PLOS ONE RESEARCH ARTICLE Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study Ezequiel Cordova ID1*, Analia Mykietiuk2, Omar Sued3, Lautaro De Vedia4, Natalia Pacifico4, Matias H. Garcia Hernandez5, Natalia M. Baeza5, Franco Garibaldi1, a1111111111 Maria Fernanda Alzogaray2, Rosa Contreras6, Lucrecia Soler Puy7, Pablo G. Scapellato8, a1111111111 Laura Barcelona9, Mariana L. Golikow10, Maria Florencia Piñeiro11, Hugo J. Miño12, Maria a1111111111 Fernanda Consalvo13, Corina Nemirovsky14, Marisa Sanchez14, Myrna Cabral15, a1111111111 Lucia Lamponi Tappata16, Mariano Blasco ID17, Jamile Ballivian18, Gustavo Lopardo9, a1111111111 Martin E. Stryjewski5*, on behalf of the ECCOVID study group¶ 1 Hospital Cosme Argerich, Ciudad Autónoma de Buenos Aires (CABA), Buenos Aires, Argentina, 2 Instituto Medico Platense—La Plata, Buenos Aires, Argentina, 3 Fundación Huésped—CABA, Buenos Aires, Argentina, 4 Hospital F.J. Muñiz—CABA, Buenos Aires, Argentina, 5 Centro de Educación Médica e Investigaciones Clı́nicas (CEMIC)—CABA, Buenos Aires, Argentina, 6 Hospital Dr. Marcial V. Quiroga—San OPEN ACCESS Juan, San Juan, Buenos Aires, Argentina, 7 Hospital Julio C. Perrando—Resistencia, Chaco, Buenos Aires, Argentina, 8 Hospital Santojanni—CABA, Buenos Aires, Argentina, 9 Hospital Prof. Dr. Bernardo A. Citation: Cordova E, Mykietiuk A, Sued O, De Vedia Houssay—Vicente Lopez, Buenos Aires, Argentina, 10 Hospital Nacional Posadas—El Palomar, Buenos L, Pacifico N, Garcia Hernandez MH, et al. (2021) Aires, Argentina, 11 Hospital Fernandez—CABA, Buenos Aires, Argentina, 12 Hospital Iturraspe—Santa Fe, Clinical characteristics and outcomes of Santa Fe, Argentina, 13 Hospital Penna–CABA, Buenos Aires, Argentina, 14 Hospital Italiano—CABA, hospitalized patients with SARS-CoV-2 infection in Buenos Aires, Argentina, 15 Hospital Central—Mendoza, Mendoza, Argentina, 16 Hospital Leonidas Lucero a Latin American country: Results from the —Bahı́a Blanca, Buenos Aires, Argentina, 17 Sanatorio Agote—CABA, Buenos Aires, Argentina, 18 Helios ECCOVID multicenter prospective study. PLoS ONE Salud–CABA, Buenos Aires, Argentina 16(10): e0258260. https://doi.org/10.1371/journal. ¶ Membership of the ECCOVID study group is provided in the Acknowledgments. pone.0258260 * dr_ecordova@hotmail.com (EC); stryj002@gmail.com (MES) Editor: José Moreira, Fundacao Oswaldo Cruz, BRAZIL Received: April 6, 2021 Abstract Accepted: September 22, 2021 Background Published: October 8, 2021 Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The Copyright: © 2021 Cordova et al. This is an open aim of this study was to describe clinical characteristics and outcomes in a cohort of patients access article distributed under the terms of the hospitalized with SARS-CoV-2 in Argentina. Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original Methods author and source are credited. Multicenter prospective cohort study of �18 years-old patients with confirmed SARS-CoV-2 Data Availability Statement: All relevant data are infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regres- within the manuscript and its Supporting sion models were used to identify variables associated with 30-day mortality and admission Information files. to intensive care unit (ICU). Funding: This work was supported by the Argentinean Society of Infectious Diseases (SADI) Results https://www.sadi.org.ar/ The study was designed by the Sub-committee of Research at the A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% Argentinean Society of Infectious Diseases (SADI). had at least one comorbidity. The most common comorbidities were hypertension (32%), PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 1 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Competing interests: Ezequiel Cordova is a obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild consultant for Sinocell tech, Oncotelic and 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required Janssen, is a speaker for Janssen, and received research grants from ViiV. Martin E. Stryjewski is a supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was consultant for Basilea and Fulcrum, is a speaker