key: cord-0960473-ow53bzqn
authors: Espiritu, Adrian I.; Reyes, Nikolai Gil D.; Leochico, Carl Froilan D.; Sy, Marie Charmaine C.; Anlacan, Veeda Michelle M.; Jamora, Roland Dominic G.; Macalintal, Corina Maria Socorro A.; Robles, Joanne B.; Cataniag, Paulo L.; Flores, Manolo Kristoffer C.; Tangcuangco-Trinidad, Noreen Jhoanna C.; Juango, Dan Neftalie A.; Paas, Giuliani Renz G.; Chua, Audrey Marie U.; Estrada, Valmarie S.; Mejia, Philip Rico P.; Reyes, Therese Franz B.; Cañete, Maria Teresa A.; Zapata, Ferdinand Renfred A.; Castillo, Franko Eugenio B.; Esagunde, Romulo U.; Gantioque, Jean B.; Abbariao, Maritoni C.; Acebuque, Geramie M.; Corral, Evram V.; Escasura, Marian Irene C.; Ong, Marissa T.; Pineda, Arnold Angelo M.; Aradani, Khassmeen D.; Catindig, Joseree-Ann S.; Cinco, Mark Timothy T.; Ramos, Mark Erving H.; Cruz, Romulus Emmanuel H.; Dantes, Marita B.; Francisco, Norberto A.; Teleg, Rosalia A.; Bellosillo, Krisverlyn B.; Delfino, Jean Paolo M.; Diesta, Cid Czarina E.; Espiritu-Picar, Rosalina B.; Gamboa, Julie Anne V.; Matute, Cara Camille M.; Padilla, Franzelle P.; Punsalan, John Joshua Q.; Collantes, Ma.Epifania V.; Que, Charmaine B.; Sampao, Hanifa A.; Sta. Maria, Maxine Camela S.; Fuentes, Marita M.; Manzano, Jennifer Justice F.; Umali, Rizza J.; Molina, Marc Conrad C.; Minerva-Ang, Hazel Claire M.; Surdilla, Arturo F.; Talabucon, Loreto; Wabe, Natasha F.; Banday, Christian Paul B.; Pangandaman, Nehar A.; Wasil, Avery Gail C.; Inocian, Elrey P.; Vatanagul, Jarungchai Anton S.; Apor, Almira Doreen Abigail O.; Dioquino, Carissa Paz C.; Villanueva, Emilio Q.; Dela Cruz, Prinz Andrew M.; Yumul, Maricar P.; Manuel, Maria Victoria G.; Pajantoy, Al Inde John A.; Roque, Josephine Cecilia V.; Yambao, Paul Emmanuel L.; Carandang-Concepcion, Ma. Alma E.; Desquitado, Ma.Caridad V.; Julao, Carl Kevin L.; Bornales, Dante P.; Maylem, Generaldo D.; Cuntapay, Mark Joseph F.; Lao-Reyes, Annabelle Y.; Manlegro, Nadia O.; Pelere, Dave Mar L.; Laxamana, Lina C.; Que, Diana-Lynn S.; Yu, Jeryl Ritzi T.; Martinez, Ma.Socorro C.; Matic, Alexandria E.; Perez, John Angelo S.; Constantino, Glenn Anthony A.; Olano, Aldanica R.; Quiles, Liz Edenberg P.; Roxas, Artemio A.; Soliven, Jo Ann R.; Montojo-Tamayo, Michael Dorothy Frances; Joson, Ma. Lourdes C.; Evangelista, Jojo R.; Nuñez, Ma.Clarissa B.; Olaivar, Marietta C.; Perez, Dominique Q.; Armeña, Mark Deneb O.; Barja, Robert A.; Abejero, Joshua Emmanuel E.; Eribal, Maritzie R.; Alava, Ryndell G.; Kalbi, Muktader A.; Radja, Nasheera W.; Sali, Mohammad Elshad S.
title: Body mass index and its association with COVID-19 clinical outcomes: findings from the Philippine CORONA study
date: 2022-03-31
journal: Clin Nutr ESPEN
DOI: 10.1016/j.clnesp.2022.03.013
sha: ad8281a21fb335c6f8d6e9f79235eab74893d272
doc_id: 960473
cord_uid: ow53bzqn

