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Oxford University Press - PMC COVID-19 Collection logoLink to Oxford University Press - PMC COVID-19 Collection
. 2021 Feb 15:dyab008. doi: 10.1093/ije/dyab008

Characterizing a two-pronged epidemic in Mexico of non-communicable diseases and SARS-Cov-2: factors associated with increased case-fatality rates

Eric Monterrubio-Flores 1, María D Ramírez-Villalobos 2,, Juan Espinosa-Montero 1, Bernardo Hernandez 3, Simón Barquera 1, Victor E Villalobos-Daniel 4, Ismael Campos-Nonato 1
PMCID: PMC7928870  PMID: 33585901

Abstract

Background

People with a previous diagnosis of non-communicable diseases (NCDs) are more likely to develop serious forms of COVID-19 or die. Mexico is the country with the fourth highest fatality rate from SARS-Cov-2, with high mortality in younger adults.

Objectives

To describe and characterize the association of NCDs with the case-fatality rate (CFR) adjusted by age and sex in Mexican adults with a positive diagnosis for SARS-Cov-2.

Methods

We studied Mexican adults aged ≥20 years who tested positive for SARS-Cov-2 during the period from 28 February to 31 July 2020. The CFR was calculated and associations with history of NCDs (number of diseases and combinations), severity indicators and type of institution that treated the patient were explored. The relative risk (RR) of death was estimated using Poisson models and CFR was adjusted using logistic models.

Results

We analysed 406 966 SARS-Cov-2-positive adults. The CFR was 11.2% (13.7% in men and 8.4% in women). The CFR was positively associated with age and number of NCDs (p trend <0.001). The number of NCDs increased the risk of death in younger adults when they presented three or more NCDs compared with those who did not have any NCDs [RR, 46.6; 95% confidence interval (CI), 28.2, 76.9 for women; RR, 16.5; 95% CI, 9.9, 27.3 for men]. Lastly, there was great heterogeneity in the CFR by institution, from 4.6% in private institutions to 18.9% in public institutions.

Conclusion

In younger adults, higher CFRs were associated with the total number of NCDs and some combinations of type 2 diabetes, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease.

Keywords: Hypertension, diabetes, cardiovascular disease, COVID-19, SARS-Cov-2, mortality


Key Messages

  • The relative risk (RR) of death increases with the number of non-communicable diseases (NCDs).

  • NCDs increase the RR of death differentially by age groups, with the highest RR seen in young adults.

  • Some combinations of NCDs are associated with greater increases in case-fatality rates (CFRs).

  • There is great heterogeneity in the CFR by type of healthcare institution.

Background

The severe acute respiratory syndrome coronavirus 2 disease (COVID-19)1 can produce mild respiratory symptoms that remit naturally.2 However, in some cases, it can also evolve into acute respiratory distress syndrome, causing multiple-organ failure and death.3

As of 8 November 2020, >50.3 million people have been infected with SARS-Cov-2 worldwide and >1.254 million have died from this cause. When comparing the mortality rate per 100 000 inhabitants during this period, Mexico had the sixth highest mortality rate and had officially tested 2.568 million people, reaching 961 938 positive cases.4

People with a previous diagnosis of non-communicable diseases (NCDs) such as high blood pressure (HBP), type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD),5,6 as well as those who are older or male, are more likely to develop serious conditions of COVID-19 or die from this cause.7 In China, the fatality rate (number of deaths per 100 infected) for COVID-19 was 2.3%. However, it was 6.0% for people with hypertension, 7.3% for adults with diabetes and 10.5% for people with cardiovascular disease.8 On the one hand, differences were observed in the hazard ratio (HR) of people who developed severe symptoms or died, being higher in men (HR 1.6) than in women (HR 1.0) and in people ≥65 years old (HR 1.9) as opposed to those <65 years old (HR 1.0).9 Epidemiological studies have shown that the risk of mortality from SARS-Cov-2 increases 2.5 times when the patient has HBP, 1.9 times when they have diabetes10 and 7.9 times when they have CVD.11

In Mexico, the association between obesity and diabetes with a higher risk of SARS-Cov-2 infection,12 severity and need for hospitalization has been documented.13 A recent study has also documented a higher risk of complications at the beginning of hospitalization among patients with SARS-Cov-2 who also had co-morbidities like obesity, hypertension and diabetes.14

In a country like Mexico, where 49% of adults have hypertension,15 14% have diabetes16 and 24% develop CVD,17 it is important to quantify the risk of death among the population with NCDs and COVID-19. It is also important to consider the role of the health system in providing care to patients with SARS-Cov-2 in cases with and without other NCDs. Understanding the magnitude of this association and its related characteristics can improve targeted strategies that aim to identify adults who are most likely to be infected and die of SARS-Cov-2. Our objective is to describe and characterize the association between NCDs and case-fatality rates (CFRs), adjusting by factors that increase the risk of death, such as age and sex, in Mexican adults with a positive diagnosis of SARS-Cov-2.

Methods

Study design and participants

Our study population consisted of Mexican adults aged ≥20 years who tested positive for SARS-Cov-2 and were registered in the Epidemiological Surveillance System for Respiratory Diseases database (SISVER, Spanish acronym). This database includes epidemiological information at the national level, with mandatory reporting of diseases like SARS-Cov-2 for all public or private health units and laboratories. The information was obtained from the Ministry of Health’s website (https://www.gob.mx/salud/documentos/datos-abiertos-152127).18 This data set is open to the public and is continuously updated. We analysed data from the beginning of the epidemic (28 February 2020) to 31 July 2020. The database contains information on all outpatients and those hospitalized, as well as on deaths from SARS-Cov-2 in Mexico.18

Confirmation of COVID-19 cases

Adults were suspected of having COVID-19 if they reported at least two of the following symptoms within the past 7 days: fever, headache and cough, accompanied by at least one of the following signs: arthralgia, conjunctivitis, pain in the chest, dyspnea, myalgia, odynophagia or rhinorrhea. For all suspected cases, two protocols were followed: testing for SARS-Cov-2 and epidemiological surveillance.18 As authorized by the National Committee for Epidemiological Surveillance (CONAVE, Spanish acronym),18 cases were confirmed using the polymerase chain reaction test based on the Berlin protocol.19

NCD assessment

An adult was considered to have an NCD when the patient reported having been previously diagnosed with: HBP, T2D, obesity (OB), CVD, chronic kidney disease (CKD) or COPD. We selected these NCDs because they are those with the highest prevalence in Mexico and because of their association with greater severity of COVID-19.15–17 The instrument used to collect the information was an official standardized questionnaire used by the federal government’s Epidemiological Surveillance System.18 It collects: socio-demographic information (age and sex), personal pathological history (presence of NCDs, date on which the symptoms associated with the infection began and exposure to tobacco), treatment characteristics and indicators of severity such as the presence of pneumonia, need for hospitalization, assistance in the Intensive Care Unit and the use of assisted mechanical intubation (IMA). We classified information on NCDs by number, as follows: no NCDs, one NCD, two NCDs and three or more NCDs.

