Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Features of patients that died for COVID-19 in a hospital in the south of Mexico: A observational cohort study

  • Jesús Arturo Ruíz-Quiñonez ,

    Contributed equally to this work with: Jesús Arturo Ruíz-Quiñonez, Crystell Guadalupe Guzmán-Priego

    Roles Conceptualization, Project administration

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Crystell Guadalupe Guzmán-Priego ,

    Contributed equally to this work with: Jesús Arturo Ruíz-Quiñonez, Crystell Guadalupe Guzmán-Priego

    Roles Data curation, Supervision

    Affiliation División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, México

  • Germán Alberto Nolasco-Rosales,

    Roles Writing – original draft, Writing – review & editing

    Affiliation División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, México

  • Carlos Alfonso Tovilla-Zarate,

    Roles Formal analysis, Software, Writing – review & editing

    Affiliation División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Tabasco, México

  • Oscar Israel Flores-Barrientos,

    Roles Investigation, Project administration, Resources

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Víctor Narváez-Osorio,

    Roles Project administration, Resources

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Guadalupe del Carmen Baeza-Flores,

    Roles Data curation, Visualization

    Affiliation División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, México

  • Thelma Beatriz Gonzalez-Castro,

    Roles Writing – original draft

    Affiliation División Académica de Multidisciplinaria de Jalpa de Méndez, Universidad Juárez Autónoma de Tabasco, Jalpa de Méndez, Tabasco, México

  • Carlos Ramón López-Brito,

    Roles Methodology, Supervision, Visualization

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Carlos Alberto Denis-García,

    Roles Supervision, Validation

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Agustín Pérez-García,

    Roles Investigation, Supervision

    Affiliation Secretaría de Salud, Hospital de Alta Especialidad Dr. Juan Graham Casasús, Villahermosa, Tabasco, México

  • Isela Esther Juárez-Rojop

    Roles Writing – review & editing

    iselajuarezrojop@hotmail.com

    Affiliation División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, México

Features of patients that died for COVID-19 in a hospital in the south of Mexico: A observational cohort study

  • Jesús Arturo Ruíz-Quiñonez, 
  • Crystell Guadalupe Guzmán-Priego, 
  • Germán Alberto Nolasco-Rosales, 
  • Carlos Alfonso Tovilla-Zarate, 
  • Oscar Israel Flores-Barrientos, 
  • Víctor Narváez-Osorio, 
  • Guadalupe del Carmen Baeza-Flores, 
  • Thelma Beatriz Gonzalez-Castro, 
  • Carlos Ramón López-Brito, 
  • Carlos Alberto Denis-García
PLOS
x

Abstract

Background

Due to the wide spread of SARS-CoV2 around the world, the risk of death in individuals with metabolic comorbidities has dangerously increased. Mexico has a high number of infected individuals and deaths by COVID-19 as well as an important burden of metabolic diseases; nevertheless, reports about features of Mexican individuals with COVID-19 are scarce. The aim of this study was to evaluate demographic features, clinical characteristics and the pharmacological treatment of individuals who died by COVID-19 in the south of Mexico.

Methods

We performed an observational study including the information of 185 deceased individuals with confirmed diagnoses of COVID-19. Data were retrieved from medical records. Categorical data were expressed as proportions (%) and numerical data were expressed as mean ± standard deviation. Comorbidities and overlapping symptoms were plotted as Venn diagrams. Drug clusters were plotted as dendrograms.

Results

The mean age was 59.53 years. There was a male predominance (60.1%). The mean hospital stay was 4.75 ± 4.43 days. The most frequent symptoms were dyspnea (88.77%), fever (71.42%) and dry cough (64.28%). Present comorbidities included diabetes (60.63%), hypertension (59.57%) and obesity (43.61%). The main drugs used for treating COVID-19 were azithromycin (60.6%), hydroxychloroquine (53.0%) and oseltamivir (27.3%).

