key: cord-0901377-c9kqdf0m
authors: Montastruc, François; Romano, Charles; Montastruc, Jean-Louis; Silva, Stein; Seguin, Thierry; Minville, Vincent; Georges, Bernard; Riu-Poulenc, Béatrice; Fourcade, Olivier
title: Pharmacological characteristics of patients infected with SARS-Cov-2 admitted to Intensive Care Unit in South of France
date: 2020-05-15
journal: Therapie
DOI: 10.1016/j.therap.2020.05.005
sha: e7bc46f034680ddb6a54066f10cebbb030a71dba
doc_id: 901377
cord_uid: c9kqdf0m

nan

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can develop coronavirus disease 2019 (COVID-19), which drives many patients to hospital and some of them in intensive care units (ICUs). Little information is available about the main characteristics of patients admitted to hospital for COVID-19. A retrospective cohort study in hospitalized Chinese patients found that a majority of patients were men with a median age of 56 years and a 28% mortality rate [1] . Another recent US study in 5,700 patients found a median age of 63 years with mainly men (80.3%) and arterial hypertension (56.6%), obesity (41.7%) and diabetes (33.8%) as main comorbidities [2] . A case series of critically ill patients in Italy found that the majority were older men, requiring mechanical ventilation and high levels of positive end-expiratory pressure with 26% of mortality [3] .

Besides these demographical and clinical characteristics, there are relatively few data about drugs previously used in patients admitted to ICUs. Because some drugs could interact with the SARS-Cov-2 replication, some authors suggested that these drug exposures could be beneficial or harmful for COVID-19 patients. Among the pharmacological hypotheses, non-steroidal anti-inflammatory drugs (NSAIDs), drugs acting on the renin-angiotensin-aldosterone system (angiotensin converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARB] alias sartans) or incretin-based drugs (glucagon-like peptide-1 receptor agonists [GLP-1 agonists] and dipeptidyl peptidase 4 inhibitors [DDP-4 inhibitors]) were proposed as a potential factors modifying SARS-Cov-2 infectivity [4] [5] [6] . Therefore, there is an urgent need to assess what is the drug exposure of COVID-19 patients admitted to ICUs. Here, we described the demographics, baseline comorbidities, drug exposures and outcomes of the first COVID-19 patients admitted to Toulouse University Hospital ICUs.

This case series was conducted at Toulouse University Hospital in France between March 10, 2020 and April 21, 2020. All consecutive adult patients (≥18 years old) with nasal/throat swabs positive for SARS-CoV-2 by polymerase chain reaction admitted in the three intensive care units were included. Clinical outcomes were monitored until April 21, 2020, the final date of follow-up. Toulouse University Hospital institutional review board approved the project (n° RnIPH 2020-50).

Data were collected from the ICCA (IntelliSpace Critical Care and Anesthesia, Philips) and ORBIS (Agfa Healthcare) softwares, which record all medical informations in Toulouse University Hospital readmission during the study period, data from the first admission are presented.

We registered the main demographic, medical comorbidities and home medications of the patients upon entry to the ICU. Demographics, body mass index and comorbidities were available for all admitted patients. Home medications were reported based on the admission clinical examination. We collected outcomes including length of stay, invasive mechanical ventilation, discharge and mortality. Outcomes were not available for all patients at study end because they had not completed their ICU course. Data about medications after admission in ICUs were not registered (since it was not the goal of our study).

The results are presented in Table 1 .

During this 6-week period, 96 patients were admitted in intensive care units in Toulouse University Hospital. They were mainly men (79.2%) with mean age 63 years. We found that 87 patients (91%) have at least one comorbidity with a median value of 3. The most common comorbidities were overweight or obesity followed by arterial hypertension and diabetes mellitus. Drugs taken by the patients before hospital admission were mainly paracetamol followed by ARBs and metformin. Exposure to ACEIs was two times lower than that to ARBs.

