Secondary Complications in COVID-19 Patients: A Case Series

Round 1

Reviewer 1 Report

English editing may be required

Page 2 line 86 she tested positive for COVID19. Diagnose of pneumonia can be stroke clinical or by chest imaging.

Page 2 line 92 It is not clear the reason for total body CT scan

Page 3 line 125 It could be discussed a screening role for ultrasound

Page 4 line 172 It should be discussed the symptoms to suspect ischemic stroke 

Page 5 232 It is not clear with authors recommend it in all patients or in which case is important

Case 6 Patients with COVID19 Pneumonia usually underwent chest CT, not only in the suspect of PM

I suggest to consider the possibility to discuss all cases after their presentation. I suggest to explain the role of CT in specific clinical condition and to explain the advantages in confront of other test 

Author Response

Point 1: English editing may be required

Response 1: thank you. A native English speaker will review the text.

Point 2: Page 2 line 86 she tested positive for COVID19. Diagnose of pneumonia can be stroke clinical or by chest imaging.

Response 2:thank you for the suggestion.
The patient tested positive for the covid-19 swab, we changed the text, now the thing is clearer

Point 3: Page 2 line 92 It is not clear the reason for total body CT scan

Response 3: The sudden increase in laboratory parameters and the patient's clinic required the CT study with contrast medium

Point 4: Page 3 line 125 It could be discussed a screening role for ultrasound

Response 4: text modified, now the role for ultrasound screening is written.

Point 5 : Page 4 line 172 It should be discussed the symptoms to suspect ischemic stroke 

Response 5: text modified, now in the text stroke signs and symptoms are discussed.

Point 6: Page 5 232 It is not clear with authors recommend it in all patients or in which case is important

Response 6: you are right.A CT study with contrast medium is not necessary in all cases, now we have specified that when a hemodynamic instability with an increase in the size of the hematoma is required, it is necessary to continue with the study in question.

Point 7 : Case 6 Patients with COVID19 Pneumonia usually underwent chest CT, not only in the suspect of PM

Response 7: now we have specified the comparison with the radiographic method.

Point 8 : I suggest to consider the possibility to discuss all cases after their presentation. I suggest to explain the role of CT in specific clinical condition and to explain the advantages in confront of other test 

Response 8: the authors considered  more useful to discuss case by case, to avoid making the contribution of each individual case less incisive. This work, which recounts a consecutive case series, uses only CT, which is the prevalent and most used method in urgency and especially in covid patients.

Reviewer 2 Report

With regard to COVID-19, there are many articles reporting, especially the complications are also very reported, and we believe that there are some shortcomings in novelty. The authors showed us the diagnostic role of CT in the early diagnosis and treatment of COVID-19 complications through a case series, giving us some inspiration and also a certain supporting role for clinical work. I still hope that the authors will be able to summarize these cases and add other inflammatory markers to do multi-omics research will be more outstanding.

Author Response

Point 1:  With regard to COVID-19, there are many articles reporting, especially the complications are also very reported, and we believe that there are some shortcomings in novelty. The authors showed us the diagnostic role of CT in the early diagnosis and treatment of COVID-19 complications through a case series, giving us some inspiration and also a certain supporting role for clinical work. I still hope that the authors will be able to summarize these cases and add other inflammatory markers to do multi-omics research will be more outstanding.

Response 1: We thank you for this note, we have modified the text trying to meet your suggestions, inserting some new paragraph and enriched the bibliography, in order to make the results and conclusions clearer.

As for the laboratory data, unfortunately we cannot do better.

Reviewer 3 Report

This study described several COVID-19 patients with secondary complications. The role of CT in the early diagnosis of severe COVID-19 complications was the objective of this study. This study is timely. But there are many limitations in this manuscript.

1. First of all, the association between COVID-19 and the secondary complications in this study including renal cortical necrosis and splenic infarction, cerebral ischemic stroke, rectus hematoma, active bleeding of the right lower limb, renal hematoma, pneumomediastinum, paravertebral abscess collections are unclear. The associations between COVID-19 and respective complications should be described more.