Institution in which healthcare was provided

We included the institution in which patients received care in the analysis. We categorized the healthcare institutions as Private, Ministry of Navy (SEMAR), Federal Ministry of Health (SS), (Red Cross+DIF+Municipal+University), Ministry of National Defense (SEDENA), not specified, State Secretaries of Health, Petroleos Mexicanos (PEMEX), Institute of Security and Social Services for State Workers (ISSSTE) and Mexican Institute of Social Security (IMSS).

Statistical analysis

Fatality due to SARS-Cov-2 was calculated through the CFR and expressed in percentages (number of deaths from COVID/total patients identified with COVID in the period described × 100) with their 95% confidence intervals (95% CIs).

The CFR was disaggregated by sex, age and NCDs. To assess trends between age groups and the number of NCDs, tests were performed using robust estimates by Bootstrap. The relative risk (RR) was estimated using Poisson models and the probability of death (CFR adjusted) using logistic regression, which in both cases were adjusted in the models for age, sex, the presence of pre-existing diseases (asthma, immunosuppression, other co-morbidities non-specified) and dummy variables for health institutions. Robust estimates were used in all models. Data analysis was performed using the statistical software STATA20 and the statistical software R.21

Results

The database used in this study included information on 842 025 adults aged ≥20 years who were tested for COVID-19. Of these, 3600 (0.4%) observations were eliminated for not having information related to NCD diagnosis. We analysed only information on confirmed SARS-Cov-2 cases (n = 406 966). Of these, 53.2% were men (mean age, 47.0 years: 95% CI, 46.9, 47.1) and 46.5% women (mean age, 45.6 years; 95% CI, 45.6, 45.7).

Participants’ characteristics by sex are described in Table 1. The prevalence of NCDs was similar between the sexes. The most common NCD was HBP (20.6%; 95% CI, 20.5, 20.8), followed by obesity (19.8%; 95% CI, 19.6, 19.8) and diabetes (16.8%; 95% CI, 16.7%, 16.9). Furthermore, 55.8% (95% CI, 55.6, 56.0) reported having no NCDs, whereas 25.9% (95% CI, 25.8, 26.1) reported having one, 12.1% (95% CI, 12.0, 12.3) reported having two and 5.9% (95% CI, 5.9, 6.0) had three or more. Over half of the cases were reported by units from the Ministry of Health (53.7%; 95% CI, 53.5, 53.8), followed by the IMSS (33.0%; 95% CI, 32.8, 33.1).

Table 1.

Characteristics of Mexican adults with diagnosis of COVID-19 and non-communicable diseases (NCDs) by sex

