Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study.

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2-5.2) in the H1N1 group and 7.2 (5.3-9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34-4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.

A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021.

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU.

COCARDE Study-Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study.

BACKGROUND: The effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. OBJECTIVE: The aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. METHODS: This prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. RESULTS: A total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. CONCLUSIONS: A better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. TRIAL REGISTRATION: Clinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24931.

Neglecting Plasma Protein Binding in COVID-19 Patients Leads to a Wrong Interpretation of Lopinavir Overexposure.

Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in coronavirus disease 2019 (COVID-19) are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in patients with severe COVID-19 than those reported in patients with HIV. These findings have led to a reduction of the dose of lopinavir in some patients, hypothesizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse University Hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin, and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In patients with COVID-19, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration, whereas the unbound concentration remains constant, and insufficient to reduce the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration.

Hydroxychloroquine in Coronavirus Disease 2019 Patients: What Still Needs to Be Known About the Kinetics.

Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.

Cardiac imaging phenotype in patients with coronavirus disease 2019 (COVID-19): results of the cocarde study.

Biological cardiac injury related to the Severe Acute Respiratory Syndrome Coronavirus-2 infection has been associated with excess mortality. However, its functional impact remains unknown. The aim of our study was to explore the impact of biological cardiac injury on myocardial functions in patients with COVID-19. 31 patients with confirmed COVID-19 (CoV+) and 16 controls (CoV-) were prospectively included in this observational study. Demographic data, laboratory findings, comorbidities, treatments and myocardial function assessed by transthoracic echocardiography were collected and analysed in CoV+ with (TnT+) and without (TnT-) elevation of troponin T levels and compared with CoV-. Among CoV+, 13 (42%) exhibited myocardial injury. CoV+/TnT + patients were older, had lower diastolic arterial pressure and were more likely to have hypertension and chronic renal failure compared with CoV+/TnT-. The control group was comparable except for an absence of biological inflammatory syndrome. Left ventricular ejection fraction and global longitudinal strain were not different among the three groups. There was a trend of decreased myocardial work and increased peak systolic tricuspid annular velocity between the CoV- and CoV + patients, which became significant when comparing CoV- and CoV+/TnT+ (2167 ± 359 vs. 1774 ± 521%/mmHg, P = 0.047 and 14 ± 3 vs. 16 ± 3 cm/s, P = 0.037, respectively). There was a decrease of global work efficiency from CoV- (96 ± 2%) to CoV+/TnT- (94 ± 4%) and then CoV+/TnT+ (93 ± 3%, P = 0.042). In conclusion, biological myocardial injury in COVID 19 has low functional impact on left ventricular systolic function.