Factors Associated with Mortality in Patients with COVID-19 from a Hospital in Northern Peru

Round 1

Reviewer 1 Report

 

Dear Editor,

I thoroughly reviewed the manuscript entitled “Factors associated with mortality in patients with COVID-19 from a hospital in northern Peru” by Vasquez-Elera et al.  The topic is important and was addressed by many large studies and several systematic reviews, which are not mentioned in the manuscript. In our opinion, the current study does not add relevant information to the current level of knowledge. Another major issue is self-citation: the first paragraph of the manuscript has fifty references, among which twenty eight are self-citations, with no significant relation with the objective of the study.

Author Response

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Reviewer 2 Report

This paper tackles an interesting question on predictors of mortality in patients with COVID-19.

I have several comments:

1.   Statistical analysis, please described more precisely how the multivariable model were performed? Any methods of selection variables”

2.     Line 89-90, How many patients were excluded? Please described more precisely, how the final sample size was obtained.

3.     Please conform that the patients with BMI<18.5 were excluded form “Normal” category.

4.     Table 1, please add the range for “Age (categorized)”.

5.     Lone 96-97, “referral or transfer to another health institution” how these patients were treated in analysis? As “discharge”? The results could be bias.

6.     Line 273-274, why these predictors were not included in the analysis?

Author Response

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Reviewer 3 Report

here are a few other comments I’d like the authors to consider so the paper can be improved:

1. Abstract needs details about the contribution statement. 

2 The authors provide a good background and literature review sections, a detailed explanation of their proposal, and compare it against related mechanisms

3. Risk factors for mortality due to COVID-19. Some charts may be included to justify the selected parameters of the study 

4. The "Conclusion"  should provide additional details about the benefits of the contribution; what are the implications for practitioners? I also recommend adding a brief discussion about future research that could advance the work done so far.

Author Response

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Round 2

Reviewer 1 Report

 

I reviewed the revised version of the manuscript entitled “Factors associated with mortality in patients with COVID-19 from a hospital in northern Peru” by Vasquez-Elera et al.  Although the current version is improved compared to the previous one, major issues which significantly impair the value of the manuscript are still present.

1.       With very few exceptions none of the large studies or systematic reviews which addressed the topic are mentioned in the manuscript. In my opinion, the current study does not add relevant information to the current level of knowledge.

 

2.       Another major issue is related to references.

The manuscript has forty-eight references, twenty of which (5-8, 12-16, 18, 25-28, 30, 31, 36, 37, 42, 44) are not related to the topic of the study (i.e., factors associated with mortality in patients with COVID-19), but to mental health. The reason why these publications are used as references is not clear. Also, some of the cited references are not related to the statements existing in the text. Please find below some examples.

 

lines 52-53 “In December 2019, the first cases of COVID-19 were reported in the city of Wuhan-China [1].” Many publications could be used as references for this well-known information but not reference 1 [Rondón, M.B. Salud mental: un problema de salud pública en el Perú. Revista Peruana de Medicina Experimental y Salud Publica 2006] which is by no means related to the above-mentioned information.

lines 53-54 “Peru was the country in South America with the highest mortality rate at 118.6 deaths per 100,000 inhabitants [2]”. This statement is not present in reference 2, where one may find “Ecuador takes the lead, presenting so far, a mortality rate of 2 per 100 thousand inhabitants, followed by Peru with 0.7 per 100 thousand inhabitants”.

lines 54-55 “the COVID-19 associated mortality in the Piura region of Peru was 5.18% of patients [3].” This statement is not present in reference 3, which describes the Timeline of COVID-19.

lines 55-58 “Regardless of the social distancing [4] and quarantines [5] measures that were implemented in Peru, the mortality [2] and mental distress [6] were considerable.” This statement might be made clearer and more specific. Several studies demonstrated the role of social distancing and quarantine in reducing viral transmission and consequently the number of COVID cases. COVID-19 mortality is influenced by many factors, including but not limited to the number of COVID-19 cases.  References 5 and 6 are not adequately used: reference 5 [Hwang, T.-J.; Rabheru, K.; Peisah, C.; Reichman, W.; Ikeda, M. Loneliness and social isolation during the COVID-19 pandemic. International psychogeriatrics 2020] describes the effects of social isolation on mental health and reference 6 [Xiao, X.; Zhu, X.; Fu, S.; Hu, Y.; Li, X.; Xiao, J. Psychological impact of healthcare workers in China during COVID-19 pneumonia epidemic: A multi-center cross-sectional survey investigation. Journal of affective disorders 2020] is a cross-sectional study from China and is not related to Peru. Reference 2 is based on data collected until April 2020. Newer references might be more useful to evaluate the effect of social distancing on mortality.