Conclusions

Mexican individuals who died of COVID-19 had shorter hospital stays, higher frequency of shortness of breath, and higher prevalence of diabetes than individuals from other countries. Also, there was a high frequency of off-label use of drugs for their treatment.

Introduction

On December 31, 2019, the World Health Organization (WHO) was informed of cases of pneumonia of unknown etiology in Wuhan, China. The Chinese authorities identified a new type of coronavirus, which was isolated on January 7, 2020 [1]. Coronaviruses are enveloped RNA viruses, which are the cause of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) in humans. The novel coronavirus was named SARS-CoV2 and COVID-19 is the name of the disease [2, 3]. Since it was discovered, SARS-CoV-2 has widely spread around the world; by August 15th 2020, there were 21,037,564 confirmed cases and 755,455 deaths reported worldwide [4].

To date, there are some reports and reviews about the characteristics of those who have had COVID-19 in a few populations around the world. These reports agree that the median age in individuals who were hospitalized due to COVID-19 was between 47 and 73 years, with a male predominance (60%). Also, the most common symptoms were fever (90%), dry cough (60–86%), shortness of breath (53–80%), fatigue (38%), nausea/vomiting or diarrhea (15–39%), and myalgia (15–44%). The most frequent comorbidities observed included hypertension (48–57%), diabetes (17–34%) and cardiovascular diseases (21–28%). They also reported that comorbidities were more common in hospitalized individuals (60–90%) compared with the overall population infected by COVID-19 (25%) [5].

In Mexico, the first case of COVID-19 was detected on February 27, 2020 [6]; by August 15th, there were 505,751 confirmed cases and 55,293 deaths [4]. Because there is an important burden of metabolic diseases such as diabetes (10.3%), hypertension (18.4%) and obesity (36.1%) in the Mexican population [7], this population could be highly vulnerable to COVID-19.

Up to today, there are very few reports in the Mexican population that have used epidemiological data to evaluate comorbidities as risk factors of COVID-19 [8, 9]. For instance, we found only one report that evaluated gastrointestinal symptoms in Mexican individuals with COVID-19 [10].

We consider that is also important to evaluate the pharmacological treatment most commonly used in Mexico to treat COVID-19. Although there is not directed antiviral therapy recommended against SARS-CoV-2 [1113], it is common knowledge that Mexican hospital include the use of antivirals for the treatment of individuals with COVID-19. Therefore, our aim was to evaluate demographic features, clinical characteristics, and pharmacological treatment received by individuals who died by COVID-19 in a third level hospital in the south of Mexico.

Methods

This was an observational retrospective study performed at the High-Specialty Regional Hospital “Dr. Juan Graham Casasús” (HJGC) in Villahermosa, Tabasco, Mexico. We used the medical records of every individual who died by COVID-19 and was admitted to hospital (HJGC) from April 15th to May 12th, 2020. These individuals were diagnosed with COVID-19 by epidemiologists following the Mexican Health Secretary’s guidelines; additionally, they tested positive for SARS-CoV-2 by Reverse Transcriptase Polymerase Chain Reaction. The ethical approval was granted by the Research Ethics Committee of the Juarez Autonomous University of Tabasco (103/CIP-DACS/2020) in Mexico, and ethics committee of HJGC waived the requirement for informed consent.

Three physician doctors retrieved data from clinical files after patients’ death. Data collected included age, gender, clinical symptoms, underlying comorbidities, length of hospital stay, and drugs used for the treatment of COVID-19.

We performed a descriptive report. Numerical data were expressed as mean ± standard deviation; categorical data were expressed as proportions (%). The distribution of gender, age and comorbidities were compared using the Chi-squared test, with significance of p = 0.05. Comorbidities and overlapping symptoms where plotted as Venn diagrams. Drug clusters were plotted as dendrograms. All data were analyzed using SPSS v.23.

