Is France Once Again Looking for a Scapegoat?

On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with "endangering the lives of others". It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.

Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?

Broadly neutralizing antibodies directed against human immunodeficiency virus (HIV) offer promise as long-acting agents for prevention and treatment of HIV. Progress and challenges are discussed. Lessons may be learned from the development of monoclonal antibodies to treat and prevent COVID-19.

Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications.

The coronavirus disease 2019 (COVID-19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug-metabolizing enzyme cytochrome P450 (CYP) 3A4. Thus nirmatrelvir/ritonavir, even given as a short treatment course, has a high potential to cause harm from drug-drug interactions (DDIs) with other drugs metabolized through this pathway. Options for mitigating risk from DDIs with nirmatrelvir/ritonavir are limited due to the clinical illness, the short window for intervention, and the related difficulty of implementing clinical monitoring or dosage adjustment of the comedication. Pragmatic options are largely confined to preemptive or symptom-driven pausing of the comedication or managing any additional risk through counseling. This review summarizes the effects of ritonavir on drug disposition (i.e., metabolizing enzymes and transporters) and discusses factors determining the likelihood of having a clinically significant DDI. Furthermore, it provides a comprehensive list of comedications likely to be used in COVID-19 patients which are categorized according to their potential DDI risk with nirmatrelvir/ritonavir. It also discusses recommendations for the management of DDIs which balance the risk of harm from DDIs with a short course of ritonavir, against unnecessary denial of nirmatrelvir/ritonavir treatment.

Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.

Preparing for future waves and pandemics: a global hospital survey on infection control measures and infection rates in COVID-19.

A survey of hospitals on three continents was performed to assess their infection control preparedness and measures, and their infection rate in hospital health care workers during the COVID-19 pandemic. All surveyed hospitals used similar PPE but differences in preparedness, PPE shortages, and infection rates were reported.

Viral Load Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Individuals With Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kinetics remain understudied, including the impact of remdesivir. In hospitalized individuals, peak sputum viral load occurred in week 2 of symptoms, whereas viremia peaked within 1 week of symptom-onset, suggesting early systemic seeding of SARS-CoV-2. Remdesivir treatment was associated with faster viral decay.

SARS-CoV-2 RNA Detection by a Cellphone-Based Amplification-Free System with CRISPR/CAS-Dependent Enzymatic (CASCADE) Assay.

CRISPR (Clustered regularly interspaced short palindromic repeats)-based diagnostic technologies have emerged as a promising alternative to accelerate delivery of SARS-CoV-2 molecular detection at the point of need. However, efficient translation of CRISPR-diagnostic technologies to field application is still hampered by dependence on target amplification and by reliance on fluorescence-based results readout. Herein, an amplification-free CRISPR/Cas12a-based diagnostic technology for SARS-CoV-2 RNA detection is presented using a smartphone camera for results readout. This method, termed Cellphone-based amplification-free system with CRISPR/CAS-dependent enzymatic (CASCADE) assay, relies on mobile phone imaging of a catalase-generated gas bubble signal within a microfluidic channel and does not require any external hardware optical attachments. Upon specific detection of a SARS-CoV-2 reverse-transcribed DNA/RNA heteroduplex target (orf1ab) by the ribonucleoprotein complex, the transcleavage collateral activity of the Cas12a protein on a Catalase:ssDNA probe triggers the bubble signal on the system. High analytical sensitivity in signal detection without previous target amplification (down to 50 copies µL-1) is observed in spiked samples, in ≈71 min from sample input to results readout. With the aid of a smartphone vision tool, high accuracy (AUC = 1.0; CI: 0.715 - 1.00) is achieved when the CASCADE system is tested with nasopharyngeal swab samples of PCR-positive COVID-19 patients.

COVID-19 and HIV infection co-pandemics and their impact: a review of the literature.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.

Mobile Health (mHealth) Viral Diagnostics Enabled with Adaptive Adversarial Learning.

Deep-learning (DL)-based image processing has potential to revolutionize the use of smartphones in mobile health (mHealth) diagnostics of infectious diseases. However, the high variability in cellphone image data acquisition and the common need for large amounts of specialist-annotated images for traditional DL model training may preclude generalizability of smartphone-based diagnostics. Here, we employed adversarial neural networks with conditioning to develop an easily reconfigurable virus diagnostic platform that leverages a dataset of smartphone-taken microfluidic chip photos to rapidly generate image classifiers for different target pathogens on-demand. Adversarial learning was also used to augment this real image dataset by generating 16,000 realistic synthetic microchip images, through style generative adversarial networks (StyleGAN). We used this platform, termed smartphone-based pathogen detection resource multiplier using adversarial networks (SPyDERMAN), to accurately detect different intact viruses in clinical samples and to detect viral nucleic acids through integration with CRISPR diagnostics. We evaluated the performance of the system in detecting five different virus targets using 179 patient samples. The generalizability of the system was confirmed by rapid reconfiguration to detect SARS-CoV-2 antigens in nasal swab samples (n = 62) with 100% accuracy. Overall, the SPyDERMAN system may contribute to epidemic preparedness strategies by providing a platform for smartphone-based diagnostics that can be adapted to a given emerging viral agent within days of work.

SARS-CoV-2 viral load is associated with increased disease severity and mortality.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.