for 11%. Factors independently associated with ICU admission were male gender (OR 1.81; Pfizer, received research grants from NIH ARLG 95%CI 1.16–2.81), hypertension (OR 3.21; 95%CI 2.08–4.95), obesity (OR 2.38; 95%CI (UM1A104681), and is a sub-investigator in 1.51–3.7), oxygen saturation �93% (OR 6.45; 95%CI 4.20–9.92) and lymphopenia (OR INSIGHT 0013 trial (NIH). Omar Sued is a consultant for ViiV, Eurofarma and Abbvie, and 3.21; 95%CI 2.08–4.95). Factors independently associated with 30-day mortality included received research grants from NIH, Richmond age �60 years-old (OR 2.68; 95% CI 1.63–4.43), oxygen saturation �93% (OR 3.19; 95% Laboratory and ViiV. None of these conflicts are CI 1.97–5.16) and lymphopenia (OR 2.65; 95%CI 1.64–4.27). relevant to this article. All other authors report no conflicts of interest relevant to this article. This does not alter our adherence to PLOS ONE policies Conclusions on sharing data and materials. This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina. Introduction The novel epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pro- ducing COVID-19 disease has rapidly escalated to pandemic proportions [1]. To date over one hundred million humans have been infected and around two million have died due to COVID-19 [2]. Several reports all over the world have described clinical features and outcomes of such patients [3–6]. However, these studies may differ widely in different countries and regions [1, 7]. In addition, many clinical observations from specific cities, states or countries may not apply to other territories or populations. Therefore, it is crucial to have prospective clinical information on the outcomes and predictors on COVID-19 in each country or region. On March 3rd, 2020, the first case in Argentina was confirmed. Since then, more than two million subjects have been infected and over 50 thousand have died with COVID-19 in the country [2]. Epidemiological studies conducted in Argentina are already available [8, 9]. How- ever, these studies lack detailed clinical information. Therefore, such clinical data is still needed in the country. The aim of this study was to describe the clinical characteristics, outcomes and predictors of ICU admission and death in a multicenter prospective cohort of patients hospitalized with COVID-19 in Argentina. Methods Study design The ECCOVID study is an ongoing multicenter prospective observational cohort study con- ducted in 19 hospitals in Argentina. The aim of the study is to assess clinical and epidemiologi- cal characteristics of patients admitted with COVID-19 in the country. The study was designed by the Sub-committee of Research at the Argentinean Society of Infectious Diseases (SADI) Participants Patients were enrolled in the study if they had �18 years old, were admitted in a participating center, had SARS-CoV-2 infection confirmed by polymerases chain reaction (PCR) or other PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 2 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina validated methods on nasopharyngeal swab or other respiratory specimens, and had consented participation in the study. Patients were consecutively enrolled between March 3rd, 2020, and October 15th, 2020. Data collection Routine care data was prospectively extracted from the medical records and entered into a Redcap database (Research Electronic Data Capture, Vanderbilt University, US) hosted by SADI. Main clinical, epidemiological, radiological and laboratory variables were captured within 24 hours from admission, respectively. Patients were followed during hospitalization and at 30, 60 and 180 days. For those patients who were alive and not hospitalized a telephonic follow up was accepted. All relevant treatments and interventions were obtained during hospi- talization. Disease severity was classified as mild, moderate, severe, or critical [10]. Outcomes The main outcome for this analysis was mortality at 30-days from the index admission. The secondary outcome was admission at the intensive care unit (ICU). Missing data As the main and secondary outcomes of the study were mainly descriptive, no imputation of missing data was performed. To reduce the impact of missing data on outcome analyses, we restricted such analyses to patients who had been admitted for at least a month before data extraction. Statistical analyses Categorical variables were described using absolute and relative frequencies. Continuous vari- ables were described using medians and interquartile ranges (IQR). Comparisons between groups were made using Mann Whitney U test or Kruskal-Wallis test for continuous variables, or X2 test for categorical variables, as appropriate. All tests were two-sided and considered sig- nificant if p-value was less than 0.05. To investigate the effect of different factors on 30-day mortality, we performed a cross sec- tional analysis using a multivariable logistic regression model. Backwards stepwise model selection with a p-value of 0.05 was conducted. However, variables known from previous stud- ies to be associated with 30-day mortality were forced into the model. To assess the fit of the model, we performed Hosmer-Lemeshow goodness of fit test. Data analyses were performed using R (R Core Team version 4.0.3, Vienna, Austria). Ethics Informed consent was obtained according to each participating Ethic Committees. Results From March 3rd to October 15th, 2020, 1074 patients with �18 years old who had at least 30-day follow up were prospectively enrolled in the ECCOVID study. Critical variables were fully available in 809 of these subjects who were included in the present analysis. The median age was 53 years (IQR 38–67); 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Baseline characteristics in the overall population and by gender are shown in Table 1. PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 3 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Table 1. Baseline characteristics among 809 hospitalized patients with COVID-19 in Argentina. Characteristics Male Female All n = 456 n = 353 n = 809 Age at admission median (interquartile range) in years 54 (38–70) 52 (38–65) 53 (38–67) < 60 years 306 (67.1%) 215 (60.9%) 521 (64.4%) > 60 years 150 (32.9%) 138 (39.1%) 288 (35.6%) Any comorbidity No 140 (30.7%) 93 (26.3%) 233 (28.8%) Yes 316 (69.3%) 260 (73.7%) 576 (71.2%) Diabetes No 384 (84.2% 287 (81.3%) 671 (82.9%) Yes 72 (15.8%) 66 (18.7%) 138 (17.1%) Chronic pulmonary disease, not asthma No 438 (96.1%) 344 (97.5%) 782 (96.7%) Yes 18 (3.9%) 9 (2.5%) 27(3.3%) Asthma No 435 (95.4%) 321 (90.9%) 756 (93.4%) Yes 21 (4.6%) 32 (9.1%) 53 (6.6%) Hypertension No 323 (70.8%) 228 (64.6%) 551 (68.1%) Yes 133 (29.2%) 125 (35.4%) 258 (31.9%) Obesity No 355 (77.9%) 266 (75.4%) 621 (76.8%) Yes 101 (22.1%) 87 (24.6%) 188 (23.2%) Chronic kidney disease No 433 (95%) 343 (97.2%) 776 (95.9%) Yes 23 (5%) 10 (2.8%) 33 (4.1%) AIDS/HIV No 439 (96.3%) 347 (98.3%) 786 (97.2%) Yes 17 (3.7%) 6 (1.7%) 23 (2.8%) Solid malignancy No 438 (96.1%) 335 (94.9%) 773 (95.6%) Yes 18 (3.9%) 18 (5.1%) 36 (4.4%) Cardiac disease No 418 (91.7%) 332 (94.1%) 750 (92.7%) Yes 38 (8.3%) 21 (5.9%) 59 (7.29%) Immunosuppression No 442(96.9%) 345 (97.7%) 787 (89.2%) Yes 14 (3.1%) 8 (2.3%) 87 (10.8%) Death at 30-day follow up No 399 (87.5%) 321 (90.93%) 720 (89%) Yes 57 (12.5%) 32 (9.07%) 89 (11%) https://doi.org/10.1371/journal.pone.0258260.t001 Most frequent symptoms reported prior to or at admission were fever (61%), cough (60%) and dyspnea (40%) (Table 2). At admission almost one third of the patients (30%) had abnor- mal body temperature (�37.5˚C) and 18.5% had fever (�38˚C). Disease severity at admission was mild in 25%, moderate in 51%, severe in 17%, and critical in 7% of patients. Oxygen satu- ration �93% was observed in about 20% cases. The median time from symptoms onset to hos- pitalization was 5 days (IQR 2–7). Approximately one fifth of the patients (21%) did not present symptoms of upper or lower respiratory tract infection. PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 4 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Table 2. Disease severity, signs, symptoms, and radiology findings among 809 hospitalized patients with COVID- 19 in Argentina. VARIABLE N (%) Disease severity Mild 204 (25%) Moderate 409 (51%) Severe 139 (17%) Critical 57 (7%) Signs Temp 37.5–37.9˚C (n = 779) 91 (11.6%) Temp �38˚C (n = 779) 144 (18.5%) Respiratory rate �20 x min 416 (51.4%) Heart rate �100 x min 218 (26.9%) Oxygen saturation � 93% 172 (21.3%) Symptoms Cough 489 (60.4%) Shortness of breath 327 (40.4%) Myalgia 238 (29.4%) Sore throat 234 (28.9%) Headache 149 (18.4%) Anosmia 148 (18.3%) Ageusia 129 (15.9%) Diarrhea 108 (13.3%) Chilling 97 (12.0%) Expectoration 64 (7.9%) Chest pain 59 (7.3%) Rhinorrhea 55 (6.8%) Abdominal pain 46 (5.7%) Conjunctival congestion 9 (1.1%) Other 55 (6.8%) Radiology findings Chest radiography (n = 618) Abnormal findings 365 (59.5%) Bilateral interstitial infiltrate 277 (75.9%) Unilateral interstitial infiltrate 56 (15.3%) Unilateral consolidation pattern 56 (15.3%) Bilateral consolidation pattern 35 (9.6%) Pleural effusion 10 (2.7%) Chest computer tomography (n = 397) Abnormal findings 340 (85.6%) Bilateral ground glass opacities 291 (85.6%) bilateral consolidation 60 (17.6%) Unilateral ground glass opacities 34 (10%) Unilateral consolidation 29 (8.5%) Pleural effusion 19 (5.6%) https://doi.org/10.1371/journal.pone.0258260.t002 Chest Radiographs were performed at admission in 618 patients (76%). Abnormal findings were present in almost 60% of these patients. The most common radiographic patterns were bilateral interstitial infiltrates (75.9%). Chest computed tomography (CT) was obtained in 397 PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 5 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Table 3. Laboratory findings at hospital admission among patients with COVID-19 in Argentina. Variable N Median (IQR) or % Hemoglobin (g/dL) 799 13.6 (12.2–14.7) White blood cell count (x109 /L) 809 6.4 (4.87–8.5) Lymphocytes (x109 /L) 809 1.3(0.9–1.8) 9 � 1 x x10 /L 252 31.1% Platelets (x109 /L) 750 220 (176–277) � 150 x 109 /L 750 10.9% Creatinine (mg/dL) 791 0.80 (0.66–0.98) � 1.5 50 6.3% AST (U/L) 773 32.5 (23–53) ALT (U/L) 773 32 (19–56) Increased AST and/or ALT � x2 UNL 123 15.9% Lactate dehydrogenase (LDH) (U/L) 653 442 (327–617) �500 272 41.7% C-reactive protein (mg/L) 420 10 (2.7–35) �1 360 85.5% D-dimer (μg/ml) 420 0.53 (0.30–1) �1 107 25.5% Ferritin (ng/mL) 391 415 (158–922) >500 172 44% ALT: alanine transaminase; AST: aspartate transaminase; UNL: upper normal limit. https://doi.org/10.1371/journal.pone.0258260.t003 patients (49%). Abnormal findings were present in 86% of such patients. Bilateral ground glass opacities were the most frequent finding on CT. Over 20% of the patients with normal chest radiograph had lung infiltrates on the chest CT. In patients who were admitted without respi- ratory symptoms, radiographic infiltrates on chest radiographs or CT were observed in 38.6% and 72.2% of cases, respectively. Laboratory findings at baseline are presented in Table 3. Lym- phopenia was observed in 31% of the patients. Elevated alanine transaminase (ALT) or aspar- tate transaminase (AST) (2 times above the upper normal limit) was found in 15.9% of the patients. D-dimer levels were available in 420 patients and found to be �1.0 μg/mL in 25% of these patients. Patients with severe or critical COVID-19 had lower lymphocyte count (1100 vs 1400 cells/mL; p<0.001), higher C-reactive protein (CRP) (27.5 mg/L vs. 6 p<0.001), D-dimer (0.9 vs. 0.5 μg/ml; p<0.001) and ferritin levels (780 vs. 344 ng/mL; p<0.001), respectively. During hospitalization almost half (49%) required oxygen supplementation, 18% ICU, and 12% invasive mechanical ventilation, respectively. Of those admitted to ICU, 70% required mechanical ventilation. The median time to ICU admission was 7 days (IQR 4–9) from onset of symptoms and 1 day (IQR 0–4) from hospitalization. The median duration of mechanical ventilation was 12 days (IQR 6–18). Overall, 30-day mortality was 11%. The median time between hospital admission and death was 15 days (IQR 9–21). In patients requiring oxygen supplementation mortality at 30 days was 10.8% for patients in the general ward, 36.6% in those admitted to ICU, and 50.5% in patients undergoing invasive mechanical ventilation. Clinical outcomes are displayed in Table 4 