Background and Aims To explore the association between body mass index (BMI) and adverse outcomes in a large cohort of patients with coronavirus disease 2019 (COVID-19). Methods This is a secondary analysis of The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms study, a 37-site, nationwide, multicenter, retrospective cohort study that investigated the clinical and neurological outcomes of adult patients with confirmed COVID-19 admitted from February to December 15, 2020. We analyzed data from patients with available BMI information during admission, along with other relevant details including age, sex, smoking status, clinical characteristics (specific and cumulative number of comorbid conditions, neurologic history and manifestations, non-neurologic presenting symptoms, treatment/s received), and in-hospital outcomes. Results A total of 4,463 patients with available BMI and outcome data were included in this secondary analysis. A total of 790 (17.7%) and 710 (15.9%) had the primary outcome of in-hospital mortality and need for invasive mechanical ventilation (IMV) over a median hospital stay of 13 (interquartile range: 8) days. Multivariable Cox proportional analysis found no significant association between World Health Organization BMI groups and these outcomes, although sensitivity analysis using lower Asia-Pacific cutoffs show a significant association between obesity and in-hospital mortality risk (hazard ratio 1.35; 95% CI, 1.07-1.41; P = 0.012). Significant age interaction contributed to nonuniform risks observed for IMV requirement across BMI groups. Multivariable binary logistic regression analysis showed that being underweight was an independent predictor of prolonged IMV requirement regardless of BMI criteria used (P for both criteria < 0.01), whereas obesity was found to correlate with the need for intensive care unit admission using Asia-Pacific cutoffs (odds ratio [OR] 1.28; 95% CI, 1.03 – 1.59; P = 0.029). Adjusted and sensitivity analyses demonstrated significant association between any BMI abnormality and odds of severe/critical COVID-19 (P < 0.05). Regardless of BMI classification system used, obese patients with concomitant acute neurologic presentation or diagnosis during their COVID-19 admission were shown to have lower odds of neurologic recovery (P for both criteria < 0.05). Conclusions We found BMI abnormalities to be associated with several adverse clinical and neurologic outcomes, although such associations may be more evident with the use of race-specific BMI criteria.

ABSTRACT Background and Aims: To explore the association between body mass index (BMI) and adverse outcomes in a large cohort of patients with coronavirus disease 2019 (COVID- 19) .

Methods: This is a secondary analysis of The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms study, a 37-site, nationwide, multicenter, retrospective cohort study that investigated the clinical and neurological outcomes of adult patients with confirmed COVID-19 admitted from February to December 15, 2020. We analyzed data from patients with available BMI information during admission, along with other relevant details including age, sex, smoking status, clinical characteristics (specific and cumulative number of comorbid conditions, neurologic history and manifestations, nonneurologic presenting symptoms, treatment/s received), and in-hospital outcomes.

Results: A total of 4,463 patients with available BMI and outcome data were included in this secondary analysis. A total of 790 (17.7%) and 710 (15.9%) had the primary outcome of inhospital mortality and need for invasive mechanical ventilation (IMV) over a median hospital stay of 13 (interquartile range: 8) days. Multivariable Cox proportional analysis found no significant association between World Health Organization BMI groups and these outcomes, although sensitivity analysis using lower Asia-Pacific cutoffs show a significant association between obesity and in-hospital mortality risk (hazard ratio 1.35; 95% CI, 1.07-1.41; P = 0.012).

Significant age interaction contributed to nonuniform risks observed for IMV requirement across BMI groups. Multivariable binary logistic regression analysis showed that being underweight was an independent predictor of prolonged IMV requirement regardless of BMI criteria used (P for both criteria < 0.01), whereas obesity was found to correlate with the need for intensive care unit admission using Asia-Pacific cutoffs (odds ratio [ More than a year since its declaration as a pandemic, coronavirus disease 2019 caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to pose significant threats to public health worldwide [1] . As of August 6, 2021, the Philippines, a developing Southeast Asian country with an estimated population of 110 million people, has documented a total of 1,638,345 laboratory-confirmed cases, with 74,297 active infections and 28,673 deaths [2] . As local and global cases continue to rise, so do their negative impact on the country's strained healthcare system [3] . As such, the determination of clinical prognostic factors for patient risk stratification, management algorithms, and resource allocation strategies is needed [4] .

Abnormal body mass index (BMI) has been proposed as an independent prognostic factor in COVID-19, although its exact relationship and effect size on clinical outcomes remain unclear.