Results

We selected the files of 185 deceased individuals who had COVID-19; these individuals had been diagnosed and treated for COVID-19 between April 15 and May 12, 2020 at the HJGC in Villahermosa Tabasco, Mexico. The length of time hospitalized was 4.75 days in means (S.D. 4.43). The distribution of days of hospitalization by gender is shown in Fig 1. All patients included in this study died of cardiorespiratory arrest, secondary to acute respiratory failure.

thumbnail
Fig 1. Individuals who died of COVID-19 stratified by gender and days of hospitalization.

https://doi.org/10.1371/journal.pone.0245394.g001

Age and gender

The mean age of the individuals studied was 59.53±12.50 (range 24–86) years. When we stratified them by age, the majority were individuals of 65+ years (36.7%, n = 58). Nevertheless, the groups of 55 and 65+ years constituted 67.7% of the sample (n = 107). The comparison between males and females is shown in Table 1. No significant differences were observed between groups in terms of age.

thumbnail
Table 1. Characteristics stratified by gender of individuals who died of COVID-19.

https://doi.org/10.1371/journal.pone.0245394.t001

Symptoms

The most common symptoms on admission were shortness of breath (88.77%), fever (71.42%), dry cough (64.28%), headache (43.87%) and myalgia (34.69%). Frequencies per gender are shown in Table 2. When overlapping symptoms were observed, the first cluster included fever, dry cough, shortness of breath and headache. Another cluster included fever, dry cough, shortness of breath, myalgia, arthralgia, and headache. Then fever, dry cough, shortness of breath, myalgia, and arthralgia without headache. And fever and shortness of breath (Fig 2).

thumbnail
Fig 2. Venn diagram of overlapping symptoms.

We plotted overlaps between the three main symptoms reported in the sample. The higher proportions were fever or cough only, without manifestation of another symptom. The largest overlap was the triad fever-cough-dyspnea. Then, in order of frequency the main overlaps were fever-dyspnea and cough-dyspnea.

https://doi.org/10.1371/journal.pone.0245394.g002

thumbnail
Table 2. Symptoms frequencies stratified by gender of individuals who died of COVID-19.

https://doi.org/10.1371/journal.pone.0245394.t002

Comorbidities

The most common comorbidities on admission were Type 2 Diabetes (60.63%), hypertension (59.57%) and obesity (43.61%) (Table 1). The main overlap between these comorbidities were T2D-Hypertensión. The second overlap was T2DM-Hypertension-Obesity and finally Hypertension-Obesity (Fig 3). Other less frequent comorbidities observed in individuals who died by COVID-19 are depicted in Table 3. There was one individual with HIV and other two with cancer; the three of them were immunosuppressed. It is important to mention that these individuals were also receiving the usual treatment for their underlying disease while they were treated in hospital for COVID-19.

thumbnail
Fig 3. Venn diagram of overlapping comorbidities.

The main overlap was the dyad Hypertension-T2D. The frequency of these comorbidities alone was almost equal. The next overlaps in order of frequency were the triad Hypertension-T2D-Obesity and the dyad Hypertension-Obesity.

https://doi.org/10.1371/journal.pone.0245394.g003

Pharmacological therapy

The most frequent drugs used for treating individuals with COVID-19 were azithromycin (69.32%) and hydroxychloroquine (61.36%). Less frequently employed were oseltamivir (38.64%), lopinavir-ritonavir (26.14%) and tocilizumab (22.73%). Drugs for various purposes (e.g. paracetamol, dexamethasone, enoxaparin) were grouped as others, these were given to 73.86% of the patients (Table 4).

We observed that azithromycin and hydroxychloroquine were frequently given together, followed by lopinavir-ritonavir with tocilizumab, and oseltamivir with lopinavir-ritonavir or tocilizumab (Fig 4).

thumbnail
Fig 4. Dendrogram of relationships between drugs used.

