Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus.

There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study.

COVID-19 Epidemic: Chloroquine, a French Obsession?

Introduction: One potential COVID-19 treatment, hydroxychloroquine has been the focus of much debate since its first publication by a French research team. To an unusual degree, this debate has extended outside of the medical community into the public sphere. Objective: To know if this interest, which conceals the reality of scientific debate, occurred worldwide. Methods: Methodological use of the Google-Trends was standardized. We researched the web queries for “hydroxychloroquine” and “chloroquine” and “amoxicillin” and “acetaminophen” as reference. Analysis was detailed by country. The relationship between these queries and the COVID-19 epidemic was supported by analysis of the main “related queries”. Google-Trends provided results on a relative value basis, on a scale from 0 to 100, with a value of 100 indicating the most researched criterion over the study period. Results: Web queries for “amoxicillin” never exceeded the value of 1. Searches for “acetaminophen” peaked on March 13 with a value of 13. “Hydroxychloroquine” was the most frequently researched term. It reached its peak value of 99 on April 7. Queries for “chloroquine” peaked (value 100) on March 24. Searches for “hydroxychloroquine” came essentially from Asia and the United States, with France in 22nd position (value of 21). Searches for “chloroquine” came essentially from Africa, with France in 8th position (value of 55). The five main related searches were in both cases associated with the COVID-19 epidemic. Conclusion: Interest in chloroquine is not specific to France. Results of ongoing studies have been and will be scrutinized attentively in all corners of the globe.

COVID-19 epidemic in the Seine-Saint-Denis Department of Greater Paris: one month and three waves for a tsunami.

INTRODUCTION: Worldwide, the COVID-19 epidemic has put health systems to the test. The excess mortality is partly due to the influx of patients requiring hospitalization and intensive care. We propose that the chronology of epidemic spread gives a window of time in which hospitals can act to prevent reaching capacity. METHODS: The out-of-hospital SAMU Emergency Medical System in an entry point into the French health care system. We recorded the number of patients managed, of patients transferred to emergency departments (ED), and of mobile intensive care units (MICUs) dispatched. Each criterion was compared to the mean of the same criterion over the previous 5 years. The alert threshold which indicated a public health crisis was defined as a 20% increase compared to the 5-year mean. RESULTS: The reference period, from January 2015 to December 2019, included 3 381 611 calls, and 1 137 856 patients. The study period, from 17 February to 28 March 2020, included 166 888 calls, and 56 708 patients. The daily numbers of patients managed crossed the threshold on February 25, and increased until the end of the study period. The daily number of patients transferred to ED crossed the threshold on March 16, and increased until the end of the period. The daily number of MICUs dispatched crossed the threshold on March 15, and increased until the end of the period. CONCLUSION: The COVID-19 epidemic reached our department in three consecutive waves which overwhelmed the health care system. The first wave preceded by 30 days the massive arrival of critical patients. Health care systems must take advantage of this delay to prepare for the third wave.

Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study.

Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear-nose-throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32-57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear-nose-throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear-nose-throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear-nose-throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent.