The Influence of the COVID-19 Pandemic on Mortality of Patients Hospitalized in Surgical Services in Romania: A Cross-Sectional Study of a National Survey

Round 1

Reviewer 1 Report

Title: The influence of the COVID-19 pandemic on mortality of patients hospitalized in surgical services in Romania: a cross-sectional study of a national survey

General comment

The underlying manuscript compared postoperative mortality in Romanian hospitals with COVID-19 positive patients and non-infected patients.

I found the manuscript is well developed with very interesting constructs to be attested.

Suggestions:

1.      The purpose of the research should be addressed in more detail. What are the differences based on previous studies? What is major theories in this study?

2.      In conducting this study, there is no review of previous studies that should be reviewed basically, such as surgical practice and characteristics of Romanian hospitals?

3.      There is very little explanation about the hypothesis set. Hypotheses are minimally developed. They should each build on clear logic and theory for each hypothesized relationship, and should relate directly to the measures that are used to represent each construct.

4.      In the conclusion part, not only academic and practical implications should be presented, but the overall conclusion of this study should be presented, including discussion of results is limited and future study.

 

I hope the suggestions above help in that process and I wish the authors well in their efforts.

Author Response

• Reviewer’s comment

1. The purpose of the research should be addressed in more detail. What are the differences based on previous studies? What is major theories in this study?

• Response
• Previous studies regarding the surgical activity in Romanian hospitals or the performances achieved during the pandemic period could not be identified.

We have made the appropriate changes, as you suggested, based on your valuable comment throughout the text.

Based on the main lines of research identified in the literature review, we have formulated the following research hypotheses:

Hypothesis 1 (H1).

Surgical activity during the pandemic decreased in Romanian hospitals in the period March-August 2022.

 

Hypothesis 2 (H2).

COVID-19 support hospitals had a lower surgical activity, compared to non COVID hospitals

 

Hypothesis 3 (H3).

The rate of emergency surgery was higher in the COVID support hospitals compared to those non COVID.

 

Hypothesis 4 (H4).

The lack of PCR test results at the time of surgery has led to the treatment of a large number of false positive patients, especially in non-Covid centers.

 

Hypothesis 5 (H5).

There was a small proportion of positive patients treated in the non COVID centers, significantly different from the one in the centers designated for the treatment of these patients.

Hypothesis 6 (H6).

The mortality rate for patients hospitalized in surgery wards during March-August 2022 was higher than in the similar period of 2021

 

Hypothesis 7 (H7).

COVID-19 support hospitals had a higher postoperative mortality, compared to non COVID-19 hospitals.

 

Hypothesis 8 (H8).

The mortality rate in positive patients from COVID-19 support centers was higher than that of those from non-Covid support centers.

 

Hypothesis 9 (H9).

The causes of death, in positive patients, operated for surgical conditions, are related in particular to the surgical disease.

 

The major hypothesis in this study is: The pandemic in Romanian hospitals induced a decrease in surgical activity and an increase in postoperative mortality.

The purpose of the study is to compare postoperative mortality during the pandemic both with the pre-pandemic period and between different COVID-19 support hospitals and non-Covid-19. Secondarily, we evaluated mortality in positive patients from the surgical wards in hospitals with and without COVID-19 support and the causes of death.

 

 

• Reviewer’s comment

2. In conducting this study, there is no review of previous studies that should be reviewed basically, such as surgical practice and characteristics of Romanian hospitals?

• Response
• To our knowledge, there are no previous studies on surgical practice and hospital characteristics in Romania in COVID-19 pandemic period.

 

• Reviewer’s comment

3. There is very little explanation about the hypothesis set. Hypotheses are minimally developed. They should each build on clear logic and theory for each hypothesized relationship, and should relate directly to the measures that are used to represent each construct.

• Response

We have introduced in the results chapter, the analyses carried out to verify each individual hypothesis.

• Reviewer’s comment

4. In the conclusion part, not only academic and practical implications should be presented, but the overall conclusion of this study should be presented, including discussion of results is limited and future study.