The closest relation was azithromycin–hydroxychloroquine, followed by oseltamivir–lopinavir or tocilizumab.

https://doi.org/10.1371/journal.pone.0245394.g004

Discussion

In this study, we gathered clinical and demographic characteristics of individuals who died of COVID-19; we also identified drugs that were most frequently used as antiviral treatment in those individuals.

According to Mexico’s epidemiological data [8], there is a male predominance for COVID-19. Then, having 60% males in our sample was expected. Furthermore, this predominance is also observed in other populations including Chinese and British [5, 1416]. We found that 67.7% of individuals were ≥55 years old. Similar findings had been observed in the state of Sonora, Northwest of Mexico, with a mean age of 56.98 years old in individuals who died by COVID-19 [17]. On the other hand, reports in the USA population indicated that the majority of individuals who have died of COVID-19 were also males (53.3%), and aged ≥65 years (78.2%) [18]. Although age varied widely among reports, we consider that our results still reflect similar demographic characteristics to patients with severe COVID-19 in other populations [14, 19]. The mean length time hospitalized in days was 4.75 ± 4.43, which is shorter than what was reported in an observational study of fatal cases from Wuhan, China (6.35 ± 4.51) [19].

Shortness of breath, fever and dry cough were the most prevalent symptoms in our sample. Fever and cough had been reported as the most prevalent symptoms in case series from Europe, China, Mexico and in severe cases [5, 10, 15, 1921]. On the other hand, the third most prevalent symptom varied widely; for instance, a review found dyspnea in 53–80% of cases, while a series of fatal cases in Wuhan found dyspnea in 70.6% [5, 19]. Nonetheless, in clinical series and meta-analysis involving non-lethal cases in Asia, Europe, and North America, the third most prevalent symptom was myalgias or fatigue (31–67%) [10, 15, 20, 21]. In our sample, shortness of breath was the most prevalent symptom, and it was present in every cluster of symptoms, which could indicate that shortness of breath is an early symptom of bad prognosis.

The most common comorbidities in our sample were type 2 diabetes, hypertension, and obesity. Remarkably, diabetes and hypertension were found in similar frequencies. It has been reported that in Mexican individuals with COVID-19 there is a slightly higher frequency of hypertension than diabetes [8, 10]. Additionally, a report from Northwest Mexico indicated that diabetes and hypertension have higher risk of mortality than other comorbidities [17]. In a follow-up study of 20,133 individuals with COVID-19 in United Kingdom, the most frequent comorbidities were chronic cardiac disease (31%), uncomplicated diabetes (21%), non-asthmatic chronic pulmonary disease (18%), and chronic kidney disease (16%); while only 23% reported no major comorbidities [22]. On the other hand, a report in Northeast Brazil showed that the mortality of COVID-19 was enhanced by old age, neurological diseases, pneumopathies and cardiovascular diseases [23].

Nonetheless, hypertension has a much higher prevalence compared to diabetes in reports from USA, Italy and China [5, 20]. In two meta-analyses from the same work group [24, 25], hypertension and diabetes were associated with poor outcomes in COVID-19. The association with hypertension was influenced by gender, but not by age or diabetes, while the association with diabetes was influenced by age and hypertension. On the other hand, in a study using a UK database [16], hypertension was associated with an increased risk of COVID-19 (HR 1.09) but there was no association when the risk was adjusted to age, gender, diabetes and obesity. In addition, diabetes and obesity were associated with an increased risk of death (HR 1.90 and 1.92, respectively).

Epidemiological data of COVID-19 in Mexico, indicate that obesity is a risk factor of death and is a partial mediator on the effects of diabetes in decreased survival [8]. Finally, when comorbidities in our sample were clustered, we observed a lower frequency of individuals with only-hypertension compared with only-diabetes and only-obesity patients. Therefore, diabetes and obesity should not be overlooked as strong risk factors and poor outcomes in individuals with COVID-19.