During this period, 71 patients were intubated during their resuscitation stay, 70 left the unit and 9 deaths occurred. Deaths were observed in 6 men, mean age 68 years (range 36-88) after a mean follow-up in intensive care units of 7.3 days (range 2-19 days). All, except two who suffered from only overweight or obesity, had at least another previous medical history (1 patient with asthma, 1 pulmonary embolism, 1 dyslipidaemia plus myocardial infarction, 1 leukaemia, 1 arterial hypertension, 1 myeloma plus breast cancer, 1 bone dysplasia). Among patients who died in ICU, 3 patients were exposed to ARBs, 3 to corticosteroids or immunosuppressant drugs: none were exposed to ACEIs, NSAIDs or DDP4 inhibitors.

Overweight or obesity were found in 71.8% of patients intubated versus 50% patients without intubation. The rate of intubation for patients with hypertension not exposed to ACEI or ARB was 70%, 60% for patients with ACEIs and 95% with ARBs. The rate of intubation for patients with diabetes not exposed to DDP-4 inhibitors was 81% versus 43% for those exposed to DDP-4 inhibitors. Due to the small sample, no statistical analyses were performed.

The present study was performed to investigate the main clinical characteristics of COVID-19 patients admitted to ICU in Toulouse University Hospital (South Western, France) in March-April 2020 with a special focus on the main drugs received by the patients before admission. Several interesting points should be discussed. and metformin (1 patient out of 6). The fact that paracetamol was in first place before NSAIDs is probably explained by the campaign carried out at the beginning of the infection about the potential risks of NSAIDs (4) . Of course, due to the prevalence of cardiovascular diseases, ACEIs, ARBs, diuretics, beta-blocking agents and calcium channel inhibitors were widely found in this study. Among drugs acting on the reninangiotensin system, ARBs were prescribed twice as much as ACEIs. It is interesting to underline that no death was observed in patients treated by ACEIs. While in our sample of patients with hypertension, we found a higher rate of intubation among patients exposed to ARBs (95%) compared to patients with ACEIs (60%), no conclusion can be made. In fact, today, there is no clear evidence neither for a deleterious nor a favorable effect of ACEI/ARB in this situation. Several randomized trials are in course to examine more precisely these potent issues or benefits [5] .

In fact, we were unable to test putative statistical differences between the two groups as the power was to small and some confounding factors have to take into account in statistical analyses (age, sex, comorbidities). However, our observational study suggests potential differences between ARBs and ACEIs for the risk of intubation in COVID-19 patients. A recent observational study, involving patients who had been hospitalized in 11 countries on three continents, found that use of ACEIs may be associated with a lower risk of in-hospital death than non use (OR = 0.33, 95% CI, 0.20 to 0.54) while for ARBs, odds ratio J o u r n a l P r e -p r o o f 5 was 0.23 (95% CI, 0.87 to 1.74) versus non-use [8] . In addition in our sample of COVID-19 patients with diabetes, a lower rate of intubation was observed in patients treated by DPP4-inhibitors (43%) compared to those not exposed (81%).

The present work suffers from some mandatory shortcomings due to the collection method used.

Data were collected through software analysis and it was not possible to directly verify the data by interviewing patients directly since they were in the ICU. Our study is only a descriptive one. It is thus not possible to conclude about associated factors. This is particularly the case for smoking (only found in around 1 patient out of 16), for which a possible protective effect is currently discussed [9] . Since our work is a descriptive study, it also probably suffers from the indication bias (as well as for the lack of comparator). This work should be completed by other further investigations performed on larger French cohorts. However, this study, which reflects a particular situation in a university hospital in France, offers interesting perspectives for future research in the field of COVID-19 infection, particularly for future pharmacoepidemiological studies, since it is the first performed in France in such patients.

In conclusion, our study shows that patients admitted to intensive care units are mainly men suffering from overweight-obesity, arterial hypertension and chronically treated by cardiovascular drugs (more ARBs than ACEIs) and antihyperglycemic drugs.

Authors have no conflict of interest to declare. 7 a. The clinical outcomes were not available for 5 patients on the April 21, 2020, as they were still hospitalised.

b. There were less than 5 patients with auto-immune diseases, liver disease or depression * number of patients <5 ARBs: angiotensin II receptor blockers; ACEIs: angiotensin converting enzyme inhibitors; CCBs: calcium channel blockers; ICU: intensive care unit; PPIs: proton pump inhibitors. 

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Presenting characteristics, comorbidities and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region

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The authors acknowledge, first all other health care professionals in the intensive care unit who managed the patients, as well as Mrs Leila Chebane who helped to the collection of data.