Total
Women
Men
n % (95% CI) N % (95% CI) n % (95% CI)
Total 406 996 100 190 088 46.7 (46.5, 46.8) 216 908 53.2 (53.1, 53.4)
Age in years
 20–39 154 375 37.9 (37.7, 38.0) 75 687 39.8 (39.5, 40.0) 78 688 36.2 (36.0, 36.4)
 40–59 169 361 41.6 (41.4, 41.7) 78 012 41.0 (40.8, 41.2) 91 349 42.1 (41.9, 42.3)
 60–79 72 409 17.7 (17.6, 17.9) 31 508 16.5 (16.4, 16.7) 40 901 18.8 (18.6, 19.0)
 ≥80 10 851 2.6 (2.6, 2.7) 4881 2.5 (2.4, 2.6) 5970 2.7 (2.6, 2.8)
NCDs
Cardiovascular disease
 No 398 168 97.8 (97.7, 97.8) 186 293 98.0 (97.9, 98.0) 211 875 97.6 (97.6, 97.7)
 Yes 8828 2.1 (2.1, 2.2) 3795 1.9 (1.9, 2.0) 5033 2.3 (2.2, 2.3)
Hypertension
 No 323 624 79.5 (79.3, 79.6) 150 661 79.2 (79.0, 79.4) 172 963 79.7 (79.5, 79.9)
 Yes 83 372 20.4 (20.3, 20.6) 39 427 20.7 (20.5, 20.9) 43 945 20.2 (20.0, 20.4)
Chronic kidney diseases
 No 398 660 97.9 (97.9, 97.9) 186 490 98.1 (98.0, 98.1) 212 170 97.8 (97.7, 97.8)
 Yes 8336 2.0 (2.0, 2.0) 3598 1.8 (1.8, 1.9) 4738 2.1 (2.1, 2.2)
Diabetes
 No 339 625 83.4 (83.3, 83.5) 158 970 83.6 (83.4, 83.7) 180 655 83.2 (83.1, 83.4)
 Yes 67 371 16.5 (16.4, 16.6) 31 118 16.3 (16.2, 16.5) 36 253 16.7 (16.5, 16.8)
Obesity
 No 328 251 80.6 (80.5, 80.7) 151 476 79.6 (79.5, 79.8) 176 775 81.4 (81.3, 81.6)
 Yes 78 745 19.3 (19.2, 19.4) 38 612 20.3 (20.1, 20.4) 40 133 18.5 (18.3, 18.6)
Chronic obstructive pulmonary disease
 No 400 352 98.3 (98.3, 98.4) 186 895 98.3 (98.2, 98.3) 213 457 98.4 (98.3, 98.4)
 Yes 6644 1.6 (1.5, 1.6) 3193 1.6 (1.6, 1.7) 3451 1.5 (1.5, 1.6)
Number of NCDs
 0 241 589 59.3 (59.2, 59.5) 113 244 59.5 (59.3, 59.7) 128 345 59.1 (58.9, 59.3)
 1 100 464 24.6 (24.5, 24.8) 45 600 23.9 (23.7, 24.1) 54 864 25.2 (25.1, 25.4)
 2 45 673 11.2 (11.1, 11.3) 21 545 11.3 (11.1, 11.4) 24 128 11.1 (10.9, 11.2)
 ≥3 19 270 4.7 (4.6, 4.7) 9699 5.1 (5.0, 5.2) 9571 4.4 (4.3, 4.4)
Severity indicators
Pneumonia
 No 321 109 78.8 (78.7, 79.0) 157 201 82.7 (82.5, 82.8) 163 908 75.5 (75.3, 75.7)
 Yes 85 881 21.1 (20.9, 21.2) 32 884 17.2 (17.1, 17.4) 52 997 24.4 (24.2, 24.6)
Attention mode
Ambulatory 294 586 72.3 (72.2, 72.5) 146 841 77.2 (77.0, 77.4) 1477 45 68.1 (67.9, 68.3)
 Hospital admission 112 410 27.6 (27.4, 27.7) 43 247 22.7 (22.5, 22.9) 69 163 3.2 (31.6, 32.0)
Mechanically assisted intubation
 No 396 337 97.3 (97.3, 97.4) 186 528 98.1 (98.0, 98.1) 209 809 96.7 (96.6, 96.8)
 Yes 10 659 2.6 (2.5, 2.6) 3560 1.8 (1.8, 1.9) 7099 3.2 (3.1, 3.3)
Admitted to unit and intensive care
 No 398 193 97.8 (97.7, 97.8) 187 060 98.4 (98.3, 98.4) 211 133 97.3 (97.2, 97.4)
 Yes 8803 2.1 (2.1, 2.2) 3028 1.5 (1.5, 1.6) 5775 2.6 (2.5, 2.7)
Institutions of the health system
 Private 11 992 2.9 (2.8, 2.9) 4790 2.5 (2.4, 2.5) 7202 3.3 (3.2, 3.3)
 SEMAR 3184 0.7 (0.7, 0.8) 1040 0.5 (0.5, 0.5) 2144 0.9 (0.9, 1.0)
 SS 218 544 53.6 (53.5, 53.8) 104 574 55.0 (54.7, 55.2) 113 970 52.5 (52.3, 52.7)
 Others 762 0.1 (0.1, 0.2) 380 0.1 (0.1, 0.2) 382 0.1 (0.1, 0.1)
 SEDENA 2831 0.6 (0.6, 0.7) 943 0.4 (0.4, 0.5) 1888 0.8 (0.8, 0.9)
 Not specified 3148 0.7 (0.7, 0.8) 1416 0.7 (0.7, 0.7) 1732 0.7 (0.7, 0.8)
 SMH 9186 2.2 (2.2, 2.3) 4537 2.3 (2.3, 2.4) 4649 2.1 (2.0, 2.2)
 PEMEX 5106 1.2 (1.2, 1.2) 1793 0.9 (0.8, 0.9) 3313 1.5 (1.4, 1.5)
 ISSSTE 18 026 4.4 (4.3, 4.4) 8401 4.4 (4.3, 4.5) 9625 4.4 (4.3, 4.5)
 IMSS 134 217 32.9 (32.8, 33.1) 62 214 32.7 (32.5, 32.9) 72 003 33.1 (32.9, 33.3)

Data from General Direction of Health Information (DGIS), 2020.

Ministry of Health, Ministry of the Navy (SEMAR), Federal Ministry of Health (SS), Other (Red Cross, DIF, Municipal, Universitary), Ministry of National Defense (SEDENA), Statal Ministry of Health (SMH), Petroleos Mexicanos (PEMEX), Institute of Security and Social Services for State Workers (ISSSTE), Mexican Institute of Social Security (IMSS).

Table 2 shows the CFR for SARS-Cov-2 by sex and NCDs. In the total population, the average CFR was 12.1% (95% CI, 12.0, 12.2) and was higher among men (CFR 14.6%; 95% CI, 14.5, 14.8) than women (CFR 9.1%; 95% CI, 9.0, 9.3). Trend analyses showed that the CFR increased with age and number of NCDs (trend test p < 0.001). In women, the CFR was 1.2% in the 20- to 39-year-old age group and 40.8% in the ≥80 years group, whereas, for men, it was 2.6% and 47.9%, respectively.

Table 2.

Case-fatality rate (CFR) in Mexican adults diagnosed with COVID-19 and non-communicable diseases (NCDs) by sex.

