Prognosis of Critically Ill Patients With Acute Respiratory Failure Due To The SARS-CoV-2 501Y.V2 Variant: A Multicenter Retrospective Matched Cohort Study

Prognosis of Critically Ill Patients With Acute Respiratory Failure Due To The SARS-CoV-2 501Y.V2 Variant: A Multicenter Retrospective Matched Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognosis of Critically Ill Patients With Acute Respiratory Failure Due To The SARS-CoV-2 501Y.V2 Variant: A Multicenter Retrospective Matched Cohort Study Bérénice Puech, Antoine Legrand, Olivier Simon, Chloé Combe, Marie-Christine Jaffar-Bandjee, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-806080/v2 This work is licensed under a CC BY 4.0 License Status: Under Review Version 2 posted 8 You are reading this latest preprint version Show more versions Abstract Background The aim of this study was to compare the prognosis of patients with acute respiratory failure (ARF) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant 501Y.V2 to that of patients with ARF due to the original strain. Methods This retrospective matched cohort study included all consecutive patients who were hospitalized for ARF due to SARS-CoV-2 in Reunion Island University Hospital between March 2020 and March 2021. Twenty-eight in hospital mortality was evaluated before and after matching. Results A total of 218 patients with ARF due to SARS-CoV-2 were enrolled in the study. Of these, 83 (38.1%) were infected with the 501Y.V2 variant. During intensive care unit stay, 104 (47.7%) patients received invasive mechanical ventilation and 20 (9.2%) patients were supported by venovenous extracorporeal membrane oxygenation. Patients infected with the 501Y.V2 variant were younger (58 [51–68] vs. 67 [56–74] years old, P = 0.003), had less hypertension (54.2% vs 68.1%, P = 0.04), and had less chronic kidney disease (13.3% vs. 31.9%, P = 0.002) than patients infected with the original strain. After controlling for confounding variables (62 matched patients in each group), 28-day mortality was higher in the group of patients infected with the 501Y.V2 variant (30.6%) than in the group of patients infected with the original strain (19.4%, P = 0.04). Conclusion In Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients with ARF infected with the 501Y.V2 variant than in patients infected with the original strain. Health Policy General Microbiology Virology SARS-CoV-2 COVID-19 501Y.V2 Acute respiratory failure acute respiratory distress syndrome Figures Figure 1 Figure 2 Introduction An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in China in December 2019 began to spread globally in January 2020. 1 Reunion Island (845,000 inhabitants), a French overseas department located in the Indian Ocean, was relatively spared by the SARS-CoV-2 pandemic until February 2021. 2 From the first detected case of SARS-CoV-2 infection on 19 March 2020 until 4 February 2021, only 10,330 cases and 5,4 deaths per 100,000 inhabitants were reported on the island. 2 These figures are likely due to the protective effects of climatic and environmental factors against SARS-CoV-2 transmission 3–5 and to the geographical characteristics of Reunion Island (i.e. an insular territory with the international airport as its only entry point). To this is added the fact the local health care system meets European standards (16 extracorporeal membrane oxygenation supports, coronary angiography, all type of surgeries, etc.), and was therefore able to handle all cases without reaching saturation. In recent months, several SARS-CoV-2 variants of concern have been spreading worldwide. These are a source of worry as they may lead to: reinfection of SARS-CoV-2 recovered individuals; 6 lower effectiveness of vaccines; 7,8 a higher transmission rate; 9 and more severe pathogenicity. 9,10 The 501Y.V2 variant, which has three mutations to the spike protein, first appeared in the Eastern Cape Province of South Africa in October 2020 and then spread to other countries. 11,12 In Reunion Island, the first case of the 501Y.V2 variant was isolated on 4 January 2021 in a patient transferred from the Comoros for acute respiratory failure (ARF). Since then, the incidence of SARS-CoV-2 infection has increased 3-fold on the island. 2 In Mayotte, another French overseas department in the Indian Ocean, the incidence has increased 17-fold since the 501Y.V2 variant was first detected in January. 2,13 The 501Y.V2 variant is now the most common variant in Reunion Island, Mayotte, and the neighboring islands of the Comoros archipelago. 2,13 At present, no clinical data are available on the pathogenicity of ARF due to SARS-CoV-2 variant 501Y.V2. The aim of this study was to compare the prognosis of patients with ARF due to the 501Y.V2 variant to that of patients with ARF due to the original strain. Methods All methods were performed in accordance with the French legislation on non-interventional studies. This study was registered with the National Institute of Health Data under the number MR4-04 (2206739) and approved by the Ethics Committee of the French Society of Infectious Disease and Tropical Medicine (CER-MIT 2021-N°00011642). Written and oral Informed Consent was obtained from all participants after they were given a written information notice about the process of data collection. All methods were performed in accordance with the relevant guidelines and regulations. This study complies with the Strengthening the Reporting of Observational studies in Epidemiology recommendations statement. 14 Selection of the study sample All consecutive patients with ARF due to SARS-CoV-2 who were hospitalized in one of the three intensive care units (ICUs) of Reunion Island University Hospital between 1 March 2020 and 18 April 2021 were included in the study ((Félix Guyon University Hospital, Saint-Pierre University hospital and Saint-Paul Hospital). Acute respiratory failure was defined as bilateral pulmonary infiltrates on chest X-ray or computed tomography scan and need for high-flow nasal cannula oxygenation or invasive mechanical ventilation. All patients with a nasopharyngeal or respiratory sample that tested positive for SARS-CoV-2 by real-time reverse transcription-polymerase chain reaction (RT-PCR) targeting the IP2 and IP4 regions and the N gene were evaluated. All positive samples were analyzed using NucliSens easyMAG system (BioMérieux). From 1 January 2021 onwards, positive samples were also analyzed by genome sequencing using Oxford Nanopore technology, as per the Artic Network’s overlapping amplicon protocol. 15,16 Therapeutic management In accordance with our protocol, all patients with ARF due to SARS-CoV-2 were treated with: (1) dexamethasone at a dosage of 6 mg/day for 10 days; 17 (2) deworming with ivermectine or albendazole; and (3) enhanced anticoagulation, as per the guidelines of the French Society of Thrombosis and Hemostasis and the French Society of Anesthesia and Intensive Care . 18 High-flow nasal cannula oxygenation was initiated in patients requiring standard oxygen ≥ 9 L/min to maintain peripheral arterial oxygenation saturation ≥ 92%. The timing of intubation and mechanical ventilation was not protocolized but determined by the ICU team on a case-by-case basis. The exclusion criteria were: too high cycle threshold value in RT-PCR assay for variant screening; ARF due to 501Y.V1; and ARF due to 501Y.V3. Data collection and study outcomes Information was collected on the following: demographic characteristics; comorbidities; organ failure during ICU stay requiring venovenous extracorporeal membrane oxygenation, renal replacement therapy, invasive or non-invasive mechanical ventilation, use of catecholamines; prognosis (mechanical ventilation duration, length of stay in hospital and in ICU, and in-hospital and in-ICU mortality); and morbidity (coinfection, thromboembolic complications, and hospital-acquired pneumonia). The primary outcome was 28-day in-hospital mortality. The secondary outcomes were the occurrence of pulmonary embolism, the occurrence of hospital-acquired pneumonia, the need for venovenous extracorporeal membrane oxygenation support, and in-ICU length of stay. Statistical analysis Categorical variables were expressed as total number (percentages). Continuous variables were expressed as median [25 th - 75 th percentiles]. The study cohort was divided into patients infected with the 501Y.V2 variant and patients infected with the original strain. As the study was not randomized, unbalanced covariates could have introduced selection and confusion biases. Moreover, the number of covariates was large relative to the number of primary outcomes. These two problems were addressed by using a matching process based on a propensity score and a prognostic score in which one patient infected with the 501Y.V2 variant was matched with one patient infected with the original strain. 