SARS-CoV-2 and Prevotella spp.: friend or foe? A systematic literature review.

During this global pandemic of the COVID-19 disease, a lot of information has arisen in the media and online without scientific validation, and among these is the possibility that this disease could be aggravated by a secondary bacterial infection such as Prevotella, as well as the interest or not in using azithromycin, a potentially active antimicrobial agent. The aim of this study was to carry out a systematic literature review, to prove or disprove these allegations by scientific arguments. The search included Medline, PubMed, and Pubtator Central databases for English-language articles published 1999-2021. After removing duplicates, a total of final eligible studies (n=149) were selected. There were more articles showing an increase of Prevotella abundance in the presence of viral infection like that related to Human Immunodeficiency Virus (HIV), Papillomavirus (HPV), Herpesviridae and respiratory virus, highlighting differences according to methodologies and patient groups. The arguments for or against the use of azithromycin are stated in light of the results of the literature, showing the role of intercurrent factors, such as age, drug consumption, the presence of cancer or periodontal diseases. However, clinical trials are lacking to prove the direct link between the presence of Prevotella spp. and a worsening of COVID-19, mainly those using azithromycin alone in this indication.

Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT).

OBJECTIVES: Nirmatrelvir in association with ritonavir (PAXLOVID™, Pfizer) is an antiviral agent targeting the 3-chymotrypsin-like cysteine protease enzyme (3C-like protease or Mpro) which is a key enzyme of the viral cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interactions in a polymedicated elected population for treatment. The aim of this work was to provide recommendations on behalf of the national French society of pharmacology (French Society of Pharmacology and Therapeutics; SFPT), by suggesting optimal and pragmatic therapeutic strategies if nirmatrelvir/ritonavir is to be given together with drugs commonly used, in order to ensure secured physicians' prescription. METHODS: Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommendations and proposed modifications. The final draft was then validated by all 18 participants. RESULTS: Five distinct recommendations were issued: i) contra-indications, ii) "PAXLOVID™ not recommended with the comedication", iii) "PAXLOVID™ possible whether the comedication is discontinued", iv) "PAXLOVID™ possible only after an expert advice" and v) "PAXLOVID™ possible without modification of the associated treatment". The final document comprises recommendations for 171 drugs/therapeutic classes aiming to secure prescription. In complex situations, clinicians are advised to contact their pharmacology department to obtain specific recommendations on the management of drug-drug interactions with nirmatrelvir/ritonavir. CONCLUSION: These recommendations intend to be a help for clinicians willing to prescribe nirmatrelvir/ritonavir and to prevent drug-drug interactions leading to adverse drug reactions or loss of efficacy. They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice.

COVID-19 vaccine hesitancy among healthcare workers.

OBJECTIVE: To characterize healthcare workers' (HCWs) intention to receive the COVID-19 vaccine by the beginning of the vaccine campaign in France. METHODS: Data were collected on a self-administered questionnaire through the website of a tertiary care center (February 9-18, 2021). RESULTS: Among 1,965 respondents, 1,436 (73.1%), 453 (23.1%), and 76 (3.9%) declared themselves in favor, hesitant, or against the COVID-19 vaccine: <60% of auxiliary nurses and technicians intended to be vaccinated, as compared to 60-79% of nurses and support staff, and>80% of medical staff. On multivariate analysis, age, occupation, flu vaccine history, and controversy over the AstraZeneca vaccine tolerability were independently associated with COVID-19 vaccine intention. CONCLUSIONS: Patterns of vaccine hesitancy related to the COVID-19 and influenza vaccines are similar among HCWs. Media communication on vaccine side effects have a dramatic effect on vaccine hesitancy. Efforts are requested to inform HCWs about the risk/benefit balance of COVID-19 vaccines.

Chronic use of renin-angiotensin-aldosterone system blockers and mortality in COVID-19: A multicenter prospective cohort and literature review.

AIMS: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19 and explored reasons for discrepancies in the literature. METHODS AND RESULTS: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement. CONCLUSION: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta-analyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.

Association of Antihypertensive Agents with the Risk of In-Hospital Death in Patients with Covid-19.

PURPOSE: The role of angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), or other antihypertensive agents in the case of Covid-19 remains controversial. We aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19. METHODS: We performed a retrospective multicenter cohort study on patients hospitalized between February 1 and May 15, 2020. All patients had been followed up for at least 30 days. RESULTS: Of the 8078 hospitalized patients for Covid-19, 3686 (45.6%) had hypertension and were included in the study. In this population, the median age was 75.4 (IQR, 21.5) years and 57.1% were male. Overall in-hospital 30-day mortality was 23.1%. The main antihypertensive pharmacological classes used were calcium channel blockers (CCB) (n=1624, 44.1%), beta-blockers (n=1389, 37.7%), ARB (n=1154, 31.3%), and ACEi (n=998, 27.1%). The risk of mortality was lower in CCB (aOR, 0.83 [0.70-0.99]) and beta-blockers (aOR, 0.80 [0.67-0.95]) users and non-significant in ARB (aOR, 0.88 [0.72-1.06]) and ACEi (aOR, 0.83 [0.68-1.02]) users, compared to non-users. These results remain consistent for patients receiving CCB, beta-blocker, or ARB as monotherapies. CONCLUSION: This large multicenter retrospective of Covid-19 patients with hypertension found a reduced mortality among CCB and beta-blockers users, suggesting a putative protective effect. Our findings did not show any association between the use of renin-angiotensin-aldosterone system inhibitors and the risk of in-hospital death. Although they need to be confirmed in further studies, these results support the continuation of antihypertensive agents in patients with Covid-19, in line with the current guidelines.

Potential drug-drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments.

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.