Some reports demonstrate a significant association between BMI abnormalities and poor outcomes, others have not found such a correlation [5] [6] [7] [8] [9] [10] [11] . In studies that included both underweight and obese patients, a J-shaped association was observed in terms of risk of intubation, death, or a composite of these outcomes [12] [13] [14] . The existence of an obesity survival paradox, a phenomenon wherein alterations in fat accumulation and adipose microenvironment exert protective effects in critically ill patients, in COVID-19 remains speculative [5, 12, 15] .

Furthermore, the applicability of the observed findings in other parts of the world, specifically in countries that face the double burden of malnutrition, is still unknown due to limited evidence [16] . We hypothesized that abnormalities at the two ends of the BMI spectrum would significantly affect clinical and neurologic outcomes of COVID-19 patients. To test this J o u r n a l P r e -p r o o f hypothesis and address the knowledge gaps, we performed a secondary analysis of data from The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (Philippine CORONA Study) to explore the association between BMI and adverse outcomes in a large cohort of patients hospitalized for COVID-19 [17] .

The Philippine CORONA Study was a nationwide, multicenter, retrospective cohort study that investigated the clinical and neurologic outcomes of adult patients with confirmed COVID-19 and were consecutively admitted in any of the 37 participating hospitals across the country between February 1 to December 15, 2020 [17] . The study obtained approval from the respective research ethics boards of all participating sites and was registered in ClinicalTrials.gov (NCT04386083). Specific details about the research design, patient enrollment, and data collection procedures were discussed in the published protocol [18] .

For this study, we analyzed data from patients with available BMI information during admission, along with other relevant details including age, sex, smoking status, clinical characteristics (specific and cumulative number of comorbid conditions, neurologic history and manifestations, non-neurologic presenting symptoms, treatment/s received), and in-hospital outcomes.

We operationalized BMI, calculated as weight in kilograms divided by the square of height in meters (kg/m 2 ), as our primary exposure. Weight and height measurements were recorded upon J o u r n a l P r e -p r o o f hospital admission. We analyzed BMI as a categorical variable using the World Health Organization (WHO) criteria: underweight (BMI < 18.5 kg/m 2 ), normal (BMI 18.5 -24.9 kg/m 2 ), overweight (BMI 25 -29.9 kg/m 2 ), and obese (BMI ≥ 30 kg/m 2 ) [19] . Patients with missing or implausible BMI data were excluded from the analyses.

Our primary outcomes of interest were in-hospital mortality and need for invasive mechanical ventilation (IMV). We also explored the association between BMI and several dichotomized secondary endpoints including COVID-19 severity at nadir (mild/moderate versus severe/critical), intensive care unit (ICU) admission (admitted versus not admitted), and lengths of IMV dependence (<14 versus ≥14 days), ICU admission (≤7 versus > 7 days), and overall hospital stay (≤14 versus > 14 days). We also explored the association of BMI with neurologic outcomes (full/partial versus no neurologic improvement) among patients who had any neurologic symptom or diagnosis on admission.

The baseline patient characteristics across the prespecified BMI criteria was summarized using descriptive statistics. Continuous variables were presented as median (interquartile range, IQR), and categorical variables as frequencies and proportions. Unadjusted analysis of between-group differences was done using one-way ANOVA or Kruskal-Wallis test for continuous variables, and chi-square or Fisher exact tests for categorical variables. We applied Cox proportional hazards and binary logistic regression models in the analysis of our primary and secondary endpoints, respectively. Multivariable regression models with normal BMI category as reference J o u r n a l P r e -p r o o f were constructed for both primary and secondary outcomes after adjusting for a priori defined covariates namely, age, sex, smoking status, hypertension, diabetes, chronic respiratory disease, chronic cardiac disease, chronic kidney disease, chronic neurologic disease, and malignancy [13, 20] . Effect modification by age and sex was evaluated by stratified analysis with likelihood ratio test utilizing full and reduced models with and without the interaction terms, respectively.

Kaplan-Meier plots and log-rank tests were also done to examine the association between BMI and time-to-event data for mortality and need for IMV. Lastly, we conducted a sensitivity analysis to determine differences in estimates between WHO international BMI criteria and the Asia-Pacific classification, with the latter having the following trigger points based on risk for adverse health outcomes: underweight (<18.5 kg/m 2 ), normal (18.5 -22.9 kg/m 2 ), overweight/increased risk (23 -27.5 kg/m 2 ), and obese/higher high risk (≥ 27.5 kg/m 2 ) [19] .