19,20 The propensity score was determined by fitting a logistic regression to estimate the probability of being infected with the 501Y.V2 variant. 21 The prognostic score was determined by fitting a logistic regression to estimate the probability of the primary outcome occurring in patients infected with the original strain (and unlikely to be infected with the 501Y.V2 variant since they were hospitalized between 13 March 2020 and 31 December 2020), and then by applying the generated model to the entire cohort. 22 Patients were matched based on the two scores using a Mahalanobis distance with a caliper width of 0.5. 19,20,23 No replacement was allowed, and all patients were matched only once. Baseline characteristics were compared before and after matching. Quantitative variables were compared using the Student’s t-test or Mann-Whitney U test, as appropriate. Qualitative variables were compared using the chi-square test or Fisher’s exact test, as appropriate. The marginal effect of being infected with the 501Y.V2 variant on the primary outcome (with 95% confidence interval) was estimated by applying the Doubly Robust Matching Estimator (DRME) on the matched cohort with proper control of confounding. 20 The advantage of this approach being that only one of the two score models needs to be correct to obtain a consistent estimator. 20 Lastly, the odds ratios of the primary and secondary outcomes (with 95% confidence intervals) were estimated using a conditional logistic regression. A P- value < 0.05 was considered significant. All analyses were performed at a two-tailed alpha level of 0.05. Statistical analyses were conducted with SAS 9.4 (SAS Institute, Cary, NC). Results Over the study period, 284 patients tested positive for SARS-CoV-2 were hospitalized in one of the two ICUs of Reunion Island University Hospital. Of these, 66 were excluded: 16 because they did not develop ARF, 5 had ARF due to 501Y.V1 variant and 45 because the cycle threshold values obtained in the RT-PCR assay were too high for variant of concern screening. The remaining 218 patients formed the cohort (Fig. 1 ). Matching resulted in two well-matched groups of 62 patients each (Fig. 1 ). Characteristics Of The 218 Pre-matched Patients Of the 218 pre-matched patients, 50 (22.9%) were transferred to Reunion Island from Mayotte or the Comoros. Patient characteristics on ICU admission are shown in Table 1 . In summary, 83 (38.1%) patients had ARF due to the 501Y.V2 variant. The median Simplified Acute Physiology Score was 32 [25–43], and the median number of days between the onset of symptoms and hospitalization in ICU was 8 [ 5 – 11 ] day. Patients infected with the 501Y.V2 variant were younger (58 [51–68] vs. 67 [56–74] years old, P = 0.003), had less hypertension (54.2% vs 68.1%, P = 0.04), and had less chronic kidney disease (13.3% vs. 31.9%, P = 0.002) than patients infected with the original strain (Table 1 ). Table 1 Baseline patient characteristics in pre-matched groups Variables Total 501Y.V2 P -value (n = 218) No (n = 135) Yes (n = 83) Delay between hospital admission and onset of symptoms (days) 5 [2.5-7] 5 [ 2 – 8 ] 5 [ 3 – 7 ] 0.29 Delay between in ICU admission and onset of symptoms (days) 8 [ 5 – 11 ] 8 [ 5 – 11 ] 7 [ 5 – 11 ] 0.59 Comorbidities Age (years old) 62 [53–73] 67 [56–74] 58 [51–68] 0.003 Male sex 139 (63.8) 81 (60) 58 (69.9) 0.11 Body mass index > 25 kg/m² 163 (74.8) 102 (75.6) 61 (73.5) 0.73 Cancer (< 3 months) 5 (2.3) 4 (3) 1 (1.2) 0.65 History of congestive heart failure 37 (17) 26 (19.3) 11 (11.3) 0.25 Diabetes mellitus 95 (43.6) 62 (45.9) 33 (39.8) 0.37 Hypertension 137 (62.8) 92 (68.1) 45 (54.2) 0.04 Chronic kidney disease 54 (24.8) 43 (31.9) 11 (13.3) 0.002 Chronic obstructive pulmonary disease 34 (15.6) 24 (17.8) 10 (12) 0.26 Immunodepression 19 (8.7) 13 (9.6) 6 (7.2) 0.54 During the first 24h in ICU Simplified Acute Physiology Score 2 32 [25–43] 34 [26–45] 31 [24–38] 0.29 High-fow oxygen therapy 194 (89) 120 (88.9) 74 (89.2) 0.99 Extent of lesions on initial CT scan > 50% 100 (45.9) 59 (45) 41 (49.4) 0.48 *Severe ARDS 49 (22.5) 27 (20) 22 (26.5) 0.32 Glasgow coma scale score 15 [ 15 – 15 ] 15 [ 15 – 15 ] 15 [ 15 – 15 ] 0.97 Enhanced thromboprophylaxis 215 (98.6) 132 (97.8) 83 (100) 0.55 Corticosteroids 185 (95.4) 116 (94.3) 69 (97.2) 0.49 Deworming with ivermectine 55 (27.9) 28 (23.1) 27 (35.5) 0.06 C-reactive protein (mg/L) 109 [69–177] 123 [73–187] 90 [68–169] 0.62 Creatinin (µmol/L) 93 [66–160] 95 [65–173] 90 [66–126] 0.04 D-dimer level (µg/mL) 1085 [609–2210] 1037 [602–1790] 1153 [693–3409] 0.3 Total bilirubin level (mg/dL) 12 [ 8 – 16 ] 12 [ 8 – 16 ] 14 [ 7 – 20 ] 0.83 Lactate dehydrogenase (IU/L) 470 [374–605] 498 [386–607] 444 [369–539] 0.3 Lymphocytes count (G/L) 0.8 [0.48–1.17] 0.8 [0.5–1.18] 0.78 [0.44–1.05] 0.4 Polynuclear neutrophils (G/L) 6.57 [4.33–9.76] 6.47 [4.54–8.98] 6.86 [4.13–10.59] 0.31 Fibrinogen (g/L) 6.1 [5.1–7.1] 6.1 [5.1–7.1] 5.9 [5.1–7.2] 0.61 Results are expressed as total numbers (percentages) for categorical variables and as medians [25th – 75th percentiles] for continuous variables as appropriate ARDS: acute respiratory distress syndrome; CT: computed tomography; ICU: intensive care unit *Defined as PaO2/FIO2 ratio ≤ 100 mmHg with PEEP ≥ 5 cm H2O Computed tomography scan showed severe pulmonary involvement (i.e. >50%) in 100 (45.9%) patients, with no difference between the two groups ( P = 0.48). A total of 194 (89%) patients received high-flow nasal cannula oxygenation on ICU admission. Forty-nine (22.5%) patients developed severe acute respiratory distress syndrome in the first 24 hours following admission. During ICU stay, 104 (47.7%) patients were intubated, of whom 101 (97.1%) received continuous neuromuscular blockade, 76 (73.1%) received prone position therapy, and 27 (26%) received nitric oxide. Moreover, 42 (19.3%) patients presented with acute kidney failure requiring renal replacement therapy, and 83 (38.1%) patients were treated with norepinephrine. Patients infected with the 501Y.V2 variant had a 28-day in-hospital mortality of 32.5%, compared to 22.2% for patients infected with the original strain ( P = 0.1). Characteristics And Prognosis Of The 124 Matched Patients After matching, there were no significant differences in characteristics between the group of patients infected with the 501Y.V2 variant and the group of patients infected with the original strain (Table 2 ). Table 2 Baseline patient characteristics in propensity-matched groups Variables Total 501Y.V2 variant Standardized difference (n = 124) No (n = 62) Yes (n = 62) Delay between hospital admission and onset of symptoms (days) 5.5 [ 3 – 8 ] 6 [ 3 – 10 ] 5 [ 3 – 7 ] 0.01 Delay between in ICU admission and onset of symptoms (days) 8 [ 5 – 11 ] 10 [ 5 – 12 ] 7 [ 5 – 10 ] -0.26 Comorbidities Age (years old) 60 [53–70] 61 [56–70] 60 [53–71] 0.01 Male sex 39 (31.5) 19 (30.6) 20 (32.3) -0.03 Body mass index > 25 kg/m² 93 (75) 48 (77.4) 45 (72.6) -0.11 Cancer (< 3 months) 4 (3.2) 3 (4.8) 1 (1.6) -0.18 History of congestive heart failure 21 (16.9) 11 (17.7) 10 (16.1) -0.04 Diabetes mellitus 46 (37.1) 24 (38.7) 22 (35.5) -0.07 Hypertension 64 (51.6) 32 (51.6) 32 (51.6) 0 Chronic kidney disease 21 (16.9) 10 (16.1) 11 (17.7) 0.04 Chronic obstructive pulmonary disease 16 (12.9) 10 (16.1) 11 (17.7) 0.04 Immunodepression 11 (8.9) 6 (9.7) 5 (8.1) -0.06 During the first 24h in ICU Simplified Acute Physiology Score 2 31 [24–42] 34 [24–46] 27 [24–37] -0.23 High-fow oxygen therapy 109 (87.9) 56 (90.3) 53 (85.5) -0.12 Extent of lesions on initial CT scan > 50% 63 56.8) 33 (62.3) 30 (51.7) -0.18 *Severe ARDS 32 (25.8) 15 (24.2) 17 (27.4) 0.06 Glasgow coma scale score 15 [ 15 – 15 ] 15 [ 15 – 15 ] 15 [ 15 – 15 ] -0.16 Enhanced thromboprophylaxis 124 (100) 62 (100) 62 (100) 0 Corticosteroids 106 (95.5) 53 (94.6) 53 (96.4) 0.08 Deworming with ivermectine 36 (31.9) 16 (29.6) 20 (33.9) 0.09 C-reactive protein (mg/L) 106 [69–171] 117 [73–176] 90 [69–168] -0.12 Creatinin (µmol/L) 82 [64–132] 78 [62–124] 87 [68–160] -0.12 D-dimer level (µg/mL) 969 [589–1915] 1271 [568–2393] 884 [589–1846] 0.43 Lactate dehydrogenase (IU/L) 448 [395–625] 512 [463–625] 445 [374–541] -0.16 Lymphocytes count (G/L) 0.83 [0.51–1.21] 0.8 [0.5–1.14] 0.84 [0.54–1.25] -0.17 Polynuclear neutrophils (G/L) 6.22 [4.07–9.97] 6.22 [4.3–10.6] 6.32 [3.97–9.71] 0.04 Fibrinogen (g/L) 6 [5.1–7.12] 6 [5.21–7.08] 6.5 [5.09–7.36] 0.14 Results are expressed as total numbers (percentages) for categorical variables and as medians [25th – 75th percentiles] for continuous variables as appropriate ARDS: acute respiratory distress syndrome; CT: computed tomography; ICU: intensive care unit *Defned as PaO2/FIO2 ratio ≤ 100 mmHg with PEEP ≥ 5 cm H2O Patients infected with the 501Y.V2 variant had significantly higher 28-day in-hospital mortality (30.6%) than patients infected with the original strain (19.4%, OR:2.4; 95%CI: 1.1–5.8 P = 0.04) (Fig. 2 ) (DRME: 0.12; 95%CI: 0.01–0.24). Pulmonary embolism occurred in 11 (17.7%) patients infected with the 501.YV2 variant and in 2 (3.2%) patients infected with the original strain ( P = 0.03). Hospital-acquired pneumonia occurred in 17 (43.6%) patients infected with the 501Y.V2 variant and in 8 (20.5%) patients infected with the original strain ( P = 0.03) (Table 3 ). Table 3 Outcome of the 124 matched patients during intensive care unit stay Variables Total 501Y.V2 variant *OR (95% CI) P -value (n = 124) No (n = 62) Yes (n = 62) Day-28 mortality 31 (25) 12 (19.4) 19 (30.6) 2.4 (1.1–5.8) 0.04 Pulmonary embolism 13 (10.5) 2 (3.2) 11 (17.7) 10 (1.3–78.2) 0.03 Hospital-acquired pneumonia 40 (32.3) 14 (22.6) 26 (41.9) 3 (1.2–7.6) 0.02 Extracorporeal membrane oxygenation 13 (10.5) 4 (6.5) 9 (14.5) 6 (0.7–49.8) 0.1 Renal replacement therapy 21 (16.9) 10 (16.1) 11 (17.7) 1.1 (0.4–3.1) 0.8 Prone position 48 (38.7) 23 (37.1) 25 (40.3) 1.2 (0.5–2.6) 0.68 Continuous neuromuscular blockers 59 (47.6) 27 (43.5) 32 (51.6) 1.6 (0.7–3.6) 0.3 Invasive mechanical ventilation 60 (48.4) 27 (43.5) 33 (53.2) 1.7 (0.7–3.8) 0.41 Nitric oxide 17 (13.7) 9 (14.5) 8 (12.9) 0.6 (0.2–1.9) 0.81 ICU lenght of stay (days) 10 [ 5 – 21 ] 10 [ 6 – 21 ] 9.5 [ 4 – 21 ] - 0.62 Results are expressed as total numbers (percentages) for categorical variables and as medians [25th – 75th percentiles] for continuous variables as appropriate ICU: intensive care unit; OR: odds ratio: CI: confidence interval *OR and 95%CI were estimated using univariate conditional logistic regression Doubly Robust Matching Estimator : 0.12 (95%CI: 0.01–0.24) The need for venovenous extracorporeal membrane oxygenation ( P = 0.1), and in-ICU length of stay were similar between the two groups ( P = 0.62) (Table 3 ). Discussion Our study is the first to compare the prognosis of patients with ARF due to the 501Y.V2 variant to that of patients with ARF due to the original strain. Patients infected with the 501Y.V2 variant had a 28-day in-hospital mortality of 32.5%, compared to 22.2% for patients infected with the original strain. This excess mortality was confirmed after matching for comorbidities and initial severity (30.6% vs. 19.4%, P = 0.04). These findings are unlikely to be the result of inadequate management of SARS-CoV-2 patients in our ICUs. Indeed, the SARS-CoV-2 epidemic took hold later and more slowly in Reunion Island than it did in Europe and the Americas. One consequence of this is that the local health care system, which meets European standards, never reached saturation. Another consequence is that we were able to draw on the experience of other health care centers in the management of SARS-CoV-2 patients. Right from the start, we privileged non-invasive ventilation over invasive ventilation (89% of patients on admission) 24 extensive use of corticosteroids (95.4% of patients), 17 and provided enhanced anticoagulation to reduce thromboembolic risk (98.6% of patients). 25 The adequate management of SARS-CoV-2 patients in Reunionese ICUs is confirmed by the fact that mortality observed in patients infected with the original strain is comparable to mortality rates reported in the recent literature. 24,26,27 Thus, the study by Kurtz et al . 24 found an in-ICU mortality of 31% in a cohort of 13,301 ICU patients infected with SARS-CoV-2, while that by Schmidt et al . reported a 28-day in-hospital mortality of 30% in a cohort of 4,244 patients. 26 Given these optimal management conditions, the excess mortality observed in our cohort is likely explained by the increased virulence of the 501Y.V2 variant relative to the original strain. This is supported by the fact that the number of recorded deaths due to SARS-CoV2 increased 2-fold in Reunion Island and 3-fold in Mayotte since the 501Y.V2 variant was first detected on these islands (January 2021). 2,13 Likewise, in South Africa, a preliminary analysis performed by the National Institute of Communicable Diseases found that mortality due to SARS-CoV2 was 20% higher during the second wave of the pandemic (when the majority of cases were due the 501Y.V2 variant) than during the first wave. 28 It should be noted that other variants were also found to be more virulent than the original strain. 29,30 In the United Kingdom, a retrospective study found a higher mortality of the 501Y.V1 variant compared to the original strain. 30 The excess mortality associated with the 501Y.V2 variant is especially worrying considering that our data were obtained when the local health care system was not saturated. As is the case with other SARS-CoV-2 variants, the 501Y.V2 variant appears to be more contagious than the original strain. 31–33 This means that saturation, a known risk factor for mortality, 34 could rapidly occur, with severe forms affecting patients who are younger and have less comorbidities. There is also a risk that the 501Y.V2 variant will undermine the vaccination campaign which is currently one of the pillars of the fight against SARS-CoV-2. The ChAdOx1 nCoV-19 Covid-19 vaccine, so far administered to approximately 3 million people in France, does not protect against medium to moderate infections by the 501Y.V2 variant. 8,35 Similarly, the Novavax vaccine is only 60% effective against this variant, 7 and other vaccines (AZD1222, NVX-CoV237, Ad26.COV2.S and BNT162b2) have shown lower efficacy in South Africa. 35 Our study has several limitations. Biases may have been introduced due to the retrospective nature of the study. In particular, a selection bias may have occurred as a significant proportion of patients infected with the 501Y.V2 variant were transferred from Mayotte, whose population is younger and presents fewer comorbidities than the Reunionese population. As randomization could not be achieved, we used a robust statistical methodology based on matching to minimize this bias. 20–23 In addition, mortality due to the 501Y.V2 variant was probably underestimated as several samples could not be screened for variants of concern. While our study sample may seem small (n = 218), it should be noted that all patients hospitalized in our two ICUs for ARF due to SARS-CoV-2 were evaluated, which also helped to reduce the selection bias. Moreover, patient management was the same in both ICUs, and unlike what was the case in many in other studies on the subject, it was optimal throughout the study period. 24,26 Conclusion In Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients infected with the 501Y.V2 variant than in patients infected with the original strain. These results are in line with reports on other SARS-CoV-2 variants of concerns, and should be considered in the future management of the pandemic. Abbreviations SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 ARF Acute respiratory failure ICU Intensive care unit RT-PCR Real-time reverse transcription-polymerase chain reaction DRME Doubly robust matching estimator Declarations Ethics approval, consent to participate and consent for publication The present observational study was approved by the Ethics Committee of the French Society of Infectious Disease and Tropical Medicine (CER-MIT 2021-N°00011642) and was declared to the Commission nationale de l’informatique et des libertés (French Data Protection Agency or CNIL MR004). All patients or their legally authorised representative were verbally informed and a written information notice was given about the process of data collection, for publication and could refuse to participate in the study. Availability of data and material The dataset used in the current study are available from the corresponding author. Competing interests: The authors declare that they have no competing interests. Funding This work was internally funded. Authors’ Contributions BP, AL, OS, had full access to all the study data and take responsibility for the completeness of the data and the accuracy of the analysis. Study concept and design: BP, AL, OS, CC, NA, CF, JA Acquisition of data : BP, AL, OS, CC, MCJ, MC, CV, PM, RB, YB, HB, JA, CF, NA, BP, AL, OS Analysis and interpretation of data: BP, AL, OS, CC, MCJ, MC, CV, PM, RB, YB, HB, JA, CF, NA, BP, AL, OS Drafting of the manuscript and critical revision of the manuscript for important intellectual content : BP, AL, OS, CC, MCJ, MC, CV, PM, RB, YB, HB, JA, CF, NA, BP, AL, OS Statistical analysis: JA, CF Funding : Support was provided solely by institutional and/or departmental sources. Administrative, technical and material support and study supervision: BP, AL, OS, CC, MCJ, MC, CV, PM, RB, YB, HB, JA, CF, NA, BP, AL, OS References Worobey, M. et al. 