Total
Women
Men
Womena vs men
n CFR % (95% CI) RRb (95% CI)d n CFR % (95% CI) RRc (95% CI)d N CFR % (95% CI)d RRc (95% CI) RR by sex (95% CI)d P-valuef
Sex 406 996 11.2 (11.1, 11.3) 190 088 8.4 (8.3, 8.6) 216 908 13.7 (13.6, 13.9) 1.5 (1.4, 1.5) <0.001
Age group
  20–39a 154 375 1.7 (1.6, 1.8) 1 75 687 1.1 (1.0, 1.1) 1 78 688 2.3 (2.1, 2.5) 1 2.0 (1.9, 2.2) <0.001
  40–59 169 361 9.8 (9.6, 9.9) 5.5 (5.3, 5.7) 78 012 6.7 (6.7, 6.8) 6.1 (5.6, 6.5) 91 349 12.4 (12.2, 12.6) 5.2 (4.9, 5.4) 1.7 (1.7, 1.8) <0.001
  60–79 72 409 30.2 (29.9, 30.6) 16.8 (16.2, 17.5) 31 508 25.7 (25.6, 5.8) 23.2 (21.6, 24.8) 40 901 33.7 (33.5, 34.0) 14.1 (13.5, 14.8) 1.3 (1.2, 1.3) <0.001
  ≥80 10 851 43.2 (42.3, 44.2) 24.2 (23.1, 25.2) 4881 39.0 (38.9, 9.0) 35.1 (32.6, 37.9) 5970 46.7 (46.5, 46.9) 19.6 (18.6, 20.6) 1.1 (1.1, 1.2) <0.001
p trend p < 0.001 p < 0.001 p < 0.001       p < 0.001
NCCDs
Cardiovascular disease
  Noa 398 168 10.9 (10.8, 11.0) 1 186 293 8.1 (8.0, 8.2) 1 211 875 13.3 (12.0, 14.6) 1 1.5 (1.5, 1.5) <0.001
  Yes 8828 27.7 (26.7, 28.6) 1.1 (1.0, 1.1) 3795 24.0 (23.8, 4.1) 1.2 (1.1, 1.3) 5033 30.4 (29.2, 31.7) 1.1 (1.1, 1.2) 1.2 (1.1, 1.3) <0.001
Hypertension
  Noa 323 624 7.9 (7.8, 8.0) 1 150 661 5.1 (5.0, 5.2) 1 172 963 10.4 (9.9, 10.8) 1 1.7 (1.6, 1.7) <0.001
  Yes 83 372 24.2 (23.9, 24.5) 1.4 (1.4, 1.5) 39 427 21.2 (21.0, 1.3) 1.6 (1.6, 1.7) 43 945 26.9 (26.5, 27.3) 1.3 (1.3, 1.3) 1.3 (1.2, 1.3) <0.001
Chronic kidney diseases
  Noa 398 660 10.7 (10.6, 10.8) 1 186 490 7.9 (7.8, 8.1) 1 212 170 13.1 (11.7, 14.5) 1 1.5 (1.5, 1.5) <0.001
  Yes 8336 37.5 (36.5, 38.6) 2.0 (2.0, 2.1) 3598 34.8 (34.7, 34.9) 2.4 (2.3, 2.6) 4738 39.6 (38.2, 41.0) 1.8 (1.8, 1.9) 1.1 (1.0, 1.1) <0.001
Diabetes
  Noa 339 625 8.3 (8.2, 8.4) 1 158 970 5.6 (5.5, 5.8) 1 180 655 10.7 (10.2, 11.2) 1 1.6 (1.6, 1.7) <0.001
  Yes 67 371 26.0 (25.6, 26.3) 1.7 (1.6, 1.7) 31 118 22.7 (22.6, 22.8) 1.9 (1.9, 2.0) 36 253 28.7 (28.3, 29.2) 1.5 (1.5, 1.6) 1.2 (1.2, 1.3) <0.001
Obesity
  Noa 328 251 10.5 (10.4, 10.6) 1 151 476 7.5 (7.4, 7.6) 1 176 775 13.1 (12.6, 13.4) 1 1.5 (1.5, 1.5) <0.001
  Yes 78 745 14.5 (14.2, 14.7) 1.4 (1.4, 1.4) 38 612 12.1 (11.9, 12.2) 1.5 (1.4, 1.5) 40 133 16.8 (16.4, 17.2) 1.4 (1.3, 1.4) 1.4 (1.4, 1.5) <0.001
Chronic obstructive pulmonary disease
  Noa 400 352 10.9 (10.8, 11.0) 1 186 895 8.1 (7.9, 8.2) 1 213 457 13.3 (11.7, 14.9) 1 1.5 (1.5, 1.5) <0.001
  Yes 6644 33.3 (32.2, 34.5) 1.1 (1.1, 1.2) 3193 30.0 (29.8, 30.1) 1.2 (1.1, 1.2) 3451 36.5 (34.9, 38.1) 1.1 (1.0, 1.1) 1.2 (1.1, 1.3) <0.001
Number of NCCDs
 0a 241 589 5.8 (5.7, 5.9) 1 113 244 3.4 (3.3, 3.5) 1 128 345 8.0 (7.7, 8.3) 1 1.9 (1.8, 1.9) <0.001
 1 100 464 14.3 (14.1, 14.5) 1.6 (1.5, 1.6) 45 600 10.6 (10.5, 10.7) 1.8 (1.7, 1.9) 54 864 17.4 (17.1, 17.7) 1.5 (1.4, 1.5) 1.5 (1.5, 1.6) <0.001
 2 45 673 24.1 (23.7, 24.5) 2.0 (1.9, 2.1) 215 45 20.7 (20.6, 20.8) 2.5 (2.4, 2.6) 241 28 27.2 (26.8, 27.5) 1.7 (1.7, 1.8) 1.3 (1.2, 1.3) <0.001
  >2 19 270 32.8 (32.1, 33.5) 2.4 (2.4, 2.5) 9699 29.9 (29.8, 30.0) 3.2 (3.0, 3.3) 9571 35.8 (35.4, 36.1) 2.1 (2.0, 2.2) 1.2 (1.1, 1.2) <0.001
p trend p < 0.001 p < 0.001 p < 0.001
Severity indicators
Pneumonia
  Noa 321 109 3.6 (3.5, 3.6) 1 157 201 2.5 (2.4, 2.6) 1 163 908 4.6 (4.1, 5.0) 1 1.7 (1.6, 1.7) <0.001
  Yes 85 881 40.0 (39.7, 40.3) 6.6 (6.5, 6.8) 32 884 36.7 (36.6, 36.8) 8.1 (7.8, 8.4) 52 997 42.1 (41.6, 42.4) 5.9 (5.7, 6.0) 1.1 (1.1, 1.1) <0.001
Attention mode
Hospital admission
  Noa 294 586 1.7 (1.6, 1.7) 1 146 841 1.1 (1.1, 1.2) 1 147 745 2.2 (1.9, 2.6) 1 1.9 (1.7, 2.0) <0.001
  Yes 112 410 36.3 (36.0, 36.6) 12.9 (12.5, 13.3) 43 247 33.2 (33.2, 33.3) 16.7 (15.9, 17.7) 69 163 38.2 (37.8, 38.6) 11.0 (10.5, 11.4) 1.1 (1.1, 1.1) <0.001
Mechanically assisted intubation
  Noa 396 337 9.6 (9.5, 9.7) 1 186 528 7.2 (7.1, 7.3) 1 209 809 11.7 (10.7, 12.7) 1 1.5 (1.4, 1.5) <0.001
  Yes 10 659 73.1 (72.2, 73.9) 4.1 (4.0, 4.2) 3560 72.8 (72.6, 72.9) 4.8 (4.6, 5.0) 7099 73.2 (72.2, 74.2) 3.8 (3.7, 3.9) 1 (0.9, 1.0) 0.0614
Admitted to unit and intensive care
  Noa 398 193 10.3 (10.3, 10.4) 1 187 060 7.8 (7.7, 7.9) 1 211 133 12.6 (11.3, 13.9) 1 1.5 (1.4, 1.5) <0.001
  Yes 8803 51.9 (50.9, 53.0) 2.8 (2.7, 2.9) 3028 48.8 (48.7, 48.9) 3.1 (2.9, 3.2) 5775 53.6 (52.3, 54.9) 2.7 (2.6, 2.7) 1.1 (1.0, 1.1) <0.001
Institutions of the health systeme
 Private 11 992 4.6 (4.3, 5.0) 1 4790 3.7 (3.2, 4.3) 1 7202 5.2 (4.3, 6.2) 1 1.5 (1.2, 1.7) <0.0001
 SEMAR 3184 5.9 (5.1, 6.7) 1.4 (1.2, 1.6) 1040 7.0 (6.4, 7.5) 1.9 (1.4, 2.4) 2144 5.4 (4.4, 6.4) 1.2 (0.9, 1.4) 1 (0.7, 1.3) 0.4882
 SS 218 544 6.3 (6.2, 6.4) 1.5 (1.4, 1.6) 104 574 4.4 (3.9, 5.0) 1.4 (1.2, 1.6) 113 970 8.1 (7.1, 9.0) 1.6 (1.5, 1.8) 1.7 (1.6, 1.8) <0.0001
 Others 762 8.0 (6.1, 9.9) 1.3 (1.0, 1.7) 380 5.5 (4.9, 6.0) 1.2 (0.8, 1.9) 382 10.4 (9.5, 11.4) 1.4 (1.0, 1.9) 1.6 (1.0, 2.6) 0.0225
 SEDENA 2831 11.2 (10.1, 12.4) 2.2 (1.9, 2.5) 943 11.1 (10.5, 11.6) 2.5 (2.0, 3.1) 1888 11.3 (10.3, 12.2) 2.1 (1.8, 2.4) 1.1 (0.9, 1.4) 0.0623
 Not specified 3148 11.8 (10.7, 13.0) 2.3 (2.1, 2.6) 1416 7.9 (7.4, 8.5) 2.3 (1.8, 2.8) 1732 15.1 (14.1, 16.0) 2.4 (2.1, 2.8) 1.5 (1.3, 1.9) <0.0001
 SMH 9186 11.9 (11.2, 12.6) 2.5 (2.3, 2.8) 4537 8.7 (8.2, 9.3) 2.5 (2.2, 3.0) 4649 15.0 (14.1, 16.0) 2.6 (2.3, 2.9) 1.5 (1.3, 1.6) <0.0001
 PEMEX 5106 14.9 (14.0, 15.9) 2.3 (2.1, 2.6) 1793 14.3 (13.7, 14.8) 2.6 (2.2, 3.1) 3313 15.3 (14.3, 16.2) 2.2 (2.0, 2.5) 1.2 (1.1, 1.4) 0.0032
 ISSSTE 18 026 17.9 (17.4, 18.5) 2.9 (2.7, 3.2) 8401 13.7 (13.1, 14.2) 2.9 (2.5, 3.3) 9625 21.6 (20.7, 22.6) 2.9 (2.7, 3.3) 1.4 (1.3, 1.5) <0.0001
 IMSS 134 217 18.9 (18.7, 19.1) 3.8 (3.5, 4.1) 62 214 14.7 (14.1, 15.2) 4.0 (3.5, 4.6) 72 003 22.6 (21.6, 23.6) 3.7 (3.4, 4.1) 1.4 (1.3, 1.4) <0.0001
a