• Response
• We have added in the manuscript

The obtained results largely confirmed the formulated hypotheses. The flexibility shown by the centres located in the outbreak of COVID led to very similar results of the overall mortality between COVID support {5%} and non-support {4.8%} centres. Analyzing the postoperative mortality, a significant difference was found in the support centres, especially in the operated positive patients, compared to the negative or non-operated positive ones. In our study, the causes of death in positive patients were mainly determined by the surgical condition or its complications, due to the delay in the medical act induced by the restrictions imposed by the pandemic. This study is the first to present the influence of the pandemic on the mortality of patients hospitalized in surgery wards between March and August 2020 in Romania, and, of course, the limited value of the results requires future larger studies.

Reviewer 2 Report

Please give a frank account of the strengths and weaknesses of the article. Include specific, detailed comments regarding the originality, scientific quality, relevance to the field of this journal, and presentation. Check the need for tables and figures, and the adequacy of the references.

Authors should rephrase keywords. Do not use words or terms in the title as keywords: the function of keywords is to supplement the information given in the title. Words in the title are automatically included in indexes, and keywords serve as additional pointers.

The recent and professional references should be cited such as:

The psychological properties of the Arabic BDI-II and the psychological state of the general Moroccan population during the mandatory quarantine due to the COVID-19 pandemic

I Maliki, H Elmsellem, B Hafez, A EL Moussaoui, M Reda Kachmar, ...

Caspian Journal of Environmental Sciences 19 (1), 139-150

Author Response

• Reviewer’s comment

Please give a frank account of the strengths and weaknesses of the article. Include specific, detailed comments regarding the originality, scientific quality, relevance to the field of this journal, and presentation.

Response

The originality of the article lies in the fact that it is the first to present the results of a national survey of surgical activity in Romanian hospitals in the period March-August 2020, under the conditions of the application of new rules imposed by the Ministry of Health due to the CoVID-19 pandemic, but it is possible that some hypotheses developed in this study to be debated in other recent studies.

The scientific quality is given by the results obtained through this study. These can lead to a better understanding of the COVID pandemic impact on the surgical services in Romanian hospitals, unprepared to face this challenge. The limitations are given by the type of data collection that was based on the questionnaire method.

Relevance to the field of this journal

The study of the problems, the analysis of the strategies adopted and the results obtained, during the crisis period of the COVID-19 pandemic, will lead to the development of a management plan to reduce the risk in the conditions of a similar future situation.

The presentation of the article respects the methodology of a descriptive analysis,

 

 

 

 

 

 

• Reviewer’s comment

Check the need for tables and figures, and the adequacy of the references.

Response

We have checked the need for tables and figures, we have found them useful, and the references are adequate.

• Reviewer’s comment

Authors should rephrase keywords:

 Do not use words or terms in the title as keywords: the function of keywords is to supplement the information given in the title. Words in the title are automatically included in indexes, and keywords serve as additional pointers.

Response

 

We have rephrased keywords.

Keywords: COVID-19, general surgery, postoperative mortality, COVID-19 support hospitals, COVID-19 outbreak, positive COVID-19 patient, suspected COVID-19 patient.

 

• Reviewer’s comment

The recent and professional references should be cited such as:

The psychological properties of the Arabic BDI-II and the psychological state of the general Moroccan population during the mandatory quarantine due to the COVID-19 pandemic

I Maliki, H Elmsellem, B Hafez, A EL Moussaoui, M Reda Kachmar, ...

Caspian Journal of Environmental Sciences 19 (1), 139-150

Response

Thank you for your suggestion.

We have added in the manuscript

"like other studies based on data collection by questionnaire[38];"

38. Maliki, I., Elmsellem, H., Hafez, B., EL Moussaoui, A., Reda Kachmar, M., Ouahbi, A. (2021). 'The psychological properties of the Arabic BDI-II and the psychological state of the general Moroccan population during the mandatory quarantine due to the COVID-19 pandemic',Caspian Journal of Environmental Sciences, 19(1), pp. 139-150. doi: 10.22124/cjes.2021.4504

Reviewer 3 Report

1. No new information has been added along the paper. All information on the web. Only the authors replotted the results and then discussed it.

2. Based on the title of the paper, a regression model should be discussed with its residuals. Why did not the authors apply it?

