INTRODUCTION

In Peru, the first wave of the 2019 coronavirus disease pandemic (COVID-19) began on March 6, 2020. Since then, Peru has experienced five waves with more than four million people infected, of which almost three hundred thousand required hospitalization ¹. COVID-19 took the Peruvian health system by surprise and caused the collapse of hospitals right at the beginning of the pandemic. Nationally, there were only about one hundred intensive care beds and oxygen volume production was limited ². The government responded to this situation with several measures, including restricting mobilization and reinforcing the health system ³. Within four months, the number of intensive care beds was increased to almost 1000 ². However, the number of cases increased again in November, triggering a second wave, with almost two million cumulative cases and almost 200,000 deaths ¹.

The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic infection to severe disease; the highest percentage of cases are asymptomatic, mild or moderate, but there is a group of patients who develop severe disease, require hospital management and have a higher risk of death ⁴. Studies in different populations, have shown that the following are risk factors for mortality from COVID-19: older age, male sex, comorbidities such as obesity, cardiovascular disease, cancer, chronic kidney disease, immunosuppression, as well as clinical factors such as oxygen saturation at hospital admission, elevated creatinine and lactate dehydrogenase (LDH) levels ^5-8. In addition, the collapse of the healthcare system also played a crucial role in mortality.

Understanding the main factors that increase the risk of death is crucial to improve the health system response. Few studies have investigated the factors associated with mortality in different age groups. In this study, we sought to evaluate comorbidities associated with mortality in adult patients hospitalized in the provinces of Lima and Callao during the first wave of COVID-19 in Peru.

MATERIALS AND METHODS

RESULTS

Population characteristics

We included 51,503 confirmed cases of COVID-19 that were reported to the epidemiological surveillance system as hospitalized in the provinces of Lima and Callao during the first wave of the COVID-19 pandemic in Peru, who met the inclusion criteria described in Figure 1. Most of the cases were adults (46.2%) or older adults (49.2%); 60.4% were male and most were hospitalized in MINSA (39.5%) or EsSalud (40.4%) health establishments. Comorbidities were reported in 29.2% of the patients. The most frequent comorbidities were cardiovascular disease (15.6%), diabetes (11.1%), and obesity (5.14%); 7.9% were admitted to intensive care and 6.6% used mechanical ventilation. When comparing by age groups, we found that comorbidities were present in 8.8%, 21.9%, and 37.9% of the young, adult, and older adult cases, respectively (p<0.001). The prevalence of comorbidities increased in relation to the age groups (p<0.050), with the exception of obesity, asthma and immunodeficiencies, which were more frequent among the adult population. Older adults died more frequently (63.7%) compared to adults (27.1%) and young people (8.5%, p<0.001). The frequency of ICU admission and use of mechanical ventilation also increased with age (Table 1).

Figure 1 Flow chart of study participants. 

Table 1 General and clinical characteristics of patients with confirmed COVID-19 who were hospitalized in health facilities in Lima, Peru. March to October 2020. 

