A New HRCT Score for Diagnosing SARS-CoV-2 Pneumonia: A Single-Center Study with 1153 Suspected COVID-19 Patients in the Emergency Department

Round 1

Reviewer 1 Report

Thank you for this interesting manuscript about CT score in COVID 19 pneumonia.

This score evaluate both lung disease estension and specific lung abnormalities.

Abstract line 24: baseline ground glass opacities

M&M HRCT: Pts examined... repeated sentence

Line 192: size of the lymph nodes, I cannot understand, something need to be changed

Line 246: a significantly higher rate of in- hospital deaths. I cannot understand this second part of the sentence. Rephrase it.

Line 258: crazy paving pattern

Line 298: that it be limited. Modify, for example"that it need to be limited" or in another way.

Author Response

Reply: Dear Reviewer, Thank you for your time and valuable comments, which can have a significant impact on the quality of our work.

Abstract line 24: baseline ground glass opacities

reply: thank you for this. We corrected this typo. 

M&M HRCT: Pts examined... repeated sentence

reply: Again, thank you for this. we recognised the repeated sentences and removed it. 

Line 192: size of the lymph nodes, I cannot understand, something need to be changed

reply: thank you for this, the sentence was wrongly written. we rephrased it as follows: “Presence of several lymph nodes with a diameter of at least 10 mm” 

Line 246: a significantly higher rate of in- hospital deaths. I cannot understand this second part of the sentence. Rephrase it.

reply: Thank you again. we rephrased the sentence as follow: “COVID-19 patients had significantly higher levels of interleukin 6 (IL -6), fibrinogen, lactate dehydrogenase (LDH) and ferritin and a significantly higher rate of in-hospital death (16.7% vs. 9.1%, p-value 0.001) (see Table 1)”. 

Line 258: crazy paving pattern

reply: amended

Line 298: that it be limited. Modify, for example"that it need to be limited" or in another way.

 reply: amended as suggested.

Reviewer 2 Report

In this article, Sofia et al reported the single centre retrospective study to develop a radiological score to predict the probability of COVID-19 with HRCT. Huge number of 1153 patients were enrolled in this study. The number of segments with baseline glass opacities (OR 1.18, 95% CI 1.11-1.26), number of segments with linear opacities (OR 1.21, 95% CI 1.05-1.42), crazy paving patterns (OR 6, 95% CI 3.79-9.76) and vascular ectasia in each segment (OR 2.46, 95% CI 1.1.5-5.8) were included in the score. The HRCT score showed high discriminatory power (Area Under the ROC Curve of 0.8267 [95% CI 0.8-0.85]) with 72.2% sensitivity, 86.6% specificity, 78% PPV, and 83% NPV for its best cut-off. They concluded that the HRCT score has good diagnostic and discriminatory accuracy for COVID-19 and is easy and quick to perform. I have some questions as follows.

major concerns)

1) Although there are many studies on whether HRCT score is related to the severity of COVID-19 infection, this study differs from those studies in that you are investigating whether HRCT score can predict COVID-19 infection by calculating HRCT score in patients with suspected COVID-19 infection. If the HRCT score is high, according to the results of this study, COVID-19 infection is strongly suspected, and therefore, even if the COVID-19 test is negative, it is considered necessary to repeat the antigen and PCR tests. If the test is positive, a therapeutic agent targeting COVID-19 can be used, so there may be merit in repeating the test for those at high risk of infection. In this study, were there any cases in which the diagnosis was not made by one test and the PCR or antigen test was repeated several times?

2) In table 1, in the SARS-CoV-2 negative group, the mean sBP was 120 ± 26 mmHg; in the SARS-CoV-2 positive group, the mean sBP was 121 ± 17 mmHg. The p-value concerning differences in these groups was statistically significant. However, there does not appear to be much difference in the figures. Could this be a calculation or notation error? Please check again.

3) Also, in table 1, many tests have been performed, so multiple comparisons need to be corrected (e.g. Bonferroni correction). Additional analysis is requested.

minor concerns)

1) In Figures 1, 2, 4, 5, and 6, the term "HRCT" was mistakenly used instead of "HRTC". Please correct appropriately.

2) In table 1, "fibrinogeno" may be mistaken for "fibrinogen" and "Ferritine" for "Ferritin". Please correct appropriately.

3) In line 228, "odd ratios" seems to be a mistake for "odds ratio". Please correct appropriately.

I have described some mistakes in minor concerns as far as I am aware.

Author Response

First of all, we would like to deeply thank the reviewer for his valuable comments that stimulated us to introduce important adjustments in our work, significantly improving its quality. 

