No Impact of Corticosteroid Use During the Acute Phase on Persistent Symptoms Post-COVID-19.

Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58-1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients.

Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients.

OBJECTIVES: Post-COVID-19 symptoms experienced by many survivors have a further devastating effect. This study aimed to analyze the risk factors associated with long COVID-19 in a prospective cohort of hospitalized patients including those requiring intensive care unit (ICU) transfer, taking into account objective measures of COVID-19 severity. METHODS: Hospitalized patients with confirmed COVID-19 were enrolled. A structured follow-up visit was performed 4 months after hospital admission. Multivariable adjusted regression models were used to analyse the association between parameters at the acute phase and persistent symptoms. RESULTS: A follow-up visit was performed in 316 patients including 115 (36.4%) discharged from the ICU. Mean age was 64.1 years, and 201 patients (58.3%) were men. Female sex (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.17-3.22; P =.01), hypertension (OR, 2.01; 95% CI, 1.22-3.31; P <.01), and the number of initial symptoms (NIS) (OR, 1.35; 95% CI, 1.17-1.54; P <.001) were significantly associated with long COVID-19. Number of persistent symptoms was significantly associated with NIS (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.11-1.22; P <.001), female sex (aIRR, 1.56; 95% CI 1.29-1.87; P <.001), hypertension (aIRR, 1.23; 95% CI, 1.02-1.50; P =.03), and length of stay in hospital (aIRR, 1.01; 95% CI, 1.005-1.017; P <.001). CONCLUSION: Our study suggested that female sex, hypertension, and NIS had a significant impact on persistent symptoms in hospitalized patients in contrast to severity of acute COVID-19 infection.

Plasma Markers of Neutrophil Extracellular Trap Are Linked to Survival but Not to Pulmonary Embolism in COVID-19-Related ARDS Patients.

Introduction: Coronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients. Here, we evaluate whether plasma levels of NET markers measured shorty after admission of hospitalized COVID-19 patients are associated with clinical outcomes in terms of clinical worsening, survival, and PE occurrence. Patients and Methods: Ninety-six hospitalized COVID-19 patients were included, 50 with ARDS (severe disease) and 46 with moderate disease. We collected plasma early after admission and measured 3 NET markers: total DNA, myeloperoxidase (MPO)-DNA complexes, and citrullinated histone H3. Comparisons between survivors and non-survivors and patients developing PE and those not developing PE were assessed by Mann-Whitney test. Results: Analysis in the whole population of hospitalized COVID-19 patients revealed increased circulating biomarkers of NETs in patients who will die from COVID-19 and in patients who will subsequently develop PE. Restriction of our analysis in the most severe patients, i.e., the ones who enter the hospital for COVID-19-related ARDS, confirmed the link between NET biomarker levels and survival but not PE occurrence. Conclusion: Our results strongly reinforce the hypothesis that NETosis is an attractive therapeutic target to prevent COVID-19 progression but that it does not seem to be linked to PE occurrence in patients hospitalized with COVID-19.

Mortality risk and antibiotic use for COVID-19 in hospitalized patients over 80.

INTRODUCTION: Patients over 80 years of age are more prone to develop severe symptoms and die from COVID-19. Antibiotics were massively prescribed in the first days of the pandemic without evidence of super infection. Antibiotics may increase the risk of mortality in cases of viral pneumonia. With age and antibiotic use, the microbiota becomes altered and less protective effect against lethal viral pneumonia. Thus we assessed whether it is safe to prescribe antibiotics for COVID-19 pneumonia to patients over 80 years of age. METHOD: We conducted a retrospective monocentric study in a 1240-bed university hospital. Our inclusion criteria were patients aged ≥ 80 years, hospitalized in a COVID-19 unit, with either a positive SARS-CoV-2 RT-PCR from a nasopharyngeal swab or a CT scan within 72 h after or prior to hospitalization in the unit suggestive of infection. RESULTS: We included 101 patients who received antibiotics and 48 who did not. The demographics in the two groups were similar. Overall mortality was higher for the group that received antibiotics than for the other group (36.6% vs 14.6%,). According to univariate COX analysis, the risk of mortality was higher (HR = 1.98 [0.926; 4.23]) but non-significantly for the antibiotic group. In multivariate analysis, independent risk factors of mortality were an increased leukocyte count and decreased oxygen saturation (HR = 1.097 [1.022; 1.178] and HR = 0.927 [0.891; 0.964], respectively). CONCLUSION: This study raises questions about the interest of antibiotic therapy, its efficacy, and its effect on COVID-19 and encourages further research.

Which features of an outpatient treatment for COVID-19 would be most important for pandemic control? A modelling study.

The global pandemic of coronavirus disease 2019 (COVID-19) has challenged healthcare systems worldwide. Lockdown, social distancing, and screening are thought to be the best means of stopping the virus from spreading and thus of preventing hospital capacity from being overloaded. However, it has also been suggested that effective outpatient treatment can control pandemics. We adapted a mathematical model of the beneficial effect of lockdown on viral transmission and used it to determine which characteristics of outpatient treatment would stop an epidemic. The data on confirmed cases, recovered cases, and deaths were collected from Santé Publique France. After defining components of the epidemic flow, we used a Morris global sensitivity analysis with a 10-level grid and 1000 trajectories to determine which of the treatment parameters had the largest effect. Treatment effectiveness was defined as a reduction in the patients' contagiousness. Early treatment initiation was associated with better disease control-as long as the treatment was highly effective. However, initiation of a treatment with a moderate effectiveness rate (5%) after the peak of the epidemic was still better than poor distancing (i.e. when compliance with social distancing rules was below 60%). Even though most of today's COVID-19 research is focused on inpatient treatment and vaccines, our results emphasize the potentially beneficial impact of even a moderately effective outpatient treatment on the current pandemic.

An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-ß-1a and hydroxychloroquine in hospitalized patients with COVID-19.

OBJECTIVES: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-ß-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. METHODS: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. RESULTS: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-ß-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-ß-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. CONCLUSION: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

Comparison of nasopharyngeal and saliva swabs for the detection of RNA SARS-CoV-2 during mass screening (SALICOV study).

In the context of a second wave of SARS-CoV-2 transmission, the use of saliva sampling has become an issue of real importance. SARS-CoV-2 RNA screening was performed on nasopharyngeal and saliva swabs collected from 501 individuals from residential homes for the elderly. The saliva samples were collected at the same time as the nasopharyngeal samples. Nasopharyngeal samples yielded positive results for 26 individuals, only two of whom also tested positive with saliva swabs. In this context, saliva collected by swabbing the fluid is not an ideal sample.

The association between body mass index class and coronavirus disease 2019 outcomes.

BACKGROUND/OBJECTIVES: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. SUBJECTS/METHODS: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. RESULTS: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. CONCLUSIONS: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

Trajectories of Hospitalization in COVID-19 Patients: An Observational Study in France.

Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p < 0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age: fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.

Trajectories of Hospitalization in COVID-19 Patients: An Observational Study in France

Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p <0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age: fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.

Abnormal laboratory findings and plasma concentration monitoring of lopinavir and ritonavir in COVID-19.

It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID-19 are concentration-dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID-19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430-20,842] ng/ml for lopinavir and 501 [247-891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r-treated patients with COVID-19.

Association between renin-angiotensin system inhibitors and COVID-19 complications.

AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays.

In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antibody detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.