bims-covirf Biomed News
on COVID19 risk factors
Issue of 2020–07–12
twelve papers selected by
Catherine Rycroft, BresMed
  1. Risk Factors for Mortality among COVID-19 Patients.
  2. A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis.
  3. OpenSAFELY: factors associated with COVID-19 death in 17 million patients.
  4. Coronavirus disease (COVID-19): A systematic review and meta-analysis to evaluate the impact of various comorbidities on serious events.
  5. Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease.
  6. A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity.
  7. Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis.
  8. Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank.
  9. The impact of ethnicity on clinical outcomes in COVID-19: A systematic review.
  10. Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis.
  11. Smoking, SARS-CoV-2 and COVID-19: A review of reviews considering implications for public health policy and practice.
  12. Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study.
  1. Diabetes Res Clin Pract. 2020 Jul 02. pii: S0168-8227(20)30545-3. [Epub ahead of print] 108293
    Risk Factors for Mortality among COVID-19 Patients.
    Orwa Albitar, Rama Ballouze, Jer Ping Ooi, Siti Maisharah Sheikh Ghadzi.
       AIMS: COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data.
    METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality.
    RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients.
    CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.
    Keywords:  COVID-19; Cross-sectional; Mortality; Outcome; Risk factors
    DOI:  https://doi.org/10.1016/j.diabres.2020.108293
  2. J Infect. 2020 Jul 04. pii: S0163-4453(20)30460-6. [Epub ahead of print]
    A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis.
    Lvliang Lu, Wenyu Zhong, Ziwei Bian, Zhiming Li, Ke Zhang, Boxuan Liang, Yizhou Zhong, Manjiang Hu, Li Lin, Jun Liu, Xi Lin, Yuji Huang, Junying Jiang, Xingfen Yang, Xin Zhang, Zhenlie Huang.
       OBJECTIVE: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment.
    METHODS: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI).
    RESULTS: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients.
    CONCLUSIONS: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.
    Keywords:  COVID-19; MERS; Meta-analysis; Mortality; Risk factors; SARS
    DOI:  https://doi.org/10.1016/j.jinf.2020.07.002
  3. Nature. 2020 Jul 08.
    OpenSAFELY: factors associated with COVID-19 death in 17 million patients.
    Elizabeth J Williamson, Alex J Walker, Krishnan Bhaskaran, Seb Bacon, Chris Bates, Caroline E Morton, Helen J Curtis, Amir Mehrkar, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I McDonald, Brian MacKenna, Laurie Tomlinson, Ian J Douglas, Christopher T Rentsch, Rohini Mathur, Angel Y S Wong, Richard Grieve, David Harrison, Harriet Forbes, Anna Schultze, Richard Croker, John Parry, Frank Hester, Sam Harper, Rafael Perera, Stephen J W Evans, Liam Smeeth, Ben Goldacre.
      COVID-19 has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30-1.69 and 1.44, 1.32-1.58, respectively). We have quantified a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients' records; we will update and extend results regularly.
    DOI:  https://doi.org/10.1038/s41586-020-2521-4
  4. Diabetes Metab Syndr. 2020 Jul 02. pii: S1871-4021(20)30234-4. [Epub ahead of print]14(5): 1017-1025
    Coronavirus disease (COVID-19): A systematic review and meta-analysis to evaluate the impact of various comorbidities on serious events.
    Kunal Nandy, Abhijeet Salunke, Subodh Kumar Pathak, Apurva Pandey, Chinmay Doctor, Ketul Puj, Mohit Sharma, Abhishek Jain, Vikas Warikoo.
       BACKGROUND AND AIMS: Currently there is limited knowledge on medical comorbidities and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of various morbidities on serious events in COVID 19.
    METHODS: PubMed, Cochrane Central Register of Clinical Trials were searched on April 28, 2020, to extract published articles that reported the outcomes of COVID-19 patients. The search terms were "coronavirus" and "clinical characteristics". ICU admission, mechanical ventilation, ARDS, Pneumonia, death was considered serious events. The comorbidities assessed in the study were Hypertension (HTN), Diabetes mellitus (DM), Cardiovascular diseases (CVD), Chronic obstructive pulmonary disease (COPD) and Chronic Kidney disease (CKD). Subsequently, comparisons between comorbidity patient group and the non-comorbidity patient groups, in terms of serious events were made using the pooled estimates of odd's ratio (OR) RESULTS: We identified 688 published results and 16 studies with 3994 patients were included in the systematic review. Serious events were seen in 526(13.16%) patients. Presence of hypertension with OR 2.95, diabetes mellitus with OR 3.07, Cardio vascular disease with OR 4.58, COPD with OR 6.66 and Chronic kidney disease with OR 5.32 had significant association in patients with COVID 19 on having serious events. Presence of diabetes mellitus (OR 2.78)) had a significant impact on death in COVID 19 patients with a p-value 0.004.