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G. et al. ;, Diaz-Ordaz K, Keogh R, Eggo RM, Funk S, Jit M, Atkins KE, Edmunds WJ. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science . 2021 Apr 9;372(6538):eabg3055. doi: 10.1126/science.abg3055 . Volz, E. et al. Evaluating the effect of SARS-CoV2 Spike mutation D614G on transmissibility et pathogenicity. Cell . 2021 Cell 2021 Jan7;184(1):64–75.e11. doi: 10.1016/j.cell.2020.11.020 . Pearson, C. A. B. et al. Estimates of severity and transmissibility of novel SARS-CoV-2 variant 501Y.V2 in South Africa (CMMID Repository, London, 2021). https:// cmmid.github.io/topics/covid19/sa-novel-variant.html Ji, Y., Ma, Z., Peppelenbosch, M. P. & Pan, Q. Potential association between COVID-19 mortality and health-care resource availability. Lancet Glob Health , 8 (4), e480 https://doi.org/10.1016/S2214-109X(20)30068-1 (2020 Apr). Karim, S. A. & de Oliveira, T. New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications. N Engl J Med , 384 (19), 1866–1868 https://doi.org/10.1056/NEJMc2100362 (2021). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 2 posted Editorial decision: Major revision 06 Apr, 2022 Reviews received at journal 30 Mar, 2022 Reviewers agreed at journal 11 Mar, 2022 Reviewers invited by journal 23 Nov, 2021 Editor assigned by journal 23 Nov, 2021 Editor invited by journal 20 Sep, 2021 Submission checks completed at journal 20 Sep, 2021 First submitted to journal 01 Sep, 2021 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-806080","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[{"code":1,"date":"2021-08-23 14:21:35","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research 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10:44:31","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-806080/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-806080/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":14187060,"identity":"0b4566fb-2a77-4b25-a8ee-f905eec1dc9e","added_by":"auto","created_at":"2021-10-01 14:33:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14938,"visible":true,"origin":"","legend":"Selection of the study sample","description":"","filename":"OnlineFigure1FLOWCHARTvariant.png","url":"https://assets-eu.researchsquare.com/files/rs-806080/v2/6696b18d9ccc94b91fb18024.png"},{"id":14187061,"identity":"551a2754-7e7c-452e-a63f-742212ca3869","added_by":"auto","created_at":"2021-10-01 14:33:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10193,"visible":true,"origin":"","legend":"Survival rate for the 124 matched patients (P=0.04)","description":"","filename":"Onlinefigure2kaplanmeier.png","url":"https://assets-eu.researchsquare.com/files/rs-806080/v2/4c8a873bced114fa75d19912.png"},{"id":14187081,"identity":"c6d2a1d3-ffb7-43d4-aaa9-0210226199f8","added_by":"auto","created_at":"2021-10-01 14:33:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":484788,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-806080/v2/2317bb19-4b50-4564-8cb7-b464afb4c050.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePrognosis of Critically Ill Patients With Acute Respiratory Failure Due To The SARS-CoV-2 501Y.V2 Variant: A Multicenter Retrospective Matched Cohort Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAn outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in China in December 2019 began to spread globally in January 2020.\u003csup\u003e1\u003c/sup\u003e Reunion Island (845,000 inhabitants), a French overseas department located in the Indian Ocean, was relatively spared by the SARS-CoV-2 pandemic until February 2021.\u003csup\u003e2\u003c/sup\u003e From the first detected case of SARS-CoV-2 infection on 19 March 2020 until 4 February 2021, only 10,330 cases and 5,4 deaths per 100,000 inhabitants were reported on the island.\u003csup\u003e2\u003c/sup\u003e These figures are likely due to the protective effects of climatic and environmental factors against SARS-CoV-2 transmission \u003csup\u003e3\u0026ndash;5\u003c/sup\u003e and to the geographical characteristics of Reunion Island (i.e. an insular territory with the international airport as its only entry point). To this is added the fact the local health care system meets European standards (16 extracorporeal membrane oxygenation supports, coronary angiography, all type of surgeries, etc.), and was therefore able to handle all cases without reaching saturation.\u003c/p\u003e \u003cp\u003eIn recent months, several SARS-CoV-2 variants of concern have been spreading worldwide. These are a source of worry as they may lead to: reinfection of SARS-CoV-2 recovered individuals;\u003csup\u003e6\u003c/sup\u003e lower effectiveness of vaccines;\u003csup\u003e7,8\u003c/sup\u003e a higher transmission rate;\u003csup\u003e9\u003c/sup\u003e and more severe pathogenicity.\u003csup\u003e9,10\u003c/sup\u003e The 501Y.V2 variant, which has three mutations to the spike protein, first appeared in the Eastern Cape Province of South Africa in October 2020 and then spread to other countries.\u003csup\u003e11,12\u003c/sup\u003e In Reunion Island, the first case of the 501Y.V2 variant was isolated on 4 January 2021 in a patient transferred from the Comoros for acute respiratory failure (ARF). Since then, the incidence of SARS-CoV-2 infection has increased 3-fold on the island.\u003csup\u003e2\u003c/sup\u003e In Mayotte, another French overseas department in the Indian Ocean, the incidence has increased 17-fold since the 501Y.V2 variant was first detected in January.\u003csup\u003e2,13\u003c/sup\u003e The 501Y.V2 variant is now the most common variant in Reunion Island, Mayotte, and the neighboring islands of the Comoros archipelago.\u003csup\u003e2,13\u003c/sup\u003e At present, no clinical data are available on the pathogenicity of ARF due to SARS-CoV-2 variant 501Y.V2. The aim of this study was to compare the prognosis of patients with ARF due to the 501Y.V2 variant to that of patients with ARF due to the original strain.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAll methods were performed in accordance with the French legislation on non-interventional studies. This study was registered with the National Institute of Health Data under the number MR4-04 (2206739) and approved by the Ethics Committee of the French Society of Infectious Disease and Tropical Medicine (CER-MIT 2021-N\u0026deg;00011642). Written and oral Informed Consent was obtained from all participants after they were given a written information notice about the process of data collection. All methods were performed in accordance with the relevant guidelines and regulations. This study complies with the Strengthening the Reporting of Observational studies in Epidemiology recommendations statement.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection of the study sample\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll consecutive patients with ARF due to SARS-CoV-2 who were hospitalized in one of the three intensive care units (ICUs) of Reunion Island University Hospital between 1 March 2020 and 18 April 2021 were included in the study ((F\u0026eacute;lix Guyon University Hospital, Saint-Pierre University hospital and Saint-Paul Hospital).\u003c/p\u003e\n\u003cp\u003eAcute respiratory failure was defined as bilateral pulmonary infiltrates on chest X-ray or computed tomography scan and need for\u0026nbsp;high-flow nasal cannula oxygenation or invasive\u0026nbsp;mechanical ventilation.\u003c/p\u003e\n\u003cp\u003eAll patients with\u0026nbsp;a\u0026nbsp;nasopharyngeal or respiratory\u0026nbsp;sample that tested positive\u0026nbsp;for SARS-CoV-2 by real-time reverse transcription-polymerase\u0026nbsp;chain reaction\u0026nbsp;(RT-PCR)\u0026nbsp;targeting the IP2 and IP4 regions and the N gene were evaluated. All positive samples were analyzed using NucliSens easyMAG system (BioM\u0026eacute;rieux).\u0026nbsp;From 1 January 2021 onwards, positive samples were also analyzed by\u0026nbsp;genome sequencing using Oxford Nanopore technology, as per the Artic Network\u0026rsquo;s overlapping amplicon protocol.