2. In this manuscript, CT was emphasized for the early diagnosis of the complications such as thrombosis, ischemic stroke, infraction, and pneumomediastinum. However, it is necessary to verify the higher significance of CT than other imaging modalities. It is better to mention the usefulness of other imaging modalities such as MRI in specific complications (e.g. Case 2, cerebral ischemic stroke).

3. There are many mistakes in using the abbreviations. Match the abbreviations corresponding to the same terminology (e.g. COVID-19, COVID 19, Covid) with the same abbreviation. Explain the abbreviations at the first appearance, and then use the abbreviations from the second appearance.

4. The manuscript is lengthy and several sentences are duplicated. There are several misspellings (e.g. in line 315). The manuscript should be reviewed again and it had better to check the English again.

Author Response

Point 1:  First of all, the association between COVID-19 and the secondary complications in this study including renal cortical necrosis and splenic infarction, cerebral ischemic stroke, rectus hematoma, active bleeding of the right lower limb, renal hematoma, pneumomediastinum, paravertebral abscess collections are unclear. The associations between COVID-19 and respective complications should be described more.

Response 1: We thank you for this note, and we have further added where possible some paragraph where we dealt with these points and further enriched the bibliography. In addition in some cases now we have added the incidence of this complication.
As you know, it is not always easy to evaluate it, especially in complications from coagulation alterations.

Point 2: In this manuscript, CT was emphasized for the early diagnosis of the complications such as thrombosis, ischemic stroke, infraction, and pneumomediastinum. However, it is necessary to verify the higher significance of CT than other imaging modalities. It is better to mention the usefulness of other imaging modalities such as MRI in specific complications (e.g. Case 2, cerebral ischemic stroke).

Response 2: This work, which recounts a consecutive case series, uses only CT, which is the prevalent and most used method in urgency and especially in covid patients.

Our study describes the complication of ischemic stroke; it is certain that the resonance study is necessary for the differential diagnosis in those cases that include posterior reversible encephalopathy syndrome (PRES), cerebral venous thrombosis, hypoxic ischemic encephalopathy or acute hemorrhagic necrotizing encephalopathy.

It is important to consider MRI brain for accurate diagnosis in patients with unexplained neurological symptoms in COVID-19, but it’s not our case.

As explained in the article that we have now added (Prasad A, Kataria S, Srivastava S, Lakhani DA, Sriwastava S. Multiple embolic stroke on magnetic resonance imaging of the brain in a COVID-19 case with persistent encephalopathy. Clin Imaging. 2021 Jan;69:285-288. doi: 10.1016/j.clinimag.2020.09.010. Epub 2020 Oct 6. PMID: 33038618; PMCID: PMC7536517.) thanks to your note for greater clarity of the topic to the reader, the resonance has limits compared to CT scan.

“There can be several challenges in obtaining MRI brain imaging in COVID-19 patients. The biggest risk is of cross contamination to other patients and technologists. Also, MRI suite requires prolonged down time for sanitization after each scan which can delay the availability of MRI imaging for other patients. MRI brain imaging can also be labor intensive on many of the COVID-19 patients as they are critically ill on mechanical ventilation and also may be unable to tolerate lying supine for the prolonged duration of the MRI scan.”

Point 3: There are many mistakes in using the abbreviations. Match the abbreviations corresponding to the same terminology (e.g. COVID-19, COVID 19, Covid) with the same abbreviation. Explain the abbreviations at the first appearance, and then use the abbreviations from the second appearance.

Response 3: you are right.

We thank you for pointing out this inconsistency, we have standardized the text.

Point 4 :The manuscript is lengthy and several sentences are duplicated. There are several misspellings (e.g. in line 315). The manuscript should be reviewed again and it had better to check the English again.

Response 4: you are right. Thank you.
We modified the typing errors and a native Englishspeaker will review it.

