Chile has been one of the most affected countries by the spread of SARS-Cov-2 worldwide, and at the time of writing still struggling to contain the first wave of the Covid-19 pandemic. We report the first cohort of patients with Covid-19 in Chile and one of few in Latin America and other developing regions. The 381 patients of our cohort encompass all patients diagnosed at our institution during the first month of the pandemic and represent a significant proportion of all notified cases in Chile during the study period (n = 4,161). The cohort mirrored the beginning of the epidemic curve (first four weeks), when a large proportion (~ 65%) of patients remained able to identify a risk of exposure to SARS-CoV-2; thus, many subjects attended the hospital despite having minor symptoms to receive advice and obtain a diagnosis. Importantly, in Chile, summer vacations go from December to the first week of March, so despite frontiers closing on March 16 (only 13 days after the first case), many cases were brought into the country by returning travelers. Indeed, 47 (12.3%) of patients in our cohort had recently visited what was considered at the time a high-risk country.
A high proportion of patients in our cohort had a mild presentation, with only 18 (4.7%) out of 381 requiring ICU care, consistent with prior studies during early phases of the Covid-19 outbreak11 Interestingly, only 3 patients died during the hospitalization, representing a 3.4% of all patients requiring admission and 0.7% of the overall cohort. An in-hospital mortality rate of 3.4% is strikingly lower compared to previous large reports from Wuhan (28%), the New York Area (21%) and other European countries.12–15 This difference could be explained by a lower threshold for admission in our cohort at a time when the healthcare system was not yet overloaded and bed capacity was high. However, an in-hospital mortality of 22% reported from Germany at a time when the healthcare capacity was not burdened argues against this as the sole explanation.14 Also, patients in our cohort were younger (median age 49) compared to the New York, Wuhan and German cohorts (median ages 63, 56 and 72 respectively). Age has been consistently associated with disease severity and outcomes 12,16, hence, it is likely a contributing factor in the lower mortality rates observed in our cohort. Furthermore, previous cohorts 14,15 excluded a large proportion of patients who remained hospitalized at the time of study closure, biasing results towards an increased mortality rate due to a higher inclusion of patients who died early in the course of admission. Finally, it is important to highlight that these outcomes reflect the results of a healthcare institution serving a higher-income section of the population, and may vary from those observed in the lower resource public health system.
The cohort presented here is mostly Hispanic, an ethnic population generally underrepresented in medical research.17 Data from the United Kingdom and USA has shown an increased risk of severe COVID-19 among ethnic minorities.18–20 The low fatality and ICU rate of our cohort suggests that the ethnicity issue might rather be a problem of socioeconomic disparity. Studies appropriately representing minority populations are sorely needed. Indeed, failing to include an ethnically representative population leads to results that may not apply to these groups, increasing the health inequality. In Chile and other Latin American countries, future comparative studies of different socioeconomic groups will help to understand the influences of genetic factors and social inequality on the dynamics and outcomes of Covid-19.
As reported elsewhere,21 higher CRP levels were associated with increased odds of need for ICU care or in-hospital death. Further, our data suggest that elevated CRP levels in the first 24 hours of admission were a biomarker for severe clinical presentation of Covid-19. CRP is an acute phase protein released mainly in response to interleukin-6 (IL-6), a cytokine that has also been associated with disease severity in Covid-19.12 Higher CRP levels are likely associated with a higher inflammatory response, which may correspond with increased tissue damage. CRP levels are widely available and generally cheaper than measuring IL-6 levels and therefore may represent an interesting biomarker to investigate in future studies. Increased BMI was also associated with severe disease. Several theories have been raised to explain this association, which was described before in other cohorts22, including overactivated inflammation and immune response, decreased chest expansion, and increased expression of ACE 2, among others.22–23 Although the mechanisms are beyond the scope of this study, BMI seems to be a useful predictor of Covid-19 severity and therefore obese patients should be considered a high-risk population. Finally, although the SaTO2/FiO2 index on admission was not independently associated with our main outcome (p = 0.051), it was very close to our pre-established level of significance. These data, along with a high biological plausibility suggests this index is worth exploring as a marker for the development of severe Covid-19 disease in future studies.
The role of other biomarkers previously identified as predictors of in-hospital mortality or ICU need were not confirmed in our cohort. These findings could be explained due to the limited number of patients included in our series along with the low frequency of occurrence of our primary outcomes (i.e. ICU admission and/or in-hospital mortality). In addition, other relevant limitations of our study include that it is a single center effort and its observational nature. Due to the latter, we did not explore treatment effects given our limited ability to appropriately correct for potential confounders. However, our data were prospectively collected with high quality standards and provide one of the few studies contributing information from developing areas of the world, in this case South America. As mentioned above, the data of this cohort mainly represent the initially affected high-income population of Chile and a time of the pandemic were the healthcare system was not yet overwhelmed. Therefore, future studies analyzing the general population attending to a wider range of hospital centers and reflecting a systemic stress created by the large number of patients infected with SARS-CoV-2 will be important to help understand the possible influence of social and health disparities, and of the system overload in the outcomes of Covid-19 patients.