\u003csup\u003e15,16\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic management\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with our protocol, all patients with ARF due to SARS-CoV-2 were treated with: (1) dexamethasone at a dosage of 6 mg/day for 10 days;\u003csup\u003e17\u003c/sup\u003e (2) deworming with ivermectine or albendazole; and (3) enhanced anticoagulation, as per the guidelines of the French Society of Thrombosis and Hemostasis and the French Society of Anesthesia and Intensive Care .\u003csup\u003e18\u003c/sup\u003e \u003c/p\u003e\n\u003cp\u003eHigh-flow nasal cannula oxygenation was initiated in patients requiring standard oxygen \u0026ge; 9 L/min to maintain peripheral arterial oxygenation saturation \u0026ge; 92%. The timing of intubation and mechanical ventilation was not protocolized but determined by the ICU team on a case-by-case basis.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were: too high cycle threshold value in RT-PCR assay for variant screening; ARF due to 501Y.V1; and ARF due to 501Y.V3. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and study outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformation was collected on\u0026nbsp;the following: demographic characteristics; comorbidities; organ failure\u0026nbsp;during ICU stay requiring venovenous extracorporeal membrane oxygenation,\u0026nbsp;renal replacement therapy, invasive\u0026nbsp;or\u0026nbsp;non-invasive\u0026nbsp;mechanical ventilation,\u0026nbsp;use of catecholamines; prognosis (mechanical ventilation duration, length of stay in hospital and in ICU, and in-hospital and in-ICU mortality);\u0026nbsp;and\u0026nbsp;morbidity (coinfection, thromboembolic complications,\u0026nbsp;and hospital-acquired pneumonia).\u003c/p\u003e\n\u003cp\u003eThe primary outcome was\u0026nbsp;28-day in-hospital mortality.\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes were the occurrence of pulmonary embolism, the occurrence of hospital-acquired pneumonia, the need for venovenous extracorporeal membrane oxygenation support, and in-ICU length of stay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCategorical variables were expressed as total number (percentages). Continuous variables were expressed as median [25\u003csup\u003eth\u003c/sup\u003e - 75\u003csup\u003eth\u003c/sup\u003e percentiles]. The study cohort was divided into patients infected with the 501Y.V2 variant and patients infected with the original strain. As the study was not randomized, unbalanced covariates could have introduced selection and confusion biases. Moreover, the number of covariates was large relative to the number of primary outcomes. These two problems were addressed by using a matching process based on a propensity score and a prognostic score in which one patient infected with the 501Y.V2 variant was matched with one patient infected with the original strain.\u003csup\u003e19,20\u003c/sup\u003e The propensity score was determined by fitting a logistic regression to estimate the probability of being infected with the 501Y.V2 variant.\u003csup\u003e21\u0026nbsp;\u003c/sup\u003eThe prognostic score was determined by fitting a logistic regression to estimate the probability of the primary outcome occurring in patients infected with the original strain (and unlikely to be infected with the 501Y.V2 variant since they were hospitalized between 13 March 2020 and 31 December 2020), and then by applying the generated model to the entire cohort.\u003csup\u003e22\u003c/sup\u003e Patients were matched based on the two scores using a Mahalanobis distance with a caliper width of 0.5.\u003csup\u003e19,20,23\u003c/sup\u003e No replacement was allowed, and all patients were matched only once. Baseline characteristics were compared before and after matching. Quantitative variables were compared using the Student\u0026rsquo;s t-test or Mann-Whitney U test, as appropriate. Qualitative variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. The marginal effect of being infected with the 501Y.V2 variant on the primary outcome (with 95% confidence interval) was estimated by applying the Doubly Robust Matching Estimator (DRME) on the matched cohort with proper control of confounding.\u003csup\u003e20\u003c/sup\u003e The advantage of this approach being that only one of the two score models needs to be correct to obtain a consistent estimator.\u003csup\u003e20\u003c/sup\u003e Lastly, the odds ratios of the primary and secondary outcomes (with 95% confidence intervals) were estimated using a conditional logistic regression. A \u003cem\u003eP-\u003c/em\u003evalue \u0026lt; 0.05 was considered significant. All analyses were performed at a two-tailed alpha level of 0.05. Statistical analyses were conducted with SAS 9.4 (SAS Institute, Cary, NC).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOver the study period, 284 patients tested positive for SARS-CoV-2 were hospitalized in one of the two ICUs of Reunion Island University Hospital. Of these, 66 were excluded: 16 because they did not develop ARF, 5 had ARF due to 501Y.V1 variant and 45 because the cycle threshold values obtained in the RT-PCR assay were too high for variant of concern screening. The remaining 218 patients formed the cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMatching resulted in two well-matched groups of 62 patients each (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch2\u003eCharacteristics Of The 218 Pre-matched Patients\u003c/h2\u003e\n\u003cp\u003eOf the 218 pre-matched patients, 50 (22.9%) were transferred to Reunion Island from Mayotte or the Comoros. Patient characteristics on ICU admission are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In summary, 83 (38.1%) patients had ARF due to the 501Y.V2 variant. The median Simplified Acute Physiology Score was 32 [25\u0026ndash;43], and the median number of days between the onset of symptoms and hospitalization in ICU was 8 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] day. Patients infected with the 501Y.V2 variant were younger (58 [51\u0026ndash;68] vs. 67 [56\u0026ndash;74] years old, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), had less hypertension (54.2% vs 68.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), and had less chronic kidney disease (13.3% vs. 31.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) than patients infected with the original strain (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristics in pre-matched groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e501Y.V2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;218)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;135)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelay between hospital admission and onset of symptoms (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 [2.5-7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 [\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 [\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelay between in ICU admission and onset of symptoms (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years old)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 [53\u0026ndash;73]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 [56\u0026ndash;74]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58 [51\u0026ndash;68]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58 (69.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u0026thinsp;\u0026gt;\u0026thinsp;25 kg/m\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163 (74.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (75.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (73.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer (\u0026lt;\u0026thinsp;3 months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of congestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (45.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137 (62.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (68.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunodepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring the first 24h in ICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimplified Acute Physiology Score 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 [25\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 [26\u0026ndash;45]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 [24\u0026ndash;38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-fow oxygen therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (89.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of lesions on initial CT scan\u0026thinsp;\u0026gt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (45.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (49.