3. The normality property for data should be tested.

4. The homogeneity property should be reported for data.

5. Data scattering should be plotted to obtain the shape of data. 

6. The motivations of paper must be listed.   

7. Nonparametric plots/tests should be used to discuss the claim of the authors.

Author Response

Thank you for your review. Please check the attachment for the response to each one of the observations.

Author Response File: Author Response.pdf

Reviewer 4 Report

In my opinion the paper was clear, readable or informative and will provide a valuable source document for anyone requiring a primer to know and understand this issue.   

Overall, the article follows an appropriate structure.  

The Introduction of the study is well described.  The aim of this study is well stated and of interest.  

Research design and methods were appropriate to answer the study question.   

The description of the study population, data collection and variables observed presented adequately. Results relate appropriately to the aims of the study.  

The discussion focused appropriately on the comparison of own results with the results of other studies, with possible explanations for the presented results.    

It is pleasing to see the study's limitations honestly discussed.   

Conclusions are overall supported by the results.

      

The outcomes of this research are important and have the potential to lead to further investigations of the influence of the COVID-19 pandemic on mortality of different categories patients hospitalized in other services, and, especially,  to identify factors associated with the mortality.     

Author Response

Thank you very much for your appreciation.

Round 2

Reviewer 1 Report

As a reviewer, I take over that the revised manuscript has improved significantly both in style and substance. I also reviewed the “Response to Comments” file provided by the authors and it seems that the authors successfully responded to the reviewers’ suggestions and other comments.

 

However, regarding hypothesis development, only hypotheses were listed, but no logical basis was presented for hypothesis development. When developing hypotheses, logical support for each hypothesis (based on previous studies and/or examples) must be presented.

Author Response

Reviewer 1

As a reviewer, I take over that the revised manuscript has improved significantly both in style and substance. I also reviewed the “Response to Comments” file provided by the authors and it seems that the authors successfully responded to the reviewers’ suggestions and other comments.

 

However, regarding hypothesis development, only hypotheses were listed, but no logical basis was presented for hypothesis development. When developing hypotheses, logical support for each hypothesis (based on previous studies and/or examples) must be presented.

Taking into consideration your suggestions, we have formulated the following changes, and we have introduced in the manuscript using Track Changes:

Hypothesis 1 (H1).

Due to the pandemic, specific measures have been imposed in the health system all over the world. Data from the literature suggest that through the measures adopted in different hospitals, surgical activity was reduced in the first period of the pandemic [3-6]. Based on this aspect, I formulated the following hypothesis:

Surgical activity during the pandemic decreased in Romanian hospitals in the period March-August 2022.

Hypothesis 2 (H2).

The data from the literature suggest the recommendation that, in positive patients, the priority is the treatment of the infectious disease, and the surgical condition should be resolved later, if it is not an emergency [10]. Based on this finding, we researched the activity in the COVID-19 support hospitals and the non-COVID ones, and formulated the following hypothesis:

COVID-19 support hospitals had a lower surgical activity, compared to non COVID hospitals.

Hypothesis 3 (H3).

Taking into account the recommendations suggested by the data in the literature, about performing only emergency surgical interventions in positive patients [12-15], we formulated the following hypothesis:

The rate of emergency surgery was higher in the COVID support hospitals compared to those non COVID.

 

Hypothesis 4 (H4).

The screening of patients before surgery was one of the general recommendations [12-15], but the pandemic surprised, worldwide, a health system insufficiently prepared to face such a challenge. Thus we formulated the following hypothesis:

The lack of PCR test results at the time of surgery has led to the treatment of a large number of false positive patients, especially in non-Covid centers.

 

Hypothesis 5 (H5).

The creation of COVID support centers, according to the regulations of the Romanian Ministry of Health, led to the selective hospitalization of positive patients in these centers, but all hospitals received the recommendation to create epidemiological circuits, as in other countries [5, 17]. Once the capacity of the COVID-19 centers was exceeded, the non-support centers were obliged to take care of their own surgical patients who tested positive, even though they were included in the screening program upon admission. We formulated the following hypothesis:

There was a small proportion of positive patients treated in the non COVID centers, significantly different from the one in the centers designated for the treatment of these patients.

 

Hypothesis 6 (H6).