    CONCLUSIONS: Presence of medical comorbidities in COVID-19 leads to higher risk of developing serious events i.e. ICU admission, mechanical intubation and mortality. The presence of Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.
    Keywords:  COVID-19; Cancer; Comorbidities; Corona disease; Diabetes mellitus; Hypertension
    DOI:  https://doi.org/10.1016/j.dsx.2020.06.064
  5. Diabetol Metab Syndr. 2020 ;12 57
    Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease.
    Hadith Rastad, Hossein Karim, Hanieh-Sadat Ejtahed, Ramin Tajbakhsh, Mohammad Noorisepehr, Mehrdad Babaei, Mehdi Azimzadeh, Alireza Soleimani, Seyed Hasan Inanloo, Neda Shafiabadi Hassani, Fariba Rasanezhad, Ehsan Shahrestanaki, Zeinab Khodaparast, Hossein Golami, Mostafa Qorbani.
       Background: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD.
    Methods: This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: "DM" (having DM with or without other comorbidities), "only DM" (having DM without other comorbidities), "CVD" (having CVD with or without other comorbidities), "only CVD" (having CVD without other comorbidities), and "having any comorbidity". Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities.
    Results: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14-2.30)) and only DM (1.69 (1.05-2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, "having any comorbidities" increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95% CI 2.09-3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05).
    Conclusions: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.
    Keywords:  COVID-19; Cardiovascular diseases; Death; Diabetes
    DOI:  https://doi.org/10.1186/s13098-020-00565-9
  6. Arch Pathol Lab Med. 2020 Jul 10.
    A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity.
    Elena Aloisio, Mariia Chibireva, Ludovica Serafini, Sara Pasqualetti, Felicia S Falvella, Alberto Dolci, Mauro Panteghini.
      Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and ≤18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.
    Keywords:  COVID-19; albumin; biomarkers; cardiac troponin T; lactate dehydrogenase; prognosis; severe acute respiratory syndrome coronavirus 2
    DOI:  https://doi.org/10.5858/arpa.2020-0389-SA
  7. Diabetes Res Clin Pract. 2020 Jul 02. pii: S0168-8227(20)30547-7. [Epub ahead of print] 108295
    Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis.
    Rizwana Parveen, Nouroz Sehar, Ram Bajpai, Nidhi Bharal Agarwal.
       AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease.
    METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients.
    RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%).
    CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.
    Keywords:  COVID-19; SARS-CoV-2; coronavirus; diabetes; hypertension
    DOI:  https://doi.org/10.1016/j.diabres.2020.108295
  8. Int J Equity Health. 2020 07 06. 19(1): 114
    Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank.
    Aniruddh P Patel, Manish D Paranjpe, Nina P Kathiresan, Manuel A Rivas, Amit V Khera.
      Preliminary reports suggest that the Coronavirus Disease 2019 (COVID- 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID- 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5-5.3) and Asian participants (odds ratio 2.2; 95%CI 1.5-3.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID- 19 hospitalization rates according to the Townsend Deprivation Index - a composite measure of socioeconomic deprivation - and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5-3.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.
    Keywords:  COVID-19; Health disparity; Race; Socioeconomic deprivation
    DOI:  https://doi.org/10.1186/s12939-020-01227-y
  9. EClinicalMedicine. 2020 Jun;23 100404
    The impact of ethnicity on clinical outcomes in COVID-19: A systematic review.
    Daniel Pan, Shirley Sze, Jatinder S Minhas, Mansoor N Bangash, Nilesh Pareek, Pip Divall, Caroline Ml Williams, Marco R Oggioni, Iain B Squire, Laura B Nellums, Wasim Hanif, Kamlesh Khunti, Manish Pareek.
       Background: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes.
    Methods: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1st December 2019-15th May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654.
    Findings: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity - 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups.
    Interpretation: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance.
    Funding: NIHR.
    Keywords:  Covid-19; Ethnic; Ethnicity; Review; Sars-cov-2
    DOI:  https://doi.org/10.1016/j.eclinm.2020.100404
  10. Ther Adv Chronic Dis. 2020 ;11 2040622320935765
    Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis.
    Konstantinos Farsalinos, Anastasia Barbouni, Konstantinos Poulas, Riccardo Polosa, Pasquale Caponnetto, Raymond Niaura.
       Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients.
    Methods: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis.