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Severe ARDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlasgow coma scale score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnhanced thromboprophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215 (98.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132 (97.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e185 (95.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116 (94.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69 (97.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeworming with ivermectine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (27.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109 [69\u0026ndash;177]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123 [73\u0026ndash;187]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 [68\u0026ndash;169]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinin (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 [66\u0026ndash;160]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 [65\u0026ndash;173]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 [66\u0026ndash;126]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer level (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1085 [609\u0026ndash;2210]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1037 [602\u0026ndash;1790]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1153 [693\u0026ndash;3409]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal bilirubin level (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e470 [374\u0026ndash;605]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e498 [386\u0026ndash;607]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e444 [369\u0026ndash;539]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes count (G/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8 [0.48\u0026ndash;1.17]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8 [0.5\u0026ndash;1.18]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.78 [0.44\u0026ndash;1.05]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolynuclear neutrophils (G/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.57 [4.33\u0026ndash;9.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.47 [4.54\u0026ndash;8.98]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.86 [4.13\u0026ndash;10.59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrinogen (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1 [5.1\u0026ndash;7.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.1 [5.1\u0026ndash;7.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9 [5.1\u0026ndash;7.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResults are expressed as total numbers (percentages) for categorical variables and as medians [25th \u0026ndash; 75th percentiles] for continuous variables as appropriate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eARDS: acute respiratory distress syndrome; CT: computed tomography; ICU: intensive care unit\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e*Defined as PaO2/FIO2 ratio\u0026thinsp;\u0026le;\u0026thinsp;100 mmHg with PEEP\u0026thinsp;\u0026ge;\u0026thinsp;5 cm H2O\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eComputed tomography scan showed severe pulmonary involvement (i.e. \u0026gt;50%) in 100 (45.9%) patients, with no difference between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.48).\u003c/p\u003e \u003cp\u003eA total of 194 (89%) patients received high-flow nasal cannula oxygenation on ICU admission. Forty-nine (22.5%) patients developed severe acute respiratory distress syndrome in the first 24 hours following admission. During ICU stay, 104 (47.7%) patients were intubated, of whom 101 (97.1%) received continuous neuromuscular blockade, 76 (73.1%) received prone position therapy, and 27 (26%) received nitric oxide. Moreover, 42 (19.3%) patients presented with acute kidney failure requiring renal replacement therapy, and 83 (38.1%) patients were treated with norepinephrine.\u003c/p\u003e \u003cp\u003ePatients infected with the 501Y.V2 variant had a 28-day in-hospital mortality of 32.5%, compared to 22.2% for patients infected with the original strain (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1).\u003c/p\u003e\n\u003ch2\u003eCharacteristics And Prognosis Of The 124 Matched Patients\u003c/h2\u003e\n\u003cp\u003eAfter matching, there were no significant differences in characteristics between the group of patients infected with the 501Y.V2 variant and the group of patients infected with the original strain (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristics in propensity-matched groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e501Y.V2 variant\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStandardized difference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelay between hospital admission and onset of symptoms (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 [\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelay between in ICU admission and onset of symptoms (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years old)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 [53\u0026ndash;70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 [56\u0026ndash;70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 [53\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (31.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u0026thinsp;\u0026gt;\u0026thinsp;25 kg/m\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (77.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (72.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer (\u0026lt;\u0026thinsp;3 months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of congestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunodepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring the first 24h in ICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimplified Acute Physiology Score 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 [24\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 [24\u0026ndash;46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 [24\u0026ndash;37]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-fow oxygen therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109 (87.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (85.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of lesions on initial CT scan\u0026thinsp;\u0026gt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 56.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (62.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Severe ARDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlasgow coma scale score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnhanced thromboprophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (95.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (94.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (96.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeworming with ivermectine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 [69\u0026ndash;171]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117 [73\u0026ndash;176]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 [69\u0026ndash;168]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinin (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 [64\u0026ndash;132]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 [62\u0026ndash;124]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87 [68\u0026ndash;160]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer level (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e969 [589\u0026ndash;1915]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1271 [568\u0026ndash;2393]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e884 [589\u0026ndash;1846]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e448 [395\u0026ndash;625]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e512 [463\u0026ndash;625]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e445 [374\u0026ndash;541]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes count (G/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 [0.51\u0026ndash;1.21]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8 [0.5\u0026ndash;1.14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.84 [0.54\u0026ndash;1.25]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolynuclear neutrophils (G/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.22 [4.07\u0026ndash;9.97]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.22 [4.3\u0026ndash;10.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.32 [3.97\u0026ndash;9.71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrinogen (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 [5.1\u0026ndash;7.12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 [5.21\u0026ndash;7.08]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.5 [5.09\u0026ndash;7.