Data from the literature present different aspects regarding postoperative mortality, some claiming that it was increased during the pandemic [16], while others deny this aspect [17]. In order to verify this information for Romania as well, we formulated the following hypothesis, which we tried to verify:

The mortality rate for patients hospitalized in surgery wards during March-August 2022 was higher than in the similar period of 2021.

 

Hypothesis 7 (H7).

Several studies have shown that the postoperative mortality in COVID-positive patients is higher and that, as much as possible, surgery should be postponed until after the resolution of the infectious disease [10]. The support hospitals selected the positive patients on the one hand, but, on the other hand, if they were in an epidemiological outbreak, they had to provide surgical assistance to all patients in the outbreak. Taking into account these aspects, we formulated the following hypothesis:

COVID-19 support hospitals had a higher postoperative mortality, compared to non COVID-19 hospitals.

Hypothesis 8 (H8).

Data from the literature [17] suggest that postoperative mortality in positive patients may be different, depending on the reporting center. In Romania, the screening of surgical patients, in non-support centers, led to the strict admission of negative patients. The subsequent appearance of the symptoms of COVID-19, together with the positive test, allowed the initiation of treatment from the first stages of the disease, allowing for a better prognosis. Based on this observation, we issued the following hypothesis:

The mortality rate in positive patients from COVID-19 support centers was higher than that of those from non-Covid support centers.

Hypothesis 9 (H9).

Some studies suggest that, in most of the cases, the causes of postoperative death, in positive patients, are related to the complications of COVID-19. Considering that in Romania, firm recommendations were issued regarding the hospitalization and only emergency surgical treatment of COVID-19 patients, we observed that, by following these rules, the postoperative mortality was determined rather by the complications of the surgical disease, and we issued the following assumption:

The causes of death, in positive patients, operated for surgical conditions, are related in particular to the surgical disease.

Author Response File: Author Response.pdf

Reviewer 3 Report

I accept the paper in the current form.

Author Response

Thank you for your kind reply.

Best regards,

Rodica Birla

Round 3

Reviewer 1 Report

The reviewer's comments were well-reflected.

However, hypotheses are not established in one sentence. Please add any necessary hypotheses. Please refer to other previous studies.

Author Response

We have taken account of your suggestions, made modifications to all the hypotheses, and added 13 new references in the manuscript.

Hypothesis 1 (H1).

Due to the pandemic, specific measures have been imposed in the health system all over the world. In the first phase of the pandemic, evidence of overwhelmed hospital services (China, Italy) constituted the only examples of an unprecedented situation. As such, the recommendations to abandon elective surgical interventions, to reduce laborious surgical procedures[18,19], to postpone elective endoscopy, and to perform only emergency surgical interventions, aimed to preserve intensive care facilities and material resources, in order to respond to the rapid increase in new cases of COVID[20,21]. Data from the literature suggest that, through the measures adopted in different hospitals, surgical activity was reduced in the first period of the pandemic [3-6, 22], while other studies report other data [23]. Based on this aspect, we would like to check if surgical activity during the pandemic decreased in Romanian hospitals also, in the period March-August 2022.

Hypothesis 2 (H2).

Some authors have shown that operated COVID-19 positive patients present an increased risk for serious perioperative morbidity and mortality and every effort should be made to utilize nonoperative therapies or to delay surgery whenever feasible [24]. In this consensus, another data from the literature suggest the recommendation that, in positive patients, the priority is the treatment of the infectious disease, and the surgical condition should be resolved later, if it is not an emergency [10]. Taking this in consideration, we researched whether this recommendation is also taken up in Romania by evaluating the activity in the COVID-19 support hospitals and the non-COVID ones, and observed that COVID-19 support hospitals had a lower surgical activity, compared to non COVID hospitals.

Hypothesis 3 (H3).

Taking into account the recommendations suggested by the data in the literature, about performing only emergency surgical interventions in positive patients [12-15], both in benign and malignant pathology[25] we want to investigate whether in Romanian hospitals, the rate of emergency surgery was higher in the COVID support hospitals, which provided surgical care for positive patients from outside the outbreaks, but also in the hospitals in the outbreak, compared to those non COVID.

Hypothesis 4 (H4).