Reviewer 4 Report

In this manuscript, the authors report the diagnostics role of CT in the early diagnosis and management of patients with severe Covid complications through case series. The authors conclude CT imaging modality with its high sensitivity and specificity remains the preferred imaging choice to early diagnose the different complications associated with the COVID 19 such as thrombosis, ischemic stroke, infarction, and pneumomediastinum and their management that significantly improved the outcomes.

The review is of broad and cross-disciplinary interest. The topic and content discussed in this manuscript are within the scope of the journal. The organization and subsections are also appropriate. The manuscript is structured and presented in a reader-friendly manner.

Minor comments

In figure 1, I suggest the authors should indicate what the arrows are in the figure legend. And in other figures, it is better to label the damaged area with arrows.

The English of your manuscript must be improved before resubmission

Author Response

Point 1:  In figure 1, I suggest the authors should indicate what the arrows are in the figure legend. And in other figures, it is better to label the damaged area with arrows.
The English of your manuscript must be improved before resubmission

Response 1: We thank you for this note, in the images where the arrows were present we have modified the description as you rightly suggested.

We modified the typing errors and a native Englishspeaker will review it.

Round 2

Reviewer 1 Report

I appreciated the manuscript after revision. 

Author Response

Response to Reviewer Comments Round 2

Point 1 :  Abstract: L19-24. Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily cause respiratory tract infection is not limited to respiratory distress syndrome but also implicated in other body systems. The systemic complications were reported due to exaggerated inflammatory response 
which involves severe alveolar damage in the lungs and exacerbated the hypercoagulation that  lead to venous thrombosis, ischemic attack, vascular dysfunction and infarction of visceral abdominal organs. Anticoagulant drugs are administrated to stable hypercoagulability but increase 
the risk of bleeding, hematoma and haemorrhage. Pneumomediastinum, cortical kidney necrosis, splenic infarction, cerebral ischemic stroke, thrombosis of the lower limb, and hematomas are the most major complications that will be reviewed in this study. The objective of this study is to report 
the diagnostics role of CT in the early diagnosis and management of patients with severe Covid complications through case series. The abstract is rumbling and difficult to read please divide it in different sections (e.g. Background, methods,  ..)

Response 1 : Thanks for advice, we have modified the abstract so that it is now more schematized and easier to understand, with the inclusion of an introduction, the purpose of the study, materials and methods, cases and improved conclusions

Point 2: Introduction. L33-38 Patients with COVID-19 may have a wide range of symptoms, although clinically asymptomatic cases can also be found; multiple comorbidities are linked to severe clinical symptoms such as acute respiratory distress syndrome (ARDS)[2]. The main symptoms of 
COVID-19 are headache, fever, sore throat, cough, fatigue, breathlessness. Comorbidities 
in COVID-19 patients can lead to severe clinical manifestation. please improve this paragraph and add these recent references:
a- Diagnostic Accuracy of Chest Digital Tomosynthesis in Patients Recovering after COVID-19 Pneumonia. Tomography. 2022;8(3):1221-1227. doi:10.3390/tomography8030100
b- Radiological-pathological signatures of patients with COVID-19-related pneumomediastinum: is there a role for the Sonic hedgehog and Wnt5a pathways?. ERJ Open Res. 2021;7(3):00346-2021. Published 2021 Aug 23. doi:10.1183/23120541.00346-2021

Response 2: Thanks, now we have implemented the introduction part and inserted the two references you suggest that now make the work richer. We found the part about the Sonic hedgehog and Wnt5a pathways very interesting

Point 3 :

Conclusions L452-456. As the onset of the pandemics COVID-19, CT imaging modality with its high sensitivity and specificity remains the prefered imaging choice to early diagnose the different 
complications associated with the COVID-19 such as thrombosis, ischemic stroke, infarction and pneumomediastinum and their management that significantly improved the outcomes. please underline the novelty of the article and underline the clinical implications.

Response 3:

In reviewing the work, we agree with you that the conclusions were a little meager.

Now we have implemented them in order to highlight our results and thoughts and the reason for the usefulness of our study.

Author Response File: Author Response.docx