Regards,

Marius Binneböse

Round 2

Reviewer 1 Report

Thank you for taking your time to address my concerns. The revised version of the manuscript is more informative than the previous one. There are many limitations, but they are adequatelly addressed.

English is fine.

Author Response

Thank you for your kind response.

Reviewer 2 Report

The article has been properly revised and can be accepted for publication.

Author Response

Thank you for your kind response.