lines 58-61 “Peru has a fragile healthcare system aggravated by limited organizational support in healthcare facilities [7].” Is reference 7, a self-citation, the most adequate study to demonstrate this general statement? [Yáñez, J.A.; Jahanshahi, A.A.; Alvarez-Risco, A.; Li, J.; Zhang, S.X. Anxiety, distress, and turnover intention of healthcare workers in Peru by their distance to the epicenter during the COVID-19 crisis. American Journal of Tropical Medicine and Hygiene 2020, 103, 1614-1620,]

lines 61-67 “Furthermore, technostress related to mental distress [8] became evident and the population implemented self-care behaviors such as the use of medicinal plants [9] in a country that consumes multiple plants for medicinal purposes based on their bioactive substances content [10,11].” In my opinion references 10 and 11, which are self-citations, are at most marginally related to the statement. References 10 [Roupe, K.A.; Helms, G.L.; Halls, S.C.; Yanez, J.A.; Davies, N.M. Preparative enzymatic synthesis and HPLC analysis of rhapontigenin: applications to metabolism, pharmacokinetics and anti-cancer studies. J Pharm Pharm Sci 2005] Reference 11 [Yáñez, J.A.; Remsberg, C.M.; Takemoto, J.K.; Vega-Villa, K.R.; Andrews, P.K.; Sayre, C.L.; Martinez, S.E.; Davies, N.M. Polyphenols and Flavonoids: An Overview. In Flavonoid Pharmacokinetics: Methods of Analysis, Preclinical and Clinical Pharmacokinetics, Safety, and Toxicology, Davies, N.M., Yáñez, J.A., Eds.; John Wiley & Sons: Hoboken, NJ USA, 2012]

lines 73-79 “Studies have determined that male sex, older age [12], and presenting diabetes, hypertension, and chronic kidney disease are associated with greater severity of illness and mortality from COVID-19 [13,14]. In Peru, it was found that oxygen saturation was decreased to 87% at hospital admission in elderly patients with COVID-19 [15]. Additionally, patients with a history of hypertension, diabetes mellitus, and obesity were also associated with a higher risk of mortality from COVID-19 [15,16].” References 12-16 are related to mental health only and not to the above-mentioned statements.

lines 84-86 “Among them, it has been shown that demographic, patient history, physical examination, laboratory, and radiological factors, as well as a high SOFA score contribute importantly to deaths [18].” Again Reference 18 is related to mental health only.  Pereyra-Elías, R.; Ocampo-Mascaró, J.; Silva-Salazar, V.; Vélez-Segovia, E.; da Costa-Bullón, A.D.; Toro-Polo, L.M.; Vicuña-Ortega, J. Prevalencia y factores asociados con síntomas depresivos en estudiantes de ciencias  de la salud de una Universidad privada de Lima, Perú 2010. Revista Peruana de Medicina Experimental y Salud Publica 2010]

lines 88-91 “…but also obesity, hypertension, cardiovascular disease, cancer, and age has important influence on fatal outcomes [20]. There has also been research on specific populations; for example, deaths among older people have been related to dementia, diabetes, chronic kidney disease, and hypertension [3]” Reference 20 [UN. Chronology of the coronavirus pandemic and the actions of the World Health Organization] is similar to reference 3 [WHO Timeline - COVID-19] and none of them is even marginally related to the statements from the text.

lines 91-97 “There were even systematic reviews on specific regions of the world remarking their proper risk factors such as Europe (88 cohort studies, 6 653 207 patients, risk factors: solid organ tumors, diabetes, renal disease, arrhythmia, ischemic heart disease, and liver disease) [21] and sub-Saharan Africa (12 studies, 43598 patients, mortality 4.8%, risk factors: advanced age, male sex, chronic kidney disease, hypertension, severe or critical condition on admission, cough, and dyspnea) [21].” These data are not from reference 21.

lines 242-244 “The lethality from COVID-19 in our study was 41.3%, parallels and is similar to a seminal investigation carried out in Wuhan, China, in which 43% of patients died from SARS-CoV-2 infection [23]”. These data are not from reference 23 [Petrova, D.; Salamanca-Fernández, E.; Rodríguez Barranco, M.; Navarro Pérez, P.; Jiménez Moleón, J.J.; Sánchez, M.-J. La obesidad como factor de riesgo en personas con COVID-19: posibles mecanismos e implicaciones. Aten Primaria 2020]

line 246 “… and Fumagalli et al. (23.2%) (23.2%) [21].” These data are not from reference 21

lines 246-249 “At the regional and local level, our findings represents one of the highest fatality rates reported in the literature, and is in contrast to what has been estimated in Puebla, Mexico (35%), Santiago, Chile (27.4%), and Lima, Peru (29.4 %) [25-27].” References 25-27 are related to mental health only.

