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.

Hospital-wide SARS-CoV-2 antibody screening of 4840 staff members in a University Medical Center in France: a cross-sectional study.

OBJECTIVES: Healthcare workers are more likely to be infected by SARS-CoV-2. In order to assess the infectious risk associated with working in a hospital, we sought to estimate the proportion of healthcare professionals infected with SARS-CoV-2 by screening staff in a University Medical Center in France. SETTING: A hospital-wide screening campaign (comprising a serological test and a questionnaire) ran from 18 May to 26 July 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The seroprevalence rate was analysed in a multivariate analysis according to sociodemographic variables (age, sex and profession), exposure to SARS-CoV-2 and symptoms. RESULTS: A total of 4840 professionals were included, corresponding to 74.5% of the centre's staff. The seroprevalence rate (95% CI) was 9.7% (7.0% to 12.4%). Contact with a confirmed case of COVID-19 was significantly associated with seropositivity (OR (95% CI: 1.43, (1.15 to 1.78)). The seroprevalence rate was significantly higher among nursing assistants (17.6%) than among other healthcare professionals. The following symptoms were predictive of COVID-19: anosmia (OR (95% CI): 1.55, (1.49 to 1.62)), ageusia (1.21, (1.16 to 1.27)), fever (1.15, (1.12 to 1.18)), myalgia (1.03, (1.01 to 1.06)) and headache (1.03, (1.01 to 1.04)).

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.

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.

COVID-19 serology in nursing homes and long-term care facilities: prevalence of seroconversion in the Amiens-Picardie University Hospital.

INTRODUCTION: Since December 2019, an emerging infectious viral disease triggered by SARS-CoV-2 has caused a global pandemic. Elderly people, being more fragile, are the most affected by the severity and lethality of this disease. The residential care facility for dependent elderly people (Ehpad) and the long-term care facilities at the Amiens University Hospital registered their first COVID-19 cases in February 2020, which lead to the opening of a dedicated COVID-19 unit and aspecific protocol for isolation. METHODS: This descriptive study analysed the prevalence of COVID-19 seroconversion within the Ehpad and the long-term care facilities at the Amiens University Hospital. Both this screening test and the nasopharyngeal swab PCRs were used to assess the impact of the COVID-19 epidemic on the residents of the Ehpad and the long-term care facilities. RESULTS: On 15 and 16 June 2020, the serological tests for COVID-19 were positive for 146 (66.1%) of the residents tested. The seroconversion rate was significantly different (p < 0.001) between the Ehpad (88.7%) and the long-term care facility (45.6%). DISCUSSION: During the epidemic, there was no excess mortality index within the Ehpad and the long-term care facility services of the Amiens University Hospital. Among frail patients, the role of immunosenescence can be evoked to account for the absence of this inflammatory reaction. This study showed that isolating the infected patient in a dedicated unit significantly reduces the risk of seroconversion and contamination compared to isolating them within their own unit.

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.

[Covid-19 serology in nursing home and long-term care: prevalence of seroconversion in the Amiens-Picardie University Hospital]. / Sérologie Covid-19 en Ehpad et soins de longue durée : prévalence de la séroconversion au CHU Amiens-Picardie.

Since December 2019, an emerging infectious viral disease implicating a coronavirus SARS-CoV-2 has caused a global pandemic. Elderly people, being more fragile, are the most affected by the severity and lethality of this disease. The NH and LTCU of the Amiens University Hospital registered their first Covid-19 cases in February 2020, which lead to the opening of a Covid-19 dedicated unit and of specific protocol for confinement. This descriptive study was analyzing the prevalence of Covid-19 seroconversion within the NH and the LTCU of the Amiens University Hospital. Both this screening test and the nasopharyngeal swab PCRs were in order to assess the impact of the Covid-19 epidemic in NH and LTCU. On June 15th and 16th, the serological tests for Covid-19 were positive for 146 (66.1%) of the residents tested. The seroconversion rate was significantly different (p < 0.001) between the NH (88.7%) and the LTCU (45.6%). During the epidemic, there was no excess mortality index within the NH and LTCU services of the Amiens University Hospital. Among frail patients, the role of immunosenescence can be discussed to account for the absence of this inflammatory reaction. This study showed that isolating the infected patient in a dedicated unit significantly reduces the risk of seroconversion and contamination compared to isolating them within their own unit.

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.

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals.

A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.

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.