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResults are expressed as total numbers (percentages) for categorical variables and as medians [25th \u0026ndash; 75th percentiles] for continuous variables as appropriate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eARDS: acute respiratory distress syndrome; CT: computed tomography; ICU: intensive care unit\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e*Defned as PaO2/FIO2 ratio\u0026thinsp;\u0026le;\u0026thinsp;100 mmHg with PEEP\u0026thinsp;\u0026ge;\u0026thinsp;5 cm H2O\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients infected with the 501Y.V2 variant had significantly higher 28-day in-hospital mortality (30.6%) than patients infected with the original strain (19.4%, OR:2.4; 95%CI: 1.1\u0026ndash;5.8 \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (DRME: 0.12; 95%CI: 0.01\u0026ndash;0.24).\u003c/p\u003e\u003cp\u003ePulmonary embolism occurred in 11 (17.7%) patients infected with the 501.YV2 variant and in 2 (3.2%) patients infected with the original strain (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e \u003cp\u003eHospital-acquired pneumonia occurred in 17 (43.6%) patients infected with the 501Y.V2 variant and in 8 (20.5%) patients infected with the original strain (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcome of the 124 matched patients during intensive care unit stay\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e501Y.V2 variant\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e*OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay-28 mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.4 (1.1\u0026ndash;5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (1.3\u0026ndash;78.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital-acquired pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (1.2\u0026ndash;7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracorporeal membrane oxygenation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (0.7\u0026ndash;49.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal replacement therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1 (0.4\u0026ndash;3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProne position\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.2 (0.5\u0026ndash;2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContinuous neuromuscular blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.6 (0.7\u0026ndash;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive mechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.7 (0.7\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNitric oxide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6 (0.2\u0026ndash;1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU lenght of stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5 [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eResults are expressed as total numbers (percentages) for categorical variables and as medians [25th \u0026ndash; 75th percentiles] for continuous variables as appropriate\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eICU: intensive care unit; OR: odds ratio: CI: confidence interval\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e*OR and 95%CI were estimated using univariate conditional logistic regression\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eDoubly Robust Matching Estimator : 0.12 (95%CI: 0.01\u0026ndash;0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe need for venovenous extracorporeal membrane oxygenation (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1), and in-ICU length of stay were similar between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.62) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study is the first to compare the prognosis of patients with ARF due to the 501Y.V2 variant to that of patients with ARF due to the original strain. Patients infected with the 501Y.V2 variant had a 28-day in-hospital mortality of 32.5%, compared to 22.2% for patients infected with the original strain. This excess mortality was confirmed after matching for comorbidities and initial severity (30.6% vs. 19.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003eThese findings are unlikely to be the result of inadequate management of SARS-CoV-2 patients in our ICUs. Indeed, the SARS-CoV-2 epidemic took hold later and more slowly in Reunion Island than it did in Europe and the Americas. One consequence of this is that the local health care system, which meets European standards, never reached saturation. Another consequence is that we were able to draw on the experience of other health care centers in the management of SARS-CoV-2 patients. Right from the start, we privileged non-invasive ventilation over invasive ventilation (89% of patients on admission) \u003csup\u003e24\u003c/sup\u003e extensive use of corticosteroids (95.4% of patients),\u003csup\u003e17\u003c/sup\u003e and provided enhanced anticoagulation to reduce thromboembolic risk (98.6% of patients).\u003csup\u003e25\u003c/sup\u003e The adequate management of SARS-CoV-2 patients in Reunionese ICUs is confirmed by the fact that mortality observed in patients infected with the original strain is comparable to mortality rates reported in the recent literature.\u003csup\u003e24,26,27\u003c/sup\u003e Thus, the study by Kurtz \u003cem\u003eet al\u003c/em\u003e. \u003csup\u003e24\u003c/sup\u003e found an in-ICU mortality of 31% in a cohort of 13,301 ICU patients infected with SARS-CoV-2, while that by Schmidt \u003cem\u003eet al\u003c/em\u003e. reported a 28-day in-hospital mortality of 30% in a cohort of 4,244 patients.\u003csup\u003e26\u003c/sup\u003e Given these optimal management conditions, the excess mortality observed in our cohort is likely explained by the increased virulence of the 501Y.V2 variant relative to the original strain. This is supported by the fact that the number of recorded deaths due to SARS-CoV2 increased 2-fold in Reunion Island and 3-fold in Mayotte since the 501Y.V2 variant was first detected on these islands (January 2021).\u003csup\u003e2,13\u003c/sup\u003e Likewise, in South Africa, a preliminary analysis performed by the National Institute of Communicable Diseases found that mortality due to SARS-CoV2 was 20% higher during the second wave of the pandemic (when the majority of cases were due the 501Y.V2 variant) than during the first wave.\u003csup\u003e28\u003c/sup\u003e It should be noted that other variants were also found to be more virulent than the original strain.\u003csup\u003e29,30\u003c/sup\u003e In the United Kingdom, a retrospective study found a higher mortality of the 501Y.V1 variant compared to the original strain.\u003csup\u003e30\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe excess mortality associated with the 501Y.V2 variant is especially worrying considering that our data were obtained when the local health care system was not saturated. As is the case with other SARS-CoV-2 variants, the 501Y.V2 variant appears to be more contagious than the original strain.\u003csup\u003e31\u0026ndash;33\u003c/sup\u003e This means that saturation, a known risk factor for mortality,\u003csup\u003e34\u003c/sup\u003e could rapidly occur, with severe forms affecting patients who are younger and have less comorbidities. There is also a risk that the 501Y.V2 variant will undermine the vaccination campaign which is currently one of the pillars of the fight against SARS-CoV-2. The ChAdOx1 nCoV-19 Covid-19 vaccine, so far administered to approximately 3\u0026nbsp;million people in France, does not protect against medium to moderate infections by the 501Y.V2 variant.\u003csup\u003e8,35\u003c/sup\u003e Similarly, the Novavax vaccine is only 60% effective against this variant,\u003csup\u003e7\u003c/sup\u003e and other vaccines (AZD1222, NVX-CoV237, Ad26.COV2.S and BNT162b2) have shown lower efficacy in South Africa.\u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur study has several limitations. Biases may have been introduced due to the retrospective nature of the study. In particular, a selection bias may have occurred as a significant proportion of patients infected with the 501Y.V2 variant were transferred from Mayotte, whose population is younger and presents fewer comorbidities than the Reunionese population. As randomization could not be achieved, we used a robust statistical methodology based on matching to minimize this bias.