Given the exploratory nature of this study, no imputations were made for missing data.

All tests were two-tailed, and we set P < 0.05 as the threshold for statistical significance. All analyses were carried out in Stata Version 15.1 (StataCorp LLC, TX, USA).

Among the 10,881 patients in the Philippine CORONA Study, 4,463 (41%) had available BMI and outcome data and were included in the full analytic cohort (Supplementary Figure 1) .

Baseline data are summarized in Table 1 . The median BMI was 25.0 kg/m 2 with the following distribution per category: underweight (3.4%), normal (47.0%), overweight (32.8%), and obese (16.8%). Majority of patients were <60 years of age with a median age of 54 years (IQR: 28).

Within the cohort, there were more males (P < 0.001) and nonsmokers (P = 0.023) across the BMI strata. Hypertension, diabetes, and chronic respiratory disease displayed a direct trend, whereas chronic kidney disease and HIV/AIDS showed an inverse trend in relation to BMI (P < 0.05). On admission, 76.8% presented with at least one non-neurologic symptom, with fever, cough, and dyspnea being more frequently observed among patients with higher BMI classes (P < 0.05) (Supplementary Table 1 ). In terms of neurologic profile, the proportions of patients with chronic, as well as acute neurologic symptom or diagnosis on admission, appeared to decrease with higher BMI (P < 0.05). We observed significantly inhomogeneous proportions of treatment administered, with overweight and obese patients having received glucocorticoids, tocilizumab, antiviral, and antibacterial medications more frequently compared to other BMI groups (P < 0.05).

Within the study period, 790 (17.7%) patients were intubated and 710 (15.9%) died over a median hospital stay of 13 days (IQR, 8 days; P = 0.647), the proportions of which did not differ across BMI strata (P = 0.974 and 0.858 for IMV requirement and in-hospital mortality, respectively) ( Table 2 ). In the multivariable Cox model, adjusted analysis showed no differences in estimated risks for in-hospital mortality and IMV requirement across all BMI groups ( Figures   1A and 1B) . These findings did not vary by age group nor sex (Supplementary Tables 2 and   3 ). Correspondingly, the time-to-mortality and -intubation data showed no significant differences across BMI categories ( Figures 1C and 1D ).

Among those who were intubated, however, a higher proportion of underweight patients had longer IMV dependence compared to other BMI groups (P = 0.011) with a median duration of 20 days (IQR, 15 days; P = 0.025) ( Table 2) . This observation remained consistent after adjusting for multiple covariates (OR, 4.98; 95% CI, 1.80 -13.78; P = 0.002) ( Table 3) .

Unadjusted and adjusted analyses also revealed a significant, J-shaped association between BMI abnormalities and COVID-19 severity (unadjusted P = 0.012), with underweight (OR, 1.48; 95% CI, 1.03 -2.14; P = 0.035) and obese (OR, 1.46; 95% CI, 1.22 -1.76; P < 0.001) patients showing the highest, and overweight patients demonstrating a modest, but statistically significant, odds of developing severe/critical COVID-19 at nadir (OR, 1.19; 95% CI, 1.02 -1.38; P = 0.024) (Tables 2 and 3 ). In contrast, we did not find BMI category, using WHO classification, to be independently associated with the other secondary endpoints in both unadjusted and adjusted analyses (Tables 2 and 3 ). In the subgroup of COVID-19 patients who had a neurologic presentation or diagnosis on admission, 784 (82.4%) had available data for analysis of neurologic outcomes. Whereas between-group comparison failed to reveal any significant differences across BMI strata, the adjusted analysis demonstrated decreased odds of full or partial neurologic recovery on discharge among obese, COVID-19-infected patients (OR, 0.48; 95% CI, 0.25 -0.90; P = 0.023) (Tables 2 and 3 ). No significant interactions by age group or sex were found for these secondary endpoints (Supplementary Tables 2 and 3 ).