Reference category.

b

RR = relative risk adjusted by age and sex.

c

RR adjusted by age.

d

RR = relative risk with 95% confidence interval.

e

Ministry of Health. Ministry of the Navy (SEMAR), Federal Ministry of Health (SS), Other (Red Cross, DIF, Municipal, Universitary), Ministry of National Defense (SEDENA), Statal Ministry of Health (SMH), Petroleos Mexicanos (PEMEX), Institute of Security and Social Services for State Workers (ISSSTE), Mexican Institute of Social Security (IMSS).

f

Differences women vs men.

Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

In the group of patients without NCDs and stratified by sex, the CFR was lower in women (3.4%; 95% CI, 3.3, 3.5) than in men (8.0%; 95% CI, 7.8, 8.1). When stratifying by type of institution, the CFR was higher in the IMSS (CFR , 10.7%; 95% CI, 10.5, 10.9), followed by the ISSSTE (CFR, 9.5%; 95% CI, 8.9, 10.1). In patients with at least three NCDs, the CFR was higher in women (CFR, 29.9%; 95% CI, 29.0, 30.0) than in men (CFR, 35.8%; 95% CI, 34.8, 36.7), whereas, when stratifying by type of institution, the CFR was higher in the IMSS (CFR, 44.0%; 95% CI, 42.9, 45.1), followed by the ISSSTE (CFR, 37.5%; 95% CI, 35.0, 40.1). The trend test by number of NCDs was p < 0.001 (Table 3).

Table 3.

Case-fatality rate (CFR) in Mexican adults diagnosed with COVID-19 and categorized by number of non-communicable diseases (NCDs)