    Results: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8-9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16-0.25, p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19-0.30, p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06-2.20, p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27-0.74, p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19-0.38, p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24-0.48, p < 0.001).
    Conclusion: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.
    Keywords:  COVID-19; SARS-CoV-2; adverse outcome; hospitalization; inflammation; nicotine; smoking
    DOI:  https://doi.org/10.1177/2040622320935765
  11. Tob Induc Dis. 2020 ;18 58
    Smoking, SARS-CoV-2 and COVID-19: A review of reviews considering implications for public health policy and practice.
    Emily J Grundy, Taiba Suddek, Filippos T Filippidis, Azeem Majeed, Sophie Coronini-Cronberg.
       INTRODUCTION: There has been significant speculation regarding the association between the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen, coronavirus disease (COVID-19) and smoking. We provide an overview of the available literature regarding the association between smoking, risk of SARS-CoV-2 infection, and risk of severe COVID-19 and poor clinical outcomes, with the aim of informing public health policy and practice, particularly in England.
    METHODS: Publications were identified utilising a systematic search approach on PUBMED and Google Scholar. Publications presenting a systematic review or meta-analysis considering the association between smoking and SARS-COV-2 infection or COVID-19 outcomes were included.
    RESULTS: Eight studies were identified. One considered the relationship between smoking and the probability of SARS-CoV-2 infection, three considered the association between COVID-19 hospitalisation and smoking history, and six reviewed the association between smoking history and development of severe COVID-19. One study specifically investigated the risk of mortality. The studies considering risk of severe disease indicate that there is a significant association between COVID-19 and current or ever smoking.
    CONCLUSIONS: This is a rapidly evolving topic. Current analysis remains limited due to the quality of primary data, although, early results indicate an association between smoking and COVID-19 severity. We highly recommend public health messaging to continue focusing on smoking cessation efforts.
    Keywords:  COVID-19; SARS-CoV-2; coronavirus; public health; smoking
    DOI:  https://doi.org/10.18332/tid/124788
  12. Lancet Glob Health. 2020 Jul 02. pii: S2214-109X(20)30285-0. [Epub ahead of print]
    Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study.
    Pedro Baqui, Ioana Bica, Valerio Marra, Ari Ercole, Mihaela van der Schaar.
       BACKGROUND: Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Understanding the possible socioeconomic and ethnic health inequities is particularly important given the diverse population and fragile political and economic situation. We aimed to characterise the COVID-19 pandemic in Brazil and assess variations in mortality according to region, ethnicity, comorbidities, and symptoms.
    METHODS: We conducted a cross-sectional observational study of COVID-19 hospital mortality using data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) dataset to characterise the COVID-19 pandemic in Brazil. In the study, we included hospitalised patients who had a positive RT-PCR test for severe acute respiratory syndrome coronavirus 2 and who had ethnicity information in the dataset. Ethnicity of participants was classified according to the five categories used by the Brazilian Institute of Geography and Statistics: Branco (White), Preto (Black), Amarelo (East Asian), Indígeno (Indigenous), or Pardo (mixed ethnicity). We assessed regional variations in patients with COVID-19 admitted to hospital by state and by two socioeconomically grouped regions (north and central-south). We used mixed-effects Cox regression survival analysis to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation.
    FINDINGS: Of 99 557 patients in the SIVEP-Gripe dataset, we included 11 321 patients in our study. 9278 (82·0%) of these patients were from the central-south region, and 2043 (18·0%) were from the north region. Compared with White Brazilians, Pardo and Black Brazilians with COVID-19 who were admitted to hospital had significantly higher risk of mortality (hazard ratio [HR] 1·45, 95% CI 1·33-1·58 for Pardo Brazilians; 1·32, 1·15-1·52 for Black Brazilians). Pardo ethnicity was the second most important risk factor (after age) for death. Comorbidities were more common in Brazilians admitted to hospital in the north region than in the central-south, with similar proportions between the various ethnic groups. States in the north had higher HRs compared with those of the central-south, except for Rio de Janeiro, which had a much higher HR than that of the other central-south states.
    INTERPRETATION: We found evidence of two distinct but associated effects: increased mortality in the north region (regional effect) and in the Pardo and Black populations (ethnicity effect). We speculate that the regional effect is driven by increasing comorbidity burden in regions with lower levels of socioeconomic development. The ethnicity effect might be related to differences in susceptibility to COVID-19 and access to health care (including intensive care) across ethnicities. Our analysis supports an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect Pardo and Black Brazilians, as well as the population of poorer states, from their higher risk of dying of COVID-19.
    FUNDING: None.
    DOI:  https://doi.org/10.1016/S2214-109X(20)30285-0
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