In our sample, the most frequent pharmacological treatment was hydroxychloroquine associated with azithromycin. Although there is evidence of an in vitro activity against SARS-CoV-2, the use of hydroxychloroquine and azithromycin for clinical benefit is only supported by limited and conflicting clinical data [26]. Antiviral agents were the second most frequently used treatment; for instance, oseltamivir was the third most administrated treatment; however, there are no reports about oseltamivir having in vitro activity against SARS-CoV-2. Although some clinical trials have included oseltamivir, it is not proposed as therapeutic intervention [27]. Lopinavir-ritonavir was less frequently used as treatment in our sample; while in vitro activity against SARS-CoV-2 has been reported, clinical trials have failed in associate it with better clinical outcomes [28]. Finally, the only immunomodulatory drug used in our sample was tocilizumab. In a meta-analysis, tocilizumab was associated with a significant decrease in mortality rate and ameliorate clinical symptoms in patients with COVID-19 [29]. Despite of their promising results, immunomodulatory drugs access is limited and they are not broadly used in clinical settings in Mexico.

Our study has some limitations that need to be considered. First, we had limited information about some individuals because they died within minutes after their arrival to the emergency room. Second, we did not include surviving individuals so we could not compare characteristics between groups. Third, we included data of only one frontline hospital for treating COVID-19 that only show characteristics and handling of patients at the beginning of the COVID-19 pandemic in south Mexico; therefore, our data should not be applied to the whole Mexican population.

In conclusion, our study showed a high use of off-label of drugs that have insufficient evidence of their efficacy against COVID-19. The individuals in our sample had shorter hospital stays, higher frequency of shortness of breath, and higher prevalence of diabetes than similar populations from other countries. It is important to perform more clinical series and cohorts in Mexican population, as this population shows features that could differ of populations from other countries.