Factors	Total N=51,503	Age groups			p-value a
		Young (18-29)	Adults (30-59)	Older adults (≥60)
		n=2366 (4.6%)	n=23,781 (46.2%)	n=25,356 (49.2%)
	n (%)	n (%)	n (%)	n (%)
Sex					<0.001
Male	31,104 (60.4)	939 (39.7)	15,099 (63.5)	15,066 (59.4)
Female	20,399 (39.6)	1427 (60.3)	8682 (36.5)	10,290 (40.6)
Healthcare worker					<0.001
No	46,601 (90.5)	2132 (90.1)	21,144 (88.9)	23,325 (92.0)
Yes	4902 (9.5)	234 (9.9)	2637 (11.1)	2031 (8.0)
Comorbidities	15,026 (29.2)	208 (8.8)	5219 (21.9)	9599 (37.9)	<0.001
Obesity	2649 (5.1)	95 (4.0)	1570 (6.6)	984 (3.9)	<0.001
Diabetes	5737 (11.1)	30 (1.3)	1944 (8.2)	3763 (14.8)	<0.001
Cardiovascular disease	8059 (15.6)	26 (1.1)	1814 (7.6)	6219 (24.5)	<0.001
Chronic neurological disease	536 (1.0)	12 (0.5)	138 (0.6)	386 (1.5)	<0.001
Kidney disease	1144 (2.2)	19 (0.8)	324 (1.4)	801 (3.2)	<0.001
Chronic pulmonary disease	847 (1.6)	16 (0.7)	244 (1.03)	587 (2.3)	<0.001
Asthma	637 (1.2)	31 (1.3)	351 (1.5)	255 (1.0)	0.001
Liver disease	279 (0.5)	6 (0.3)	89 (0.4)	184 (0.7)	<0.001
Immunodeficiency	157 (0.3)	8 (0.3)	98 (0.4)	51 (0.2)	0.004
Cancer	757 (1.5)	15 (0.6)	243 (1.0)	499 (2.0)	<0.001
Type of health establishment					<0.001
MINSA	20,353 (39.5)	1471 (62.2)	9584 (40.3)	9298 (36.7)
EsSalud	20,830 (40.4)	454 (19.2)	8260 (34.7)	12,116 (47.8)
FFAA/PNP	3368 (6.6)	122 (5.1)	1649 (7.0)	1597 (6.3)
Private	6952 (13.5)	319 (13.5)	4288 (18.0)	2345 (9.2)
Admission to ICU	3403 (6.6)	58 (2.5)	1748 (7.4)	1597 (6.3)	<0.001
Use of mechanical ventilation	4073 (7.9)	83 (3.5)	2152 (9.1)	1838 (7.2)	<0.001
Infection period					<0.001
March/April, 2020	5911 (11.5)	204 (8.6)	3072 (12.9)	2635 (10.4)
June/July, 2020	19,580 (38.0)	899 (38.0)	9033 (38.0)	9648 (38.0)
August/September, 2020	19,027 (36.9)	816 (34.5)	8688 (36.5)	9523 (37.6)
October/November, 2020	6985 (13.6)	447 (18.9)	2988 (12.6)	3550 (14.0)
Deceased	22,787 (44.2)	200 (8.5)	6445 (27.1)	16,142 (63.7)	<0.001

^a p-value calculated with the chi-square test.

MINSA: Ministry of Health; EsSalud: Peruvian Social Health Insurance; FFAA/PNP: Armed Forces and National Police; ICU: intensive care unit.

DISCUSSION

In this study, we analyzed data from adult patients with COVID-19 who were hospitalized during the first wave of the pandemic in Lima, Peru. We found that the frequency of comorbidities and mortality increased with age. Chronic neurological disease, kidney disease, liver disease, and cancer were associated with mortality, regardless of the age group. The risk of mortality associated with comorbidities was higher in young adults compared to adults and older adults. To our knowledge, this is the first study to assess comorbidities associated with mortality in different age groups. Previous studies in Peru have reported that oxygen saturation on admission ^6,13, being over 65 years of age, lactate dehydrogenase greater than 720 U/L ¹³ and the use of mechanical ventilation or admission to the ICU ¹⁴ were factors associated with mortality.

The mortality rate in Lima and Callao was higher compared to the world average, estimated at 15% by a systematic review ¹⁵, but similar to other Latin American countries such as Colombia (40%) ⁽¹⁶. Different factors can explain why Peru has one of the highest mortality rates in the world. A contributing factor could be the collapse of the health system due to the rapid occupation of hospitalization and critical care beds, the lack of oxygen and mechanical ventilation equipment ¹⁷ and the high rates of self-medication with antibiotics or anti-inflammatories among the general population, which was estimated to be around 39% among the residents of Lima ¹⁸.