whereas Fig 1 shows 30-day mortality by age group. In the multivariable analysis factors independently associated with ICU admission were male gender (OR 1.81; 95% CI 1.16–2.81), arterial hypertension (OR 3.21; 95% CI 2.08–4.95), obesity (OR 2.38; 95%CI 1.51–3.7), oxygen saturation �93% (OR 6.45; 95% CI 4.20–9.92) and lymphopenia (lymphocyte count <1000 cell/mL) (OR 3.21; 95%CI 2.08–4.95) (Hosmer- PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 6 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Table 4. Clinical outcomes and dispositions among 809 patients hospitalized with COVID-19 in Argentina. Variable N Median (IQR) or (%) Admission at general ward 752 93% Admission at ICU 57 7% Step up ICU admission a 85 11.3% Oxygen requirement 392 48.5% Mechanical ventilation 97 12% Duration of mechanical ventilation (days) 97 12 (6–18) Shock 88 10.9% Renal replacement therapy 17 2.1% Length of stay in general ward (days) b 667 10 (6–15) Length of stay in ICU (days)c 142 10 (5–19) Do-not-resuscitate status 39 4.8% Discharged at 30 days 665 82.2% Death at 30-days 89 11% Among patients in ICU 52 36.6% ICU: intensive care unit. a. Among patients initially admitted to a general ward (n = 752). b. From admission to discharge or death. c. From ICU admission to discharge to a general ward or death. https://doi.org/10.1371/journal.pone.0258260.t004 Lemeshow X2 = 8.4, df = 7, p-value = 0.30) (Table 5). Factors at admission independently asso- ciated with 30-day mortality in the multivariable model included age �60 years-old (OR 2.68; 95% CI 1.63–4.43), oxygen saturation �93% at admission (OR 3.19; 95%CI 1.97–5.16) and lymphopenia (OR 2.65; 95% CI 1.64–4.27) (Hosmer-Lemeshow X2 = 3.36, df = 8, p- value = 0.91) (Table 6). Discussion In this prospective multicenter study, we analyzed over 800 patients hospitalized with COVID-19 in Argentina. To our knowledge this is the first large and detailed clinical report in Fig 1. 30-day mortality by age group among 809 patients hospitalized with COVID-19 in Argentina. https://doi.org/10.1371/journal.pone.0258260.g001 PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 7 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Table 5. Multivariable analysis of characteristics associated with intensive care unit admission among 809 patients with COVID -19 in Argentina. Variables Unadjusted OR Adjusted OR (95% CI) (95% CI) Gender male 1.75 (1.19–2.58) 1.81 (1.16–2.81) Age � 60 years 1.49 (1.03–2.17) 0.90 (0.54–1.53) Oxygen saturation �93% at admission 7.65 (5.13–11.42) 6.45 (4.20–9.92) Lymphocyte count <1000 cell/ml at admission 3.32 (2.28–4.84) 3.21 (2.08–4.95) Arterial hypertension 2.21 (1.66–4.53) 1.93 (1.14–3.26) Obesity 2.68 (1.81–3.96) 2.38 (1.51–3.7) COPD 0.60 (0.18–2.02) 0.32 (0.08–1.21) Diabetes 1.97 (1.28–3.04) 0.91 (0.53–1.59) Cardiac disease 1.57 (0.84–2.95) 0.96 (0.45–2.1) Solid malignancy 0.43 (0.13–1.42) 0.44 (0.12–1.61) https://doi.org/10.1371/journal.pone.0258260.t005 our country which provides several important findings allowing better understanding on the pandemic in the country. First, the current study comprehensively describes clinical and demographic characteristics of patients admitted with SARS-Cov-2 infection in Argentina. Overall, we found in our study population similar comorbidities to those prevalent in different COVID-19 reports such as hypertension, obesity, and diabetes [4–6]. The median age in our cohort of patients (52 years old) was comparable to those reported in large epidemiological studies including hospitalized patients with COVID-19 in Argentina [8] and elsewhere [5, 6]. The most frequent symptoms among hospitalized patients with COVID-19 were fever, cough, and shortness of breath. Anos- mia and ageusia were found in less than 20% of cases which were also in agreement with other published cohorts [5, 6, 8, 9, 11, 12]. Interestingly only 20% of our patients had fever (� 38C) and a similar percentage lacked any respiratory symptoms at admission. Taken together this information indicates that neither fever nor respiratory symptoms are reliable markers of infection due to SARS-CoV-2 among patients requiring