Here is a point by point response to your precious suggestions.

major concerns

1) Although there are many studies on whether HRCT score is related to the severity of COVID-19 infection, this study differs from those studies in that you are investigating whether HRCT score can predict COVID-19 infection by calculating HRCT score in patients with suspected COVID-19 infection. If the HRCT score is high, according to the results of this study, COVID-19 infection is strongly suspected, and therefore, even if the COVID-19 test is negative, it is considered necessary to repeat the antigen and PCR tests. If the test is positive, a therapeutic agent targeting COVID-19 can be used, so there may be merit in repeating the test for those at high risk of infection. In this study, were there any cases in which the diagnosis was not made by one test and the PCR or antigen test was repeated several times?

reply:  very thank you for this comment.You have brought out perfectly the essential point of our study. It is valuable radiological and clinical data that can play an important role in the management of patients with suspected COVID -19. As mentioned in the introduction and as already known, the sensitivity of the Sars-Cov2 test is less than 100% and many false negative nasopharyngeal swabs have been found in clinical practise. In our hospital, according to the local protocol, nasopharyngeal swabs were repeated in patients with high suspicion of COVID -19.In our study, nasopharyngeal swab was repeated at least once in 327 patients (28.36% of total): once in 229 cases (70% of repeated swabs ), twice in 63 cases (19.3% of cases), more than twice in 26 patients (7.9%). Finally, a positive nasopharingeal swab for SARS-CoV2 was found in 58 of 315 patients (18.4%). Considering only the patients who underwent to a repeated swabs, those who  tested positive for SARS-CoV2 infection had a significantly higher HRCT score (median 6.01 [IQR 0-11.81] versus 0 [IQR 0-3.54], p0.001).

According to your suggestion, this is a particularly interesting data for our readers, so we decided to include the following in the results section, as follows: “A nasopharyngeal swab was repeated at least once in 327 patients (28.36% of total): once in 229 patients (70% of repeated swabs ), twice in 63 patients (19.3% of cases), and more than twice in 26 patients (7.9%). Finally, a positive nasopharyngeal swab for SARS-CoV2 was found in 58 of the 315 patients (18.4%).” page 9, lines 236-239 and 

“ Considering only patients who underwent repeated swabs, those who tested positive for SARS-CoV2 infection had a significantly higher HRCT score (median 6.01 [IQR 0-11.81] versus 0 [IQR 0-3.54], p<0.001).” page 10, in lines 262-264

2) In table 1, in the SARS-CoV-2 negative group, the mean sBP was 120 ± 26 mmHg; in the SARS-CoV-2 positive group, the mean sBP was 121 ± 17 mmHg. The p-value concerning differences in these groups was statistically significant. However, there does not appear to be much difference in the figures. Could this be a calculation or notation error? Please check again.

Reply: Thank you for noticing that. As you indicated, it is an error in reporting. All data has been checked and the reporting error has been corrected.

3) Also, in table 1, many tests have been performed, so multiple comparisons need to be corrected (e.g. Bonferroni correction). Additional analysis is requested.

Reply: thank you also for this suggestion. As far as we know, the Bonferroni correction is the adjustment required for two or more statistical tests of the difference between two means on the same sample or for two or more statistical analyses on the same sample of data. When multiple hypotheses are tested, the probability of observing a rare event increases, and so does the probability of falsely rejecting a null hypothesis (i.e. making a Type I error). However, there are many criticisms of the Bonferroni correction and it is considered unnecessary or too conservative when there are a large number of tests and/or the test statistics are positively correlated (e.g. in the case of correlation and regression analyses). The Bonferroni correction has the disadvantage that it increases the probability of false negative results and thus reduces the statistical power (Nakangawa, S. A farewell to Bonferroin: the problems of low statistical power and publication bias. Behavioural Ecology, 15(6), 1044-1045). Perneger reported in 1998 that Bonferroni corrections are at best unnecessary and at worst harmful to sound statistical inference. The Bonferroni correction examines the universal null hypothesis in which two groups are identical on all variables examined at the same time. However, this type of null hypothesis is not considered very useful. (Perneger TV. What's wrong with Bonferroni adjustments. BMJ. 1998;316(7139):1236-1238. doi:10.1136/bmj.316.7139.1236). In addition, we have reported the exact calculated p-value, and the low p-value demonstrated for several data (0.001) is unlikely to be affected by the Bonferroni correction. However, when performing the analysis using the Bonferroni correction, the difference between COVID -19 and non COVID -19 patients in terms of HRCT scores p-value is still statistically significant, with p-value < 0.05

minor concerns)

1) In Figures 1, 2, 4, 5, and 6, the term "HRCT" was mistakenly used instead of "HRTC". Please correct appropriately.

Reply: Thank you again. All typos have been corrected.

2) In table 1, "fibrinogeno" may be mistaken for "fibrinogen" and "Ferritine" for "Ferritin". Please correct appropriately.

Reply: Amended

3) In line 228, "odd ratios" seems to be a mistake for "odds ratio". Please correct appropriately.

Reply: Amended