The screening of patients before surgery was one of the general recommendations [12-15], even in the conditions of a completely asymptomatic patient [26], but the pandemic surprised, worldwide, a health system insufficiently prepared to face such a challenge. The lack of specialized laboratories for PCR testing COVID-19 constituted a problem in the selection of patients, on the other hand data from the literature suggest that a substantial number of patients with COVID-19 are not identified until after surgery[24]. The lack of PCR test results at the time of surgery has led to the treatment of a large number of false positive patients, especially in non-Covid centers.

Hypothesis 5 (H5).

The creation of COVID support centers, according to the regulations of the Romanian Ministry of Health, led to the selective hospitalization of positive patients in these centers, but all hospitals received the recommendation to create epidemiological circuits, as in other countries [5, 17] . Once the capacity of the COVID-19 centers was exceeded, the non-support centers were obliged to take care of their own surgical patients who tested positive, even though they were included in the screening program upon admission. Other authors have also noticed that a significant number of patients can become positive postoperatively [24]. Based on this observation, we considered that, there was a small proportion of positive patients treated in the non COVID centers, significantly different from the one in the centers designated for the treatment of these patients and want to verify this hypothesis.

 

Hypothesis 6 (H6).

Data from the literature present different aspects regarding postoperative mortality, the vast majority showing that it was increased during the pandemic, between 4.5 and 16% [16,24,28], while others deny this aspect [17]. A comparative study showed that for similar operations during the same time period and after adjusting for other perioperative risk factors, those with COVID-19 had higher morbidity and mortality.[24] A series of 34 patients from China with occult COVID-19 infections at the time of surgery reported dismal outcomes including development of pneumonia in all patients, ARDS in 32%, shock in 29% and a perioperative mortality rate of 21%.[27] Another study showed that on a cohort of COVID-19 positive patients, 58% experienced serious complications and the perioperative mortality rate was 17%.[24] In order to verify this information for Romania as well, we tried to conclude that the mortality rate for patients hospitalized in surgery wards during March-August 2022 was higher than in the similar period of 2021.

Hypothesis 7 (H7).

Several studies have shown that the postoperative mortality in COVID-positive patients is higher and that, as much as possible, surgery should be postponed until after the resolution of the infectious disease [10]. One prospective study showed that after 7 weeks, the postoperative mortality goes down to normal values [28]. Surgery appears to exacerbate the course of the disease of COVID-19. Severe or critical illness associated with COVID-19 was identified in 19% of patients in one study, with a mortality rate of 49% in critical cases[29]. The vast majority of previous reports found that most cases of COVID- 19 [26] lead to a mild form. A number of factors, including the physiological stress of surgery, the need for mechanical ventilation and the increased risk of other infections could theoretically exacerbate the course of COVD-19 in patients undergoing surgery. The support hospitals selected the positive patients on the one hand, but, on the other hand, if they were in an epidemiological outbreak, they had to provide surgical assistance to all patients in the outbreak. Because the patients treated during the pandemic had a combined pathology, both infectious and surgical, we suspected that COVID-19 support hospitals had a higher postoperative mortality, compared to non COVID-19 hospitals and we wanted to verify this hypothesis.

Hypothesis 8 (H8).

Data from the literature [17] suggest that postoperative mortality in positive patients may be different, depending on the reporting center. One study made a comparison between private, university and usual hospitals [30]. Also, almost half of the patients were identified as COVID positive, after the admission in the hospital [24]. In Romania, the screening of surgical patients, in non-support centers, led to the strict admission of negative patients. The subsequent appearance of the symptoms of COVID-19, together with the positive test, allowed the initiation of treatment from the first stages of the disease, allowing for a better prognosis. Based on this observation, I suspected that The mortality rate in positive patients from COVID-19 support centers was higher than that of those from non-Covid support centers.

Hypothesis 9 (H9).

Some studies suggest that, in most of the cases, the causes of postoperative death, in positive patients, are related to the complications of COVID-19, although this was hard to differentiate [31]. A study highlighted that Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19 [24]. Considering that in Romania, firm recommendations were issued regarding the hospitalization and only emergency surgical treatment of COVID-19 patients, we observed that, by following these rules, the postoperative mortality was determined rather by the complications of the surgical disease, and we wanted to we check if the causes of death, in positive patients, operated for surgical conditions, are related in particular to the surgical disease.