hospitalization. Second, both radiologic and laboratory findings were also important. Most patients in our study had evidence of lung infiltrates on chest images at admission. As previously reported, chest CT had a better diagnostic accuracy than chest radiographic [13]. Characteristics of the lung infiltrates were similar to other descriptions [5, 14, 15]. In addition, we were also able to identify infiltrates in a significant proportion of those individuals without respiratory symp- toms (72.2%). A CT scan is a valuable diagnostic tool that help to diagnose COVID-19 in patients with either difficult or negative images on the chest X rays [14, 16] as well as in those patients with absence of respiratory symptoms. In the laboratory analysis we have also found markers of systemic inflammation such as CRP in a vast majority of our patients (in whom the Table 6. Multivariable analysis of characteristics associated with death at 30-days among 809 patients hospitalized with COVID-19 in Argentina. Variables Unadjusted OR Adjusted OR (95% CI) (95% CI) Gender male 1.43 (.91–2.26) 1.43 (.87–2.33) Age � 60 years 3.77 (2.38–5.97) 2.68 (1.63–4.43) Oxygen saturation �93% at admission 4.28 (2.71–6.76) 3.19 (1.97–5.16) Lymphocyte count <1000 cell/ml at admission 3.65 (2.33–5.74) 2.65 (1.64–4.27) Any comorbidity 3.16 (1.65–6.06) 1.76 (0.87–3.55) https://doi.org/10.1371/journal.pone.0258260.t006 PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 8 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina test was performed). The current knowledge indicates that patients with severe COVID-19 or those with adverse outcomes have increased levels of inflammatory cytokines as well as other infection-related biomarkers [12, 17–20]. However, these laboratory parameters, mainly D- dimer, CRP and ferritin are not easily available in health-care centers with limited resources. In the present cohort, only around half of our patients had CRP or D-dimer determined at admission. Therefore, simple laboratory parameters should be used to identify patients at risk of adverse outcomes in our population. Third, the outcomes of our patients are also worthy to mention. In our study the median time from symptoms onset to hospitalization or ICU admission was 5 and 7 days, respectively. These findings are consistent with other reports [18, 21, 22]. Similarly, the overall 30-day mor- tality in our cohort of patients was 11%. Solidarity trial with a total of 11,330 patients from 405 hospitals in 30 countries reported a 28-day in-hospital death of 11.8% [23]. Near half of patients in our study requiring mechanical invasive ventilation died. This mortality rate also reflects the one reported in a recent meta-analysis with over 55.000 patients in 69 studies across 23 countries [24]. Finally, risk factors for ICU admission were male sex, arterial hypertension, obesity, oxygen saturation �93% and lymphopenia at admission. These risk factors identified are in agreement with other investigations [22, 25]. Age over 60 years was not found as an independent risk fac- tor for ICU admission in our study. However, we found that this variable was associated with 30-day mortality. A possible explanation for these contradictory results is that older patients (�80 year) were not necessarily transferred to ICUs based on several medical, familiar, or legal considerations [26]. On the other hand, independent risk factors for 30-day mortality sorted out by our study were age over 60 years old, oxygen saturation �93% and lymphopenia. In contrast to other reports [6, 9, 27], we did not detect an independent effect of gender or comorbidities on 30-day mortality. Probably, these variables were attenuated by the strong effect of age, markers of severe lung involvement such as hypoxemia and/or immune alter- ations such as lymphopenia. Our study had some limitations. First, the adverse clinical outcomes may be underestimated by the fact that hospitalization was mandatory until June 2020 for all patients with SARS-CoV- 2 in Argentina, including those with mild or moderate disease. However, most of the enroll- ment in this study occurred when hospitalization was not