Patients older than 59 years had a mortality rate 20-times higher than those aged 18 to 29 years. Young adults had a mortality rate similar to what was reported by a study in the United States ¹⁹. Older adults had higher mortality rates compared to other high-income countries (35.5%) ²⁰, but similar to studies conducted in Latin American countries such as Brazil (64%) ²¹ and Mexico (69%). ²². Age is one of the independent risk factors for mortality, identified since the beginning of the pandemic ²³. Older people have a lower functional reserve and higher levels of angiotensin-converting enzyme 2 (ACE2), which may play a key role in the multiorgan involvement caused by SARS-CoV-2 ²⁴. Interestingly, we found that the risk of mortality associated with comorbidities was higher in young patients (18-29 years) compared to older patients. Younger patients with comorbidities died three times more than young patients without comorbidities, a difference much greater than what was found in older patients. Regression models showed greater association between comorbidities and mortality in younger patients than in older patients. One potential explanation is that young patients may have more severe or complex comorbidities than older patients leading to a worse prognosis when contracting COVID-19 and suggests that young people with comorbidities may require particularly close monitoring as high-risk group.

Chronic neurological disease, kidney disease, liver disease, and cancer were associated with mortality, regardless of age group. This finding is consistent with previous research. For example, a study in Spain found that patients with pre-existing neurological comorbidities were 1.76 times more likely to die, regardless of bed occupancy or the type of treatment ²⁵. This could be explained by the baseline health status of these patients; patients with chronic neurological disease have greater frailty and less reserve than people without chronic neurological disease. Neurological manifestations during acute illness have also been associated with a worse prognosis ²⁶. A systematic review showed that patients with chronic kidney disease are seven times more likely to die than patients without pre-existing disease ²⁷. Patients with kidney disease are in a proinflammatory state and have functional defects in innate and acquired immune cells, which increases vulnerability to infection and also worsens the prognosis ²⁸. Several studies have also shown that patients with chronic kidney disease are at increased risk of pneumonia and severe pneumonia ²⁹. Liver disease has also been associated with severity and mortality ³⁰. Obesity was also a risk factor for the group of patients over 30 years of age, which is consistent with a meta-analysis that reported that obese patients had up to four times more mortality ³¹. We found no association regarding cases between 18 and 29 years of age. We did not find an association between asthma and an increased risk of mortality. This result also agrees with previous articles. The WHO conducted a systematic review that concluded that the role of asthma as a risk factor for death from COVID-19 remains unclear ³². Another review found that the risk of infection was lower in people with asthma compared to non-asthmatics, but found no difference in terms of hospitalization, intensive care admission, ventilator use, or mortality ³³.

Our study has some limitations. First, this is a retrospective analysis of secondary data (mainly from the epidemiological surveillance system) that was not designed to estimate risk factors. For this reason, we could not include as many clinical details as an electronic medical record would. We found a lower prevalence of obesity ³⁴, chronic obstructive pulmonary disease ³⁵ and kidney disease ³⁶ than studies with specialized tests, which could be due to the lack of standardized epidemiological definitions of comorbidities. We were also unable to explore the severity of comorbidities, which may modify the effect on mortality. Our findings should be cautiously applied to other populations due to the unique chaotic situation experienced during the first wave of the pandemic in Peru, which may not reflect the reality of all hospitalized COVID-19 patients. We do not have data on variables such as oxygen saturation on admission or the treatment received during hospitalization, which could play an important role in the mortality rates. Some patients were diagnosed only with rapid serological tests. These tests have a lower diagnostic performance than molecular tests, so it is possible that some patients had false positives and false negatives. On the other hand, this study has the strength of analyzing a broad and representative sample of hospitalized patients. Previous studies in local settings have not explored comorbidities associated with mortality, so our results complement the study of COVID-19 in Peru. Furthermore, this is the first study to evaluate associated comorbidities by age group. Our multivariate analysis considered possible confounding factors, such as hospital ICU bed occupancy, type of health facility, and time from symptom onset to hospitalization.

In conclusion, in this retrospective cohort of hospitalized patients with COVID-19, we found evidence that chronic neurological disease, kidney disease, liver disease, and cancer were comorbidities associated with mortality regardless of age group. Furthermore, despite the fact that patients older than 60 years had higher mortality compared with younger patients, the risk of mortality associated with comorbidities was higher in young adults.