lines 249-251 “Peru had 194,935 deaths in 2020 from COVID-19, which ranked in the first place of mortality per million inhabitants at the regional and global level [28].” These data are not from reference 28 [CDC. Grief and Loss.]

lines 252-256 “The high mortality found in this research could be due in part to the insufficient amount of human and material resources available for hospital care, such as the low availability of oxygen, intensive care unit (ICU) beds (2 ICU beds per hundred thousand inhabitants), lack of personal protective equipment (PPE) and molecular tests [29-31].” References 30 and 31 are not related to these statements.

lines 259-262 “… being an older adult (over 60 years of age) increases the risk of dying from COVID-19 by 69% .... However, it differs from the risk of mortality from COVID-19 which was not significantly associated with age [35].” Could you please explain the difference between dying from COVID and mortality from COVID?

lines 261-262 “… the risk of mortality from COVID-19 which was not significantly associated with age [35].” This statement cannot be sustained by reference 35 [Sunjaya, A.P.; Allida, S.M.; Di Tanna, G.L.; Jenkins, C. Asthma and risk of infection, hospitalization, ICU admission and mortality from COVID-19: Systematic review and meta-analysis. Journal of Asthma 2022].

lines 262-266 “The vulnerability of our patients could explain this association to COVID-19, which is strictly dependent on biological age and related to other age-related diseases, characterized by the hyperfunction response of inflammatory cells to infection, which can trigger the cytokine storm hypercoagulation, lung, and distant organ damage [36-39]”. References 36 and 37 are not related to the statement. Reference 36 [Hopwood, P.; Stephens, R.J.; Party, B.M.R.C.L.C.W. Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data. Journal of Clinical Oncology 2000] Reference 37 [Natale, P.; Palmer, S.C.; Ruospo, M.; Saglimbene, V.M.; Rabindranath, K.S.; Strippoli, G.F.M. Psychosocial interventions for preventing and treating depression in dialysis patients. Cochrane Database of Systematic Reviews 2019].

lines 271-272 “…the scarce rationing of resources in saturated ICUs, the lack of an adequate number of ICU beds, and an insufficient response capacity [44].” Reference 44 [Vicente, B.; Saldivia, S.; Pihán, R. Prevalencias y brechas hoy: salud mental mañana. Acta bioethica 2016] is not useful.

lines 290-291 “This is consistent with the findings of Lee et al. who found that having altered mental status increased the risk of dying by 5.4 times [46-48].” None of the references includes Lee et al.

lines 292-295 “…the invasion of the brainstem by the virus through the angiotensin-converting enzyme 2 receptors, which facilitates the alteration at the level of the ascending reticular activation system (SARA) [12,13].” Reference 13 is not related to SARS-CoV-2 infection but to mental health [Arrieta Vergara, K.M.; Díaz Cárdenas, S.; González Martínez, F. Síntomas de depresión y ansiedad en jóvenes universitarios: prevalencia y factores relacionados. Revista Clínica de Medicina de Familia 2014].

lines 297-299 “An investigation found that having a platelet count < 125 × 297
109/L can increase the probability of death from COVID-19 by 60% [18].” Again, reference 18 is by no means related to COVID-19 [Pereyra-Elías, R.; Ocampo-Mascaró, J.; Silva-Salazar, V.; Vélez-Segovia, E.; da Costa-Bullón, A.D.; Toro-Polo, L.M.; Vicuña-Ortega, J. Prevalencia y factores asociados con síntomas depresivos en estudiantes de ciencias de la salud de una Universidad privada de Lima, Perú 2010. Revista Peruana de Medicina Experimental y Salud Publica 2010,]

Author Response

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Round 3

Reviewer 1 Report

The second revision significantly improved the quality of the manuscript entitled “Factors associated with mortality in patients with COVID-19 from a hospital in northern Peru” by Vasquez-Elera et al.  

Minor issues

1.       lines 99-100 “In Peru, it was found that oxygen saturation was decreased to 87% at hospital admission in elderly patients with COVID-19 [14]. “ In my opinion this sentence might be improved. The main conclusion from reference 14 is “among patients with COVID-19 who were admitted to a public hospital in Peru, in-hospital mortality was high and was independently associated with oxygen saturation below 90% on admission and with age over 60 years.”

2.       lines 272 – 273 “a seminal investigation carried out in Wuhan, China … [27].” Reference 27 is a retrospective cohort study from New York City, not from Wuhan, China.

 

 Sincerely yours,

Author Response

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