mandatory for such cases. Second, the complete cohort enrolled was not analyzed in this report. Enrollment which has occurred at the end of the study period was under ongoing collection of data at the time of this analysis. Given the similarity of results in the current study with several others, it is probable that this partial analysis truly reflects the real universe of patients hospitalized with COVID-19 in Argentina. Last, variables associated with ICU admission or 30-day mortality were not vali- dated in a complementary dataset of subjects. Despite these limitations we believe our study provides key clinical information to better understand the characteristics of patients hospital- ized with COVID-19. The current investigation further validates in our population several observations made in patients hospitalized with COVID-19 in different world regions. Finally, using clinical and laboratory parameters available at bedside this study identifies factors associ- ated with adverse clinical outcomes in patients hospitalized with COVID-19. Supporting information S1 Data. (XLSX) PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 9 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Acknowledgments ECCOVID Study Group (Argentina): • Martin E. Stryjewski, Matias H. Garcia Hernandez, Natalia M. Baeza. Centro de Educación Médica e Investigaciones Clı́nicas (CEMIC)—Ciudad Autonoma de Buenos Aires (CABA), Argentina • Ezequiel Cordova, Franco Garibaldi, Claudia Rodriguez. Hospital Cosme Argerich–CABA, Argentina • Lautaro de Vedia, Natalia Pacı́fico, Ana Garcı́a, Marisa Fernández. Hospital FJ Muñiz— CABA, Argentina • Myrna Cabral. Hospital Central—Mendoza, Mendoza, Argentina • Rosa Contreras. Hospital Dr. Marcial V. Quiroga—San Juan, San Juan, Argentina • Maria Florencia Piñeiro, Sonia López Griskan. Hospital Fernandez–CABA, Argentina • Corina Nemirovsky, Marisa Sánchez. Hospital Italiano–CABA, Argentina • Hugo Juan Damián Miño, Delfina Godano, Federico Barbone. Hospital Iturraspe—Santa Fe, Santa Fe, Argentina • Lucı́a Lamponi Tappatá, Diego Maurizi. Hospital Leonidas Lucero—Bahia Blanca, Buenos Aires, Argentina • Mariana Lorena Golikow, Florencia Marina Riveros. Hospital Nacional Posadas—El Palo- mar, Buenos Aires, Argentina • Maria Fernanda Consalvo. Hospital Penna–CABA, Argentina • Laura Barcelona, Gustavo Lopardo. Hospital Prof. Dr Bernardo A. Houssay—Vicente Lopez, Buenos Aires, Argentina • Pablo Scapellato, Sofı́a Sábato, Ivana Coloiani, Iael Altclas. Hospital Santojanni–CABA, Argentina • Analia Mykietiuk, Marı́a Fernanda Alzogaray, Bettina Cooke, Lucı́a Galeano, Natalia Spi- nelli. Instituto Medico Platense—La Plata, Buenos Aires, Argentina • Gabriela Vidiella, Mariano Blasco, Agustina Tortoriello. Sanatorio Agote–CABA, Argentina • Florencia Otermin. Hospital Italiano de la Plata, La Plata, Buenos Aires, Argentina • Esteban Nannini, Mariángeles Fenes. Sanatorio Británico–Rosario, Santa Fe, Argentina • Lucrecia Soler Puy, Silvana Fernandez Lugo. Hospital Julio C. Perrando—Resistencia, Chaco, Argentina • Jamile Ballivian. Helios Salud–CABA, Argentina • Omar Sued. Fundación Huésped–CABA, Argentina • Javier Farina. Hospital de Alta Complejidad Cuenca Alta SAMIC–Cañuelas, Buenos Aires, Argentina PLOS ONE | https://doi.org/10.1371/journal.pone.0258260 October 8, 2021 10 / 12 PLOS ONE SARS-CoV-2 hospitalized patients in Argentina Author Contributions Conceptualization: Ezequiel Cordova, Analia Mykietiuk, Omar Sued, Corina Nemirovsky, Gustavo Lopardo, Martin E. Stryjewski. Data curation: Ezequiel Cordova, Analia Mykietiuk, Martin E. Stryjewski. Formal analysis: Ezequiel Cordova, Jamile Ballivian. Investigation: Ezequiel Cordova, Analia Mykietiuk, Lautaro De Vedia, Natalia Pacifico, Matias H. Garcia Hernandez, Natalia M. Baeza, Franco Garibaldi, Maria Fernanda Alzo- garay, Rosa Contreras, Lucrecia Soler Puy, Pablo G. Scapellato, Laura Barcelona, Mariana L. Golikow, Maria Florencia Piñeiro, Hugo J. Miño, Maria Fernanda Consalvo, Corina Nemirovsky, Marisa Sanchez, Myrna Cabral, Lucia Lamponi Tappata, Mariano Blasco, Martin E. Stryjewski. 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