Investigating tools to predict the outcome of COVID-19 positive older adults plays a pivoting role in the treatment, safety, and prognosis predictions of critically ill individuals. The present study investigates the usefulness of the CCI to predict mortality in older patients with COVID-19 pneumonia and non-COVID-19 pneumonia.
A CCI score below 3 was associated with death in patients with COVID-19 of 60 years and above, the overall performance of the scale to predict death was 0.71. There were no differences in the hazard ratio between mild, medium, and high-risk patients when patients were categorized with the original CCI guidelines. However, when patients were sub-grouped into ≤ 3 and ≥ 4 CCI, a hazard ratio was increased in the ≤ 3 group. Age, BMI, dyspnea and SO2/FiO2 were associated with COVId-19 pneumonia whereas BMI, RF and SO2/FiO2 and Charlson comorbidity Index were associated with death.
The usefulness of CCI to predict risk of death has been investigated in the general population and it has been suggested for risk stratification of hospitalized COVID-19 positive patients (Tuty Kuswardhani et al. 2020; Barış et al. 2022). In a meta-analysis a worst prognosis was observed in patients with score of 1–2 compared to a score of 0 (Tuty Kuswardhani et al. 2020). Another study reported a sensitivity of 87.2% to predict mortality in patients with a CCI score of 4 and above, also in the general population (S and A 2022).
In older patients, a case-control study performed in China reports a median of 5 (IQR 4–6) (Zhang et al. 2021) compared to our study the median of the total studied population was 4 (3–5), the median for surviving patients was 3 (IQR 2–4) and the median for deceased patients was 4 (IQR 3–5). In general, we do report a lower CCI score compared to other studies.
There are very few studies regarding CCI in older patients with COVID-19. However, in a study of 224 individuals over 65 years of age, with COVID-19 and who required hospitalization, logistical regression analysis have shown that CCI score is associated with mortality, with a median CCI score of 6 (IQR 5–7) for deceased patients and a median CCI score of 4 (IQR 3–6) for survivors (Ioannou et al. 2022).
We demonstrate that when comparing COVID-19 pneumonia patients with non-COVID-19 pneumonia patients a significant association with mortality was observed in COVID-19 pneumonia patients with a CCI score of less than 3, rather than the moderate or high-risk category, which was originally described by Charlson and colleagues in 1987 (Charlson et al. 1987a). Other studies have also categorized older patients in < 3 and ≥ 3 CCI score (Hsu et al. 2021), and it has been reported in that in certain cases a CCI of ≥ 2 in a risk factor for death (Cao et al. 2021). A study in India that included 50,668 patients ≥ 60 years of age also categorized patients as 0, 1 and ≥ 2 (32).
In general, there were more comorbid patients in the COVID-19 positive group compared to the COVID-19 negative group. Individual comorbidities were not significantly associated with pneumonia nor with outcome and 50.6% of the studied population presented more than one comorbidity. Mexico is one of the countries with the highest incidence of diabetes with 24.9% reported in 2018 for people over 70 years and 25.8% for those between 60–69 years of age (33). In our population people with only diabetes as a single comorbidity was 6.6% however, diabetes is often presented with other comorbidities such as hypertension. In our population patients with both diabetes and hypertension were 144 in our population, taking this into account, the prevalence of diabetes in the studied population was 50%. Hypertension is also of the most common comorbidities in our population and taking into consideration those with 2 comorbidities, there were 241 cases with hypertension, which corresponds to 72.5%, which agrees with the literature for this age group with an expected incidence of 76.9 % (34).
One of the variables that was associated with an increased risk of COVID-19 pneumonia and death was BMI. In the studied population 23% had a BMI greater than 30. Obesity is a major public health problem in Mexico, and it has been already pointed as a risk factor for hospitalization, intensive care unit admission, invasive mechanical ventilation, and mortality in COVID-19 patients (35–37). The present article agrees by demonstrating that this is also the case in older patients. Specifically in the Mexican population from Nuevo León, a study has reported that obesity is associated with infection and an increased severity of COVID-19 (38). A review has suggested the chronic inflammation could be the potential mechanism by which obesity might be predisposing to COVID-19 infection and death (39). Chronic inflammation might cause an increase of inflammatory molecules compared to non-obese patients when infected with COVID-19 (40). Vitamin D deficiency, intestinal dysbiosis, and an increase of ACE-2 expression, which is the receptor of SARS-CoV-2, the virus that causes COVID-19 (39).
CCI is one the widest cited comorbidity indexes, its inter-rater reliability, concurrent validity, sensitivity among other parameters have been tested is many articles. The original article has been cited 36,741 times according to Scopus (November 3, 2023) (41). However, this index was not designed for in-hospital mortality and although there is no gold standard for comorbidity index, it has been widely used for in-hospital mortality and it has been proved a good predictor. For instance, de Miguel-Diez (2018) used CCI to assess in-hospital mortality in hospitalized patients with heart failure and they found that CCI predicted in-hospital mortality (42). Another Swiss study investigated CCI in patients hospitalized with acute coronary syndrome (ACS) and found CCI to be an appropriate prognostic indicator for in-hospital mortality and 1-year outcome in ACS patients (43). In a Chinese study in 154,378 hospitalized adults between 2008 and 2012 with hyponatremia it was reported that CCI was the most important predictor or in-hospital death (44).
There are other scales, designed for in-hospital mortality such as the Elixhauser comorbidity index (45), which comprises 30 conditions including acute problems such as blood loss, collagen vascular diseases, and fluid and electrolyte disorders which is not often included in routine hospital exams in Mexico and were not available for our patients. A study performed in geriatric patients tested CCI, Elixhauser comorbidity index, geriatric index of comorbidity and Medicine Comorbidity Index and demonstrated that none of the indices is sufficient to use alone in geriatric practice (46). Therefore, the results of studies with only one scale such as the present should be taken with caution.
Other factor that was significantly associated with COVID-19 pneumonia was SO2/FiO2 ratio. SO2/FiO2 ratio of < 299.9 was a protective factor against COVID-19 pneumonia or in another words, people with COVID-19 pneumonia had better SO2/FiO2 ratio compared to those with non- COVID-19 pneumonia. Several drawbacks have been reported when using SO2/FiO2 ratio including anemia, excessive motion, low perfusion, skin color, among others (47). In pneumonia regression analysis, survivors and non-survivors are included and SO2/FiO2 has previously been associated with increased mortality in COVID-19 pneumonia patients (48). The latter agreeing with our study.
We recognize that our study has some limitations including the low number of samples, which only come from a general hospital that was reconverted to a COVID-19 hospital during the pandemic. Furthermore, given that this is a geriatric population it is possible that some comorbidities are underdiagnosed. Results could vary depending on the population; therefore, more studies should be performed in a larger cohort and in different populations.
In conclusion, according to our analysis, CCI needs to be adjusted in aged patients with COVID-19 as it might be that a score < 3 could be indicative of an increased mortality, and CCI is insufficient to use alone in geriatric patients. Other factors should be taken into consideration of mortality prediction, such as BMI, respiratory frequency and SO2/FiO2. The findings of this study could be validated in geriatric patients with COVID-19 in other populations from Mexico or other countries.