The results of the sensitivity analyses are shown in Table 4 . Comparing the two BMI criteria, similar trends were seen for primary endpoints, although a significant difference in effect size (>10%) was detected for in-hospital mortality risk. While increasing weight appeared to correlate J o u r n a l P r e -p r o o f directly with the said risk, statistical significance was only reached for those classified as obese using Asia-Pacific cutoffs (P = 0.012). Stratification by age group showed significant differences in risk estimates for IMV requirement between the two criteria, with younger (18-59 years) overweight patients having a significantly reduced risk (HR, 0.69; 95% CI, 0.51 -0.94; P = 0.018), and older (≥60 y) overweight and obese patients having a significantly greater risk of IMV requirement based on Asia-Pacific cutoff points (HR, 1.25; 95% CI, 1.01 -1.57; P = 0.039 and HR, 1.32; 95% CI, 1.04 -1.69; P = 0.025 for overweight and obese strata, respectively).

Obesity, as defined in the Asia-Pacific criteria, was also shown to be independently associated with the need for ICU admission (OR, 1.28; 95% CI, 1.03 -1.59; P = 0.029). Similar trends in odds estimates were observed for duration of IMV dependence, COVID-19 severity at nadir, and lengths of ICU and hospital stay using both BMI criteria. Lastly, although significant differences in effect sizes were detected, the statistically significant association between BMI and neurologic outcomes remained consistent even with the use of Asia-Pacific cutoff points. No significant effect-measure interactions were found after stratifying for sex.

This nationwide observational study with the largest cohort of Asian patients to date demonstrated the association, or lack thereof, of BMI abnormalities with several clinical and neurologic outcomes of patients hospitalized for COVID-19.

Compared to available nutritional data, our cohort showed a lower proportion of underweight and higher proportions of overweight and obese patients. Such differences in prevalence estimates may be expected in the context of rapidly changing patterns in diet, physical activity J o u r n a l P r e -p r o o f and mobility, food systems, and economic status [16, [21] [22] [23] . In terms of baseline clinical findings, we observed higher proportions of concomitant non-communicable diseases among overweight and obese patients admitted for COVID-19. Chronic respiratory disease and dyspnea on admission were more frequently found in these subgroups, expanding prior observations showing an association between excess weight and altered respiratory biomechanics and function [8, 9] . We also found higher proportions of concurrent HIV/AIDS and chronic kidney disease among underweight individuals, which may relate to the negative downstream effects of these conditions on muscle mass and weight [24, 25] . Additional longitudinal assessments are needed to quantify the degree to which COVID-19 infection impacts measures of body composition and energy state.

We demonstrated an apparent nonuniform risks and time-to-mortality and intubation depending on BMI criteria used. While no association was found in terms of WHO BMI criteria, the use of lower cutoff points in the Asia-Pacific classification system showed obesity to be an independent predictor of the risks for mortality, intubation, and ICU admission, although this did not seem to significantly affect the durations of ICU and hospital stay. This finding was in agreement with past observations [5, 6, 8, 9, 12] . The heightened risk for adverse outcomes may stem from the interplay of multiple mechanisms including, but not limited to, immune and hormonal dysregulation, endothelial dysfunction, impaired lung biomechanics, and the chronic, proinflammatory state associated with increased body weight and adiposity [4, 8, 9, 12] . Our data also highlighted the potential utility and sensitivity of race-specific BMI criteria, which consider ethnic differences in body composition and adiposity, in estimating COVID-19 prognosis and informing discussions pertaining to resource allocation and advanced care planning [9, 19] .

Consistent with another report, we found age to be a significant factor in the differential risk of IMV requirement observed across BMI strata [7] . Our results demonstrated that overweight and obesity, classified using race-specific criteria, conferred a greater risk of intubation among elderly individuals, whereas being overweight appeared to reduce this risk among those < 60 years of age. That the latter was observed without a concomitant elevation in the mortality risk points to the possible existence of a survival paradox in COVID-19 postulated in prior studies [5, 13, 15] . The results of our analysis, however, suggested that the reduction of risk may only occur at a certain range of excess weight and its occurrence may be restricted to younger patients. Further studies are warranted to determine the BMI cutoff point at which the protective benefit of excess weight declines and becomes a risk factor for intubation and expound on the mechanisms that drive this shift.