Variables No NCDs
One NCD
Two NCDs
Three NCDs
Among NCDs
N CFR % (95% CI) RR n CFR % (95% CI) RR (95% CI) N CFR % (95% CI) RR (95% CI) n CFR % (95% CI) RR (95% CI) p trend
Sexc
Womena 113 244 3.4 (3.3, 3.5) 1.0 45 600 10.6 (10.3, 10.9) 1.8 (1.7, 1.9) 21 545 20.7 (20.2, 21.3) 2.5 (2.5, 2.4) 9699 29.9 (29.0, 30.8) 3.2 (3.0, 3.3) <0.0001
Men 128 345 8.0 (7.8, 8.1) 1.0 54 864 17.4 (17.1, 17.7) 1.5 (1.4, 1.5) 24 128 27.2 (26.6, 27.7) 1.7 (1.7, 1.7) 9571 35.8 (34.8, 36.7) 2.1 (2.0, 2.2) <0.0001
Age groupd (years)
  20–39a 120 764 0.9 (0.9, 1.0) 1.0 27 670 3.4 (3.2, 3.7) 3.5 (3.2, 3.8) 4924 8.3 (7.5, 9.0) 8.2 (8.2, 7.3) 1017 16.3 (14.0, 18.5) 16.1 (13.8, 18.7) <0.0001
  40–59 93 176 6.0 (5.9, 6.2) 1.0 47 162 11.3 (11.0, 11.6) 1.8 (1.8, 1.9) 20 849 16.9 (16.4, 17.4) 2.8 (2.8, 2.7) 8174 25.5 (24.5, 26.4) 4.2 (4.0, 4.4) <0.0001
  60–79 24 373 24.9 (24.3, 25.4) 1.0 22 093 29.4 (28.8, 30.0) 1.1 (1.1, 1.2) 17 169 34.1 (33.4, 34.8) 1.4 (1.4, 1.3) 8774 39.6 (38.6, 40.6) 1.6 (1.6, 1.7) <0.0001
  ≥80 3276 39.4 (37.7, 41.1) 1.0 3539 44.5 (42.8, 46.1) 1.1 (1.0, 1.2) 2731 45.0 (43.1, 46.9) 1.1 (1.1, 1.1) 1305 45.9 (43.1, 48.6) 1.1 (1.1, 1.2) <0.0001
Severity indicators
Pneumoniaa
  Noa 208 529 1.7 (1.7, 1.8) 1.0 73 721 4.7 (4.5, 4.8) 1.6 (1.5, 1.7) 28 437 9.8 (9.5, 10.2) 2.3 (2.3, 2.2) 10 422 15.7 (15.0, 16.4) 3.2 (3.0, 3.4) <0.0001
  Yes 33 056 31.8 (31.3, 32.3) 1.0 26 742 40.9 (40.3, 41.5) 1.1 (1.1, 1.1) 17 235 47.7 (46.9, 48.4) 1.2 (1.2, 1.2) 8848 52.9 (51.9, 54.0) 1.3 (1.3, 1.4) <0.0001
Attention mode
Hospital admissiona
  Noa 198 400 0.8 (0.7, 0.8) 1.0 65 886 2.3 (2.2, 2.5) 1.7 (1.6, 1.9) 22 767 5.2 (4.9, 5.5) 2.6 (2.6, 2.4) 7533 9.1 (8.4, 9.7) 3.8 (3.5, 4.2) <0.0001
  Yes 43 189 29.0 (28.6, 29.4) 1.0 34 578 37.1 (36.6, 37.6) 1.1 (1.1, 1.1) 22 906 42.9 (42.2, 43.5) 1.2 (1.2, 1.2) 11 737 48.0 (47.1, 48.9) 1.3 (1.3, 1.4) <0.0001
Mechanically assisted intubationa
  Noa 238 182 4.9 (4.8, 5.0) 1.0 96 958 12.2 (11.9, 12.4) 1.5 (1.5, 1.6) 43 224 21.2 (20.8, 21.6) 2.0 (2.0, 1.9) 17 973 29.5 (28.8, 30.1) 2.5 (2.4, 2.6) <0.0001
  Yes 3407 68.6 (67.0, 70.2) 1.0 3506 73.6 (72.2, 75.1) 1.0 (1.0, 1.0) 2449 75.2 (73.5, 76.9) 1.0 (1.0, 1.0) 1297 79.1 (76.8, 81.3) 1.1 (1.0, 1.1) <0.0001
Admitted to unit and intensive caree
  Noa 238 685 5.3 (5.2, 5.4) 1.0 97 496 13.1 (12.9, 13.3) 1.5 (1.5, 1.6) 43 750 22.8 (22.4, 23.2) 2.0 (2.0, 1.9) 18 262 31.2 (30.5, 31.9) 2.5 (2.4, 2.5) <0.0001
  Yes 2904 46.2 (44.3, 48.0) 1.0 2968 52.6 (50.8, 54.4) 1.0 (1.0, 1.1) 1923 54.6 (52.4, 56.8) 1.1 (1.1, 1.0) 1008 61.7 (58.7, 64.7) 1.2 (1.1, 1.3) <0.0001
Institutions of the health systembe,b
Privatea 7994 1.9 (1.6, 2.2) 1.0 2555 6.6 (5.6, 7.6) 2.1 (1.6, 2.6) 1038 14.2 (12.1, 16.3) 3.2 (3.2, 2.5) 405 21.9 (17.9, 26.0) 4.2 (3.2, 5.5) <0.0001
SEMAR 2407 2.0 (1.5, 2.6) 1.0 461 13.6 (10.5, 16.8) 3.4 (2.3, 5.1) 215 21.8 (16.3, 27.3) 3.7 (3.7, 2.4) 101 29.7 (20.7, 38.6) 4.8 (3, 7.9.0)
SS 136 772 3.1 (3.0, 3.2) 1.0 53 198 8.9 (8.6, 9.1) 1.9 (1.8, 1.9) 21 062 15.3 (14.8, 15.8) 2.4 (2.4, 2.3) 7512 20.7 (19.8, 21.6) 3.1 (2.9, 3.3) <0.0001
Others 413 2.6 (1.1, 4.2) 1.0 190 12.6 (7.8, 17.3) 2.9 (1.4, 5.7) 101 13.8 (7.0, 20.6) 2.0 (2.0, 0.8) 58 20.6 (10.1, 31.2) 3.0 (1.3, 6.8) <0.0001
SEDENA 1827 7.2 (6.0, 8.4) 1.0 603 15.2 (12.3, 18.1) 1.2 (0.9, 1.6) 300 24.6 (19.7, 29.5) 1.4 (1.4, 1.0) 101 19.8 (11.9, 27.6) 1.2 (0.7, 1.9) <0.0001
Not specified 1681 6.7 (5.5, 7.9) 1.0 907 14.7 (12.4, 17.0) 1.4 (1.1, 1.8) 398 20.8 (16.8, 24.8) 1.6 (1.6, 1.2) 162 26.5 (19.7, 33.3) 1.7 (1.2, 2.4) <0.0001
SMH 5308 7.1 (6.4, 7.8) 1.0 2253 14.2 (12.7, 15.6) 1.3 (1.1, 1.5) 1076 20.9 (18.4, 23.3) 1.4 (1.4, 1.2) 549 31.3 (27.4, 35.2) 1.6 (1.4, 1.9) <0.0001
PEMEX 1502 6.9 (5.6, 8.2) 1.0 1970 12.2 (10.7, 13.6) 1.3 (1.1, 1.6) 984 21.6 (19.0, 24.2) 1.7 (1.7, 1.3) 650 31.8 (28.2, 35.4) 2.1 (1.7, 2.6) <0.0001
ISSSTE 9079 9.5 (8.9, 10.1) 1.0 4756 20.9 (19.8, 22.1) 1.4 (1.3, 1.6) 2799 30.5 (28.8, 32.2) 1.7 (1.7, 1.6) 1392 37.5 (35.0, 40.1) 2.1 (1.9, 2.3) <0.0001
IMSS 74 606 10.7 (10.5, 10.9) 1.0 33 571 22.7 (22.2, 23.1) 1.4 (1.3, 1.4) 17 700 34.7 (34.0, 35.4) 1.6 (1.6, 1.5) 8340 44.0 (42.9, 45.1) 1.9 (1.8, 1.9) <0.0001

Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

a

Reference category.

b

Ministry of Health, Ministry of the Navy (SEMAR), Federal Ministry of Health (SS), Other (Red Cross, DIF, Municipal, Universitary), Ministry of National Defense (SEDENA), Statal Ministry of Health (SMH), Petroleos Mexicanos (PEMEX), Institute of Security and Social Services for State Workers (ISSSTE), Mexican Institute of Social Security (IMSS). cAdjusted by age continuous. dAdjusted by sex. eAdjusted by age continuous and sex.

Figure 1 shows that the CFR increases with the number of NCDs in a triple interaction (p < 0.01) with sex and age. Adults aged 20–29 years with at least three NCDs have a greater risk compared with those without NCDs, in women (RR, 46.6; 95% CI, 28.2, 76.9) and men (RR, 16.5; 95% CI, 9.9, 27.3). Moreover, the risk among adults aged ≥80 years with at least three NCDs compared with those without NCDs is 1.2 in women (95% CI, 1.0, 1.3) and 1.0 in men (95% CI, 0.9, 1.1). The model is shown in Supplementary Appendix 1, available as Supplementary data at IJE online, and Table 1.

Figure 1.

Figure 1

Case-fatality rate (CFR) estimate in adults with COVID-19 and number of non-communicable diseases (NCDs), categorized by age groups and sex. Estimations adjusted by categories of the institutions of the health system, asthma, immunosuppression and other non-specified co-morbidities. RR, relative risk (95% IC) no NCDs vs three or more NCDs. Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

The CFR for SARS-Cov-2 in men and women by number and all possible combinations of NCDs is shown in Supplementary Appendix 2, available as Supplementary data at IJE online, and Table 1. For two NCDs, the combination with the greatest CFR was T2D+CKD (CFR, 44.0; 95% CI, 39.2, 48.8); for three NCDs, it was T2D+COPD+CVD (CFR, 57.5; 95% CI, 38.4, 75.8).

When categorizing by number of NCDs (from none to at least three), and disaggregating by age group, a greater risk of mortality for older age was found in all categories, except for T2D+COPD and CVD+CKD combinations. The combinations with the highest CFR (from 50.0% to 75.0%) were: CVD+HBP+CKD+T2D+OB, CVD+CKD+COPD, CVD+T2D+COPD, CVD+HBP+CKD+OB+COPD, HBP+CKD+T2D+OB+COPD, CVD+CKD+T2D+COPD; and 31 combinations with CFR between 30.0% and 49.0% were observed. The lowest CFRs were with OB or no NCDs (Figure 2). We did not see a specific pattern by sex (Supplementary Appendix 3, available as Supplementary data at IJE online, and Figures 1 and 2).

Figure 2.

Figure 2

Case-fatality rate and combinations of non-communicable diseases (NCDs) by age groups. Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

Figures 3–5 show the CFR by age groups for each NCD (T2D, HBP, OB, CKD, COPD and CVD) individually and combined with other NCDs. Figure 3a and b shows that younger adults had a higher RR of death when they had T2D combined with one or more NCDs (women: RR, 12.5; 95% CI, 7.1, 22.2; men: RR, 5.8, CI 95% 3.1, 10.9). A similar pattern was observed in all diseases and combinations in the age group of ≥60 years. The model is shown in Supplementary Appendix 1, available as Supplementary data at IJE online, and Table 2.

Figure 3.

Figure 3

Case-fatality rate (CFR) in adults with COVID-19 with/without diabetes or hypertension, with/without other non-communicable diseases (NCDs). Estimations adjusted by categories of the institutions of the health system, asthma, immunosuppression and other non-specified co-morbidities. Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

Figure 4.

Figure 4

Case-fatality rate (CFR) in adults with COVID-19 with/without obesity or chronic kidney disease, with/without other non-communicable diseases (NCDs). Estimations adjusted by categories of the institutions of the health system, asthma, immunosuppression and other non-specified co-morbidities. Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

Figure 5.

Figure 5

Case-fatality rate (CFR) in adults with COVID-19 with/without chronic obstructive pulmonary disease or cardiovascular disease, with/without other non-communicable diseases (NCDs). Estimations adjusted by categories of the institutions of the health system, asthma, immunosuppression and other non-specified co-morbidities. Data from General Direction of Health Information (DGIS), Ministry of Health, 2020.

Discussion

In our analysis, the CFR was associated with sex, age and number of NCDs (HBP, obesity, CVD, CKD or COPD). We observed greater CFR heterogeneity among institutions.

There is evidence that a country’s average age can explain up to 66% of the variation in CFR for COVID-19.22 Much of the variation between countries is due to the age of people evaluated and diagnosed with the virus. In our analysis, the average age of the population infected with SARS-Cov-2 was 45 years, similarly to that in China (49 years) but younger than that in Italy (62 years).2 This could be due to the fact that the median age is similar in Mexico (30 years)3 and China (35 years),4 but higher in Italy (46 years).4

Adults with underlying NCDs are more likely to experience more severe symptoms or die from a SARS-Cov-2 infection.23 In our analysis, 40.5% of adults with SARS-Cov-2 had at least one NCD. This is lower than the prevalence found in the general Mexican adult population, in which 49.2% have at least one NCD.24

On the other hand, men have fewer antibodies that decrease the expression of IL-6, which is linked to deregulation of the immune system and lung damage. Likewise, men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in the alveolar membrane of the lungs through which SARS-CoV-2 enters and infects its host.25 Consistently with this infection mechanism and men’s diminished immune-system response, the CFR in our study was higher in men (CFR, 14.6) than in women (CFR, 9.1).