Reference:

18.Prachand, V.N.; Milner, R,; Angelos, P.; Posner, M.C.; Fung, J.J.; Agrawal, N.; Jeevanandam, V.; Matthews, J.B. Medically Necessary, Time-Sensitive Procedures: Scoring System to Ethically and Efficiently Manage Resource Scarcity and Provider Risk During the COVID-19 Pandemic. J Am Coll Surg. 2020;231(2):281-288. doi:10.1016/j.jamcollsurg.2020.04.011.

19. American College of Surgeons, author. COVID 19: Elective Case Triage Guidelines for Surgical Care. Am Coll Surg. 2020:24. 

20.https://www.facs.org/for-medical-professionals/covid-19/clinical-guidance/elective-case/ accessed 15 December 2022

21. Ademuyiwa, A.O.; Bekele, A.; Berhea, A.B.; Borgstein, E.; Capo-Chichi, N.; Derbew, M.; Evans, F,M.; Feyssa, M,D.; Galukande, M.; Gawande, A.A.; Gueye, S,M.; Harrison, E,; Jani, P.; Kaseje, N.; Litswa, L.; Mammo, T.N.; Mellin-Olsen, J.; Muguti, G.; Nabukenya, M.T.; Ngoga, E.; Ntirenganya, F.; Rulisa, S.; Starr, N.; Tabiri, S.; Tadesse, M.; Walker, I.; Weiser, T.G.; Wren, S.M. COVID-19 preparedness within the surgical, obstetric, and anesthetic ecosystem in subSaharan Africa. Ann Surg. 2020;272:e9–e13. 
22. Ademe, Y.; Genetu, A.; Laeke, T.; Taye, M.; Bekele, A. Impact of COVID-19 on Surgical Volume: Single-Center Experience from Addis Ababa, Ethiopia. Ethiop J Health Sci. 2022 Jan;32(1):37-44. doi: 10.4314/ejhs.v32i1.5.
23. Foo, F.J.; Ho, L.M.L.; Tan, W.J.; Koh, F.H.; Sivarajah, S.S.; Park, S.Y.; Chen, W.T.; Chew, M.H. Colorectal cancer surgery in Asia during the COVID-19 pandemic: A tale of 3 cities. Asian J Surg. 2022 May;45(5):1095-1100.
24. Knisely, A.; Zhou, Z.N.; Wu, J.; Huang, Y.; Holcomb, K.; Melamed, A.; Advincula, A.P.; Lalwani, A.; Khoury-Collado, F.; Tergas, A.I.; St. Clair, C.M.; Hou, J.Y.; Hershman, D.L.; D'Alton, M.E.; Huang, Y.Y.; Wright, J.D. Perioperative Morbidity and Mortality of Patients With COVID-19 Who Undergo Urgent and Emergent Surgical Procedures. Ann Surg. 2021 Jan 1;273(1):34-40. 
25. Surg Am Coll., editor. March 24 O, 2020 COVID-19 guidelines for triage of colorectal cancer patients.2020. https://www.facs.org/covid-19/clinical-guidance/elective-case/colorectal-cancer Accessed 15 December. [Google Scholar]
26. Zheng, M.H.; Boni, L.; Fingerhut, A. Minimally Invasive Surgery and the Novel Coronavirus Outbreak: Lessons Learned in China and Italy. Ann Surg. 2020 Jul;272(1):e5-e6. 
27. Lei, S.; Jiang, F.; Su, W.; Chen, C.; Chen, J.; Mei, W.; Zhan, L.Y.; Jia, Y.; Zhang, L.; Liu, D.; Xia, Z.Y.; Xia, Z. Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. EClinical Medicine. 2020 Apr 5;21:100331.
28. COVID Surg Collaborative, Global Surg Collaborative (2021), Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. Anesthesia, 76: 748-758. https://doi.org/10.1111/anae.15458,
29. Wu ,Z.; McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA2020; 323:1239–1242.

30.Haffner MR, Le HV, Saiz AM, et al. Postoperative In-Hospital Morbidity and Mortality of Patients With COVID-19 Infection Compared With Patients Without COVID-19 Infection. JAMA Netw Open. 2021;4(4):e215697. doi:10.1001/jamanetworkopen.2021.5697