Our data also demonstrated that BMI abnormalities confer a significant risk for the development of severe/critical COVID-19 at nadir regardless of age, sex or BMI criteria used, with extremes of BMI (i.e., underweight and obesity) showing a more striking association compared to normal and overweight. We found it interesting that higher odds of severe/critical illness among younger, overweight patients arose in the background of a reduced risk of intubation and a nonsignificant risk of in-hospital mortality, which altogether support the age-dependent survival paradox described earlier. The direct correlation observed between BMI and COVID-19 severity was independent of cardiometabolic and other conditions related to excess weight, a finding consistent across observational reports, two of which involved primarily Asian cohorts [7, 8, 26, 27] . In contrast to prior observations, underweight stratification appeared to be a strong, J o u r n a l P r e -p r o o f independent risk factor not only for severe COVID-19, but also for prolonged IMV requirement [7, 9, 14] . The relatively higher proportion of underweight patients in our cohort may partially explain this disparity, and possibly provides a more precise estimate of the impact of low BMI on these outcomes. Our findings further emphasized the importance of giving comparable attention to underweight patients in terms of prevention, hospital triage, and treatment strategies due to their significant risk for COVID-19 morbidity. One study linked this association to the underlying frailty and altered immune responses associated with being underweight [12] .

Another report also found a significant, albeit tenuous, correlation between low BMI and decreased diaphragmatic thickness, an emerging predictive marker of prolonged IMV requirement among critically ill patients [28] . Future studies employing more accurate measurements of adiposity, fat-free muscle mass, pulmonary function, and inflammatory response may help elucidate the complex relationship between BMI and respiratory complications of severe COVID-19.

Although neurologic involvement in COVID-19 has been documented in previous studies, none have addressed the contribution of BMI abnormalities on neurologic outcomes [29, 30] . Our data showed that obesity may be an independent predictor of poor neurologic recovery among COVID-19 patients with an acute neurologic presentation or condition on admission. This association remained robust even after performing effect modification and sensitivity analyses.

The underlying mechanisms for this finding are still unknown. It is theoretically plausible that the downstream effects of obesity described earlier overlap or act synergistically with the direct and immune-mediated neurologic injury elicited by SARS-CoV-2, although our present data cannot confirm this hypothesis [29] . The determination of exact mechanisms by which obesity contributes to the systemic and neuroinflammatory effects of COVID-19, and the magnitude by which this interaction ultimately affects neurologic and overall prognosis requires continued investigation.

This study has several limitations. As this is a secondary analysis of published data, our findings should be construed as exploratory and any significant or nonsignificant association detected must be confirmed in large-scale, prospective studies to generate clinically meaningful conclusions [17] . Other study limitations include the retrospective design, the large amount of missing data, and the lack of accurate measurements of COVID-19 inflammatory biomarkers and viral shedding. Lastly, it should be noted that this study heavily relied on anthropometric assessment (i.e., BMI), which may not fully capture other nutritional aspects that potentially affect disease outcomes.

This large-scale study demonstrated that obesity, classified using race-specific BMI criteria, was associated with an increased risk of adverse outcomes including severe/critical COVID-19, IMV requirement, ICU admission, poor neurologic recovery, and in-hospital mortality in an Asian cohort. Although being overweight appeared to be associated with the risk for severe/critical COVID-19, this does not seem to elevate the risk of death. These findings, combined with a reduced risk of intubation seen only in the younger age group, suggest that such paradox is probably age-dependent and might only be evident within a critical range of excess weight. The threshold for, and mechanisms underlying this phenomenon merit further investigation. Due to factors such as underlying frailty, maladaptive immune responses, and altered respiratory J o u r n a l P r e -p r o o f mechanics, underweight patients may also be at risk for severe/critical COVID-19 and prolonged IMV requirement, and thus deserve comparable attention in terms of preventive and treatment strategies. Larger prospective studies with more precise nutritional assessment methods and biomarkers are needed to elucidate the complex relationship between body composition and COVID-19 outcomes.

None. J o u r n a l P r e -p r o o f

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Non-neurologic comorbidities Hypertension, n (%) Diabetes mellitus, n (%) Chronic cardiac disease a , n (%) Chronic respiratory disease b , n (%) Chronic kidney disease, n (%) Chronic liver disease

HIV/AIDS, n (%) Others, n (%)

Non-neurologic presenting symptom, n (%) Fever, n (%) Cough, n (%) Dyspnea, n (%) Sore throat, n (%) Diarrhea, n (%) Fatigue, n (%)