References

  1. 1. World Health Organization. Situation Report—1 [Internet]. Geneva: World Health Organization; 2020 [updated 01/20/2020; cited 2020 Jul 6]. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200121-sitrep-1-2019-ncov.pdf?sfvrsn=20a99c10_4.
  2. 2. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine. 2020;382(8):727–33.
  3. 3. World Health Organization. Naming the coronavirus disease (COVID-19) and the virus that causes it. [Internet]. Geneva: World Health Organization; 2020 [updated 2020 Feb 11; cited 2020 Jul 5]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it.
  4. 4. WHO coronavirus disease (COVID-19) dashboard. [Internet]. World Health Organization. 2020 [cited 2020 Aug 25]. https://covid19.who.int/.
  5. 5. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; pmid:32648899
  6. 6. Suárez V, Suarez Quezada M, Oros Ruiz S, Ronquillo De Jesús E. Epidemiología de COVID-19 en México: del 27 de febrero al 30 de abril de 2020. Revista Clínica Española. 2020; pmid:32560915
  7. 7. Instituto Nacional de Estadística y Geografía. Encuesta Nacional de Salud y Nutrición (ENSANUT) 2018 [Internet]. Mexico City: Instituto Nacional de Estadística y Geografía; 2018 [updated 2020 Apr 20; cited 2020 Jul 14]. https://www.inegi.org.mx/programas/ensanut/2018/default.html#Documentacion.
  8. 8. Bello-Chavolla OY, Bahena-López JP, Antonio-Villa NE, Vargas-Vázquez A, González-Díaz A, Márquez-Salinas A, et al. Predicting Mortality Due to SARS-CoV-2: A Mechanistic Score Relating Obesity and Diabetes to COVID-19 Outcomes in Mexico. The Journal of Clinical Endocrinology & Metabolism. 2020;105(8). pmid:32474598
  9. 9. Kammar-García A, Vidal-Mayo JJ, Vera-Zertuche JM, Lazcano-Hernández M, Vera-López O, Segura-Badilla O, et al. Impact of Comorbidities in Mexican SARS-CoV-2-Positive Patients: A Restrospective Analysis in a National Cohort. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2020;72(3):151–8.
  10. 10. Remes-Troche JM, Ramos-de-la-Medina A, Manríquez-Reyes M, Martínez-Pérez-Maldonado L, Lara EL, Solís-González MA. Initial Gastrointestinal Manifestations in Patients with SARS-CoV-2 in 112 patients from Veracruz (Southeastern Mexico). Gastroenterology. 2020;.
  11. 11. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Medicine. 2020;46(5):854–87. pmid:32222812
  12. 12. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines [Internet]. Bethesda: National Institutes of Health; 2020 [cited 2020 Jul 26]. https://www.covid19treatmentguidelines.nih.gov/.
  13. 13. Secretaría de Salud. Recomendaciones para el tratamiento de la infección por SARS-CoV2, agente causal de COVID-19. [Internet]. Mexico City: Secretaría de Salud; 2020 [updated 07/06/2020; cited 2020 07/26]. https://coronavirus.gob.mx/wp-content/uploads/2020/07/Recomendaciones_para_tratamiento_SARS-CoV2.pdf.
  14. 14. Yu Y, Xu D, Fu S, Zhang J, Yang X, Xu L, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study. Critical Care. 2020;24(1):219. pmid:32410714
  15. 15. Li L-q, Huang T, Wang Y-q, Wang Z-p, Liang Y, Huang T-b, et al. COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. Journal of Medical Virology. 2020;92(6):577–83. pmid:32162702
  16. 16. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020; pmid:32640463
  17. 17. Álvarez-López DI, Espinoza-Molina MP, Cruz-Loustaunau ID, Álvarez-Hernández G. [Diabetes and hypertension as factors associated with Covid-19 lethality in Sonora, Mexico, 2020]. Salud publica de Mexico. 2020;62(5):456–7. pmid:33027852
  18. 18. Gold JAW, Rossen LM, Ahmad FB, Sutton P, Li Z, Salvatore PP, et al. Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19—United States, May-August 2020. MMWR Morbidity and mortality weekly report. 2020;69(42):1517–21. pmid:33090984
  19. 19. Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. American Journal of Respiratory and Critical Care Medicine. 2020;201(11):1372–9. pmid:32242738
  20. 20. Tahvildari A, Arbabi M, Farsi Y, Jamshidi P, Hasanzadeh S, Calcagno TM, et al. Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series. Frontiers in Medicine. 2020;7:231. pmid:32574328
  21. 21. Grant MC, Geoghegan L, Arbyn M, Mohammed Z, McGuinness L, Clarke EL, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLOS ONE. 2020;15(6):e0234765. pmid:32574165
  22. 22. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ (Clinical research ed). 2020;369:m1985. pmid:32444460
  23. 23. Sousa GJB, Garces TS, Cestari VRF, Florêncio RS, Moreira TMM, Pereira MLD. Mortality and survival of COVID-19. Epidemiology and Infection. 2020;148:e123. pmid:32580809
  24. 24. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia–A systematic review, meta-analysis, and meta-regression. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(4):395–403. pmid:32334395
  25. 25. Pranata R, Lim MA, Huang I, Raharjo SB, Lukito AA. Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression. Journal of the Renin-Angiotensin-Aldosterone System. 2020;21(2):1470320320926899. pmid:32408793
  26. 26. Vijayvargiya P, Esquer Garrigos Z, Castillo Almeida NE, Gurram PR, Stevens RW, Razonable RR. Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof). Mayo Clinic Proceedings. 2020;95(7):1454–66. pmid:32561148
  27. 27. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;323(18):1824–36. pmid:32282022
  28. 28. Kotwani A, Gandra S. Potential pharmacological agents for COVID-19. Indian J Public Health. 2020;64(6):112–6. pmid:32496239
  29. 29. Talaie H, Hosseini SM, Nazari M, Fakhri Y, Mousavizadeh A, Vatanpour H, et al. Is there any potential management against COVID-19? A systematic review and meta-analysis. DARU Journal of Pharmaceutical Sciences. 2020; pmid:32812187