\u003csup\u003e20\u0026ndash;23\u003c/sup\u003e In addition, mortality due to the 501Y.V2 variant was probably underestimated as several samples could not be screened for variants of concern. While our study sample may seem small (n\u0026thinsp;=\u0026thinsp;218), it should be noted that all patients hospitalized in our two ICUs for ARF due to SARS-CoV-2 were evaluated, which also helped to reduce the selection bias. Moreover, patient management was the same in both ICUs, and unlike what was the case in many in other studies on the subject, it was optimal throughout the study period.\u003csup\u003e24,26\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients infected with the 501Y.V2 variant than in patients infected with the original strain. These results are in line with reports on other SARS-CoV-2 variants of concerns, and should be considered in the future management of the pandemic.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSARS-CoV-2\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSevere acute respiratory syndrome coronavirus 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eARF\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute respiratory failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eICU\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRT-PCR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReal-time reverse transcription-polymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDRME\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDoubly robust matching estimator\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval, consent to participate and consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present observational study was approved by the Ethics Committee of the French Society of Infectious Disease and Tropical Medicine (CER-MIT 2021-N\u0026deg;00011642) and was declared to the Commission nationale de l\u0026rsquo;informatique et des libert\u0026eacute;s (French Data Protection Agency or CNIL MR004). All patients or their legally authorised representative were verbally informed and a written information notice was given about the process of data collection, for publication and could refuse to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset used in the current study are available from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was internally funded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBP, AL, OS,\u0026nbsp;had full access to all the study data and take responsibility for the completeness of the data and the accuracy of the analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStudy concept and design:\u003c/em\u003e BP, AL, OS, CC, NA, CF, JA\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcquisition of data\u003c/em\u003e:\u0026nbsp;BP, AL, OS, CC, MCJ, MC, CV,\u0026nbsp;PM,\u0026nbsp;RB,\u0026nbsp;YB, HB, JA, CF, NA,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBP, AL, OS\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAnalysis and interpretation of data:\u003c/em\u003e BP, AL, OS, CC, MCJ, MC, CV, PM, RB, YB, HB, JA, CF, NA,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBP, AL, OS\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDrafting of the manuscript and critical revision of the manuscript for important intellectual content\u003c/em\u003e:\u0026nbsp;BP, AL, OS, CC, MCJ, MC, CV,\u0026nbsp;PM,\u0026nbsp;RB,\u0026nbsp;YB, HB, JA, CF, NA,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBP, AL, OS\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis:\u003c/em\u003e JA, CF\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u003c/em\u003e Support was provided solely by institutional and/or departmental sources.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdministrative, technical and material support and study supervision:\u0026nbsp;\u003c/em\u003eBP, AL, OS, CC, MCJ, MC, CV,\u0026nbsp;PM,\u0026nbsp;RB,\u0026nbsp;YB, HB, JA, CF, NA,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBP, AL, OS\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorobey, M. \u003cem\u003eet al.\u003c/em\u003e The emergence of SARS-CoV-2 in Europe and North America. \u003cem\u003eScienc\u003c/em\u003ee; 2020 370(6516): 564\u0026ndash;570.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObservatoire de l'\u0026eacute;pid\u0026eacute;mie COVID-19 \u0026mdash; Open Data La R\u0026eacute;union. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://data.regionreunion.com/pages/dashboard-covid19/\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang, L-Q. \u003cem\u003eet al.\u003c/em\u003e Meteorological conditions and nonpharmaceutical interventions jointly determined local transmissibility of COVID-19 in 41 Chinese cities: A retrospective observational study. \u003cem\u003eLancet Reg Health - West Pac\u003c/em\u003e, 100020 https://doi.org/https://doi.org:10.106/j.lanwpc.2020.100020 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSajadi, M. 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New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications. \u003cem\u003eN Engl J Med\u003c/em\u003e, \u003cb\u003e384\u003c/b\u003e (19), 1866\u0026ndash;1868 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMc2100362\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2, COVID-19, 501Y.V2, Acute respiratory failure, acute respiratory distress syndrome","lastPublishedDoi":"10.21203/rs.3.rs-806080/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-806080/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe aim of this study was to compare the prognosis of patients with acute respiratory failure (ARF) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant 501Y.V2 to that of patients with ARF due to the original strain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective matched cohort study included all consecutive patients who were hospitalized for ARF due to SARS-CoV-2 in Reunion Island University Hospital between March 2020 and March 2021. Twenty-eight in hospital mortality was evaluated before and after matching.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 218 patients with ARF due to SARS-CoV-2 were enrolled in the study. Of these, 83 (38.1%) were infected with the 501Y.V2 variant. During intensive care unit stay, 104 (47.7%) patients received invasive mechanical ventilation and 20 (9.2%) patients were supported by venovenous extracorporeal membrane oxygenation. Patients infected with the 501Y.V2 variant were younger (58 [51\u0026ndash;68] vs. 67 [56\u0026ndash;74] years old, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), had less hypertension (54.2% vs 68.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), and had less chronic kidney disease (13.3% vs. 31.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) than patients infected with the original strain. After controlling for confounding variables (62 matched patients in each group), 28-day mortality was higher in the group of patients infected with the 501Y.V2 variant (30.6%) than in the group of patients infected with the original strain (19.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients with ARF infected with the 501Y.V2 variant than in patients infected with the original strain.\u003c/p\u003e","manuscriptTitle":"Prognosis of Critically Ill Patients With Acute Respiratory Failure Due To The SARS-CoV-2 501Y.V2 Variant: A Multicenter Retrospective Matched Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2021-10-01 14:33:30","doi":"10.21203/rs.3.rs-806080/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-04-07T03:49:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-03-31T01:56:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8bde3c40-ecc4-4d91-a936-30b44256f85b","date":"2022-03-11T14:39:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-11-23T17:43:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-11-23T17:42:30+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-09-20T11:42:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-09-20T11:33:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-09-01T07:13:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dffad6b3-c382-4ec4-83c4-c26474396186","owner":[],"postedDate":"October 1st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":7575898,"name":"Health Policy"},{"id":7575899,"name":"General Microbiology"},{"id":7575900,"name":"Virology"}],"tags":[],"updatedAt":"2022-05-12T04:59:14+00:00","versionOfRecord":[],"versionCreatedAt":"2021-10-01 14:33:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-806080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-806080","identity":"rs-806080","version":["v2"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}