The number of chronic co-morbidities influences the risk of being infected with SARS-Cov-2 and dying from it.26 People with more NCDs and of older age have a higher risk of death.10 In China, reports indicate that, among people ≥60 years old, the risk of death was greater among those with two or more NCDs (RR, 2.59) in comparison to those with only one NCD (RR, 1.79).11–16 This is consistent with our findings, where risk of death was also greater in adults ≥60 years old and those with two or more NCDs (RR, 24.1) vs those with one (RR, 14.3).

Regardless of age, adults with SARS-Cov-2 and co-morbidities are at increased risk of death. Adults with SARS-Cov-2 and COPD have a higher expression of the functional receptor in the lower respiratory tract and this explains the extent of damage and the increased risk of death in patients with COPD and SARS-CoV-2.27 COPD combined with CVD or CKD significantly increases the risk of death, due to the systemic inflammatory response induced by hypoxia, as well as the homeostatic imbalance caused by CKD.28–30 The combination of three NCDs with the highest CFR among Mexicans was CVD+T2D+COPD. This combination is one of the most common in adults worldwide28 and can be attributed to the fact that multiorgan failure is associated with elevated plasminogen levels, leading to coronary thrombosis and pulmonary embolism.31 In general, we found that a greater number of NCDs increases the CFR because it reflects multiple-organ dysfunction, severity and worse prognosis. 32,33

We observe a triple interaction between the number of NCDs, age and sex. In the group aged 20–29 years, the RR of death when having at least three NCDs compared with not having any NCDs was higher in women (RR, 46.6) than in men (RR, 16.5), unlike that in the age group ≥80 years old, in which the RR was similar between women (RR, 1.0) and men (RR, 1.2). The greater RR in women aged 20–29 years is explained by the low CFR when they did not have any NCDs (women, 0.37%; men, 0.82%) and the higher CFR observed in women when they presented with at least three NCDs (women, 16.9%; men, 12.9%). In the youngest age group (20–29 years), women with at least NCDs had a higher CFR than men. This can be explained because the youngest have risk behaviours such as high alcohol and tobacco consumption that contribute to the generation of NCDs at very early ages34 but, in Mexico, these risk behaviours are more frequent in women than in men.35,36

We observed similar associations in other publications that use the same sources.13–14–15–37 However, our research was an exhaustive analysis that focused on the effect of six NCDs. This considers that they have a similar physiopathology, based on expression of ACE2 and a deficient immune system in diabetics that delays the phagocytic and antibacterial activity of neutrophils and macrophages together with oxidative stress that also exacerbates the chronic inflammatory processes.37,38 Thus, the smoking variable was eliminated because we do not believe it captures the tobacco habit in a robust way, as proposed by international expert recommendations.39

In Mexico, the difference observed in the CFR by institution providing health services may be due to the type of users treated (with formal employment or without employment, with different levels of poverty and different ages of the beneficiaries). It could also be due to the limited material and personnel infrastructure that local public institutions have (less testing capacity, especially at the beginning of the pandemic). In comparison, federal public institutions and private institutions have more availability of therapeutic supplies and intensive-care equipment. In our study, the CFR was lower in private institutions and federal public institutions. To explain these differences in more detail, a more comprehensive analysis is needed in the future.40,41

Limitations

We acknowledge that the main limitation of our study lies within its design, considering it is an observational study. This impedes us from making precise inferences or assuming causal relationships. We lacked information on clinical biomarkers at the time of registration to evaluate the baseline health status of the patients with SARS-Cov-2. With this information, we could have estimated, with less error and/or confounders, the effect of NCDs on mortality from SARS-Cov-2.

Another possible limitation is due to the data source, which was compiled through the Ministry of Health Epidemiologic Surveillance System and favours surveillance of high-risk cases or specific risk factors. This increases the probability of registering cases with severe symptoms and under-representing cases with lower risk who have moderate symptoms.

A third limitation of this study is that, to preserve the confidentiality of participants, the database does not include the specific medical unit in which the patients received care. It did not allow us to control for the specific effect of each healthcare unit and the clustering of observations at the healthcare unit, which may affect mainly the variance of our estimates.

A strength of our study is that it is the first to examine the association between CFR and NCDs in SARS-Cov-2 patients by correcting for the institution of care in all data of Mexican adults registered as SARS-Cov-2-positive. Our findings are consistent with those of other publications that state that NCDs increase mortality in SARS-Cov-2 cases. It therefore contributes to a better understanding of the interaction between SARS-Cov-2 and pre-existing NCDs.

Conclusion

We found that, among Mexican adults, mortality from SARS-Cov-2 increases with the number of NCDs. The combination of diseases such as T2D, CKD, COPD and CVD that were diagnosed in young people may mean that Mexicans are exposed early to risk factors like alcohol and tobacco intake, adiposity and poor diet, and in greater magnitude. This accelerates disease onset and may explain the higher mortality in young Mexicans. Our findings are consistent with the scientific literature and contribute to the understanding of these associations. More studies are needed to understand the heterogeneity observed by mortality and type of health institution. The evidence generated by this study can be useful for decision makers in the health sector, at both population and clinical levels.

Ethics approval

The study does not require ethical review because it is based on open, anonymized data from the Mexican Ministry of Health.

Supplementary data

Supplementary data are available at IJE online.

Author contributions

E.M.F., M.R.V., S.B.C. and I.C.N.: conceptualized the research; E.M.F. and B.H.: analysed the data; M.R.V., J.E.M. and I.C.N.: investigation; M.R.V., J.E.M., I.C.N., E.M.F. and I.C.N.: methodology; M.R.V., J.E.M., I.C.N. and E.M.F.: supervision; E.M.F., M.R.V., J.E.M., B.H., S.B.C., V.E.V.D. and I.C.N.: writing, review and editing.

Funding

We did not receive funding for this investigation.

Supplementary Material

dyab008_Supplementary_Data

Acknowledgements

The original data are public in https://www.gob.mx/salud/documentos/datos-abiertos-152127.

Conflict of interest

None declared.

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