Oral Isotretinoin and Covid-19 Infection

Does Oral Isotretinoin Increase the Risk of Developing Infection With and Complications From Covid-19, Compared to an Age-matched Background Population

There is a theoretical risk that the nasal mucosal dryness caused by oral retinoid medications may increase the risk of patients becoming infected with Covid-19.

Isotretinoin is a drug used commonly in dermatology, usually for management of acne and occasionally for management of other dermatological diseases. The most common side effect of oral isotretinoin is mucocutaneous dryness, which can lead to nasal dryness and crusting. Isotretinoin is derived from vitamin A and produces this side effect by arresting the cell cycle of mucus secreting cells in the nasal cavity. The mucus usually secreted moisturises the nasal cavity and provides a protective, lubricating layer overlying the cilia.

Cilia and nasal mucous are both believed to have roles in defence against infection and immunity. Hence it was postulated at the start of the pandemic that the effect this medication has on the nasal environment may increase the likelihood of contracting a disease spread by droplet or aerosol particles.

In March 2020 we established a departmental Excel database of our patients on oral retinoid medications in order to track those currently receiving treatment.

The database includes people taking isotretinoin, alitretinoin and acitretin. The greatest number of patients in this database are in the isotretinoin group and patients taking isotretinoin tend to be a relatively young and fit population. Acitretin on the other hand is often used in an older population who may have other underlying disease comorbidities. There were only a very small number of patients taking alitretinoin in the database.

In order to limit confounding variables and provide as clear a result as possible, it was decided to limit this study to comparing the group of patients taking isotretinoin, aged 16-40years, with an age-matched background population from NHS Grampian.

This study would examine the electronic patient record of patients aged 16-40years, taking isotretinoin between March and October 2020 and compare their rates of Covid-19 infection, hospitalisation and complications with the rates of the local age-matched background population. Persons taking isotretinoin in the time period would be excluded from the background population.

As Covid-19 is a new disease, the existing research literature on this specific topic is extremely limited, and so far this study would be the first in this area.

Study Overview

• Status: Unknown
• Conditions: Covid19; Isotretinoin Adverse Reaction

Detailed Description

Isotretinoin is a drug used commonly in dermatology, usually for management of acne and occasionally for management of other dermatological diseases. The most common side effect of oral isotretinoin is mucocutaneous dryness, which can lead to nasal dryness and crusting. Isotretinoin is derived from vitamin A and produces this side effect by arresting the cell cycle of mucus secreting cells in the nasal cavity. The mucus usually secreted moisturises the nasal cavity and provides a protective, lubricating layer overlying the cilia.

Cilia and nasal mucous are both believed to have roles in defence against infection and immunity. Hence it was postulated at the start of the pandemic that the effect this medication has on the nasal environment may increase the likelihood of contracting a disease spread by droplet or aerosol particles, such as Covid-19.

In March 2020 we established a departmental database of our patients on oral retinoid medications in order to track those currently receiving treatment. The database includes people taking isotretinoin, alitretinoin and acitretin. The greatest number of patients in this database are in the isotretinoin group and patients taking isotretinoin tend to be a relatively young and fit population. Acitretin on the other hand is often used in an older population who may have other underlying disease comorbidities. There were only a very small number of patients taking alitretinoin in the database.

In order to limit confounding variables and provide as clear a result as possible, it was decided to limit this study to comparing the group of patients taking isotretinoin, aged 16-40years, with an age-matched background population from NHS Grampian.

This study would examine the electronic patient record of patients aged 16-40years, taking isotretinoin between March and October 2020 and compare their rates of Covid-19 infection, hospitalisation and complications with the rates of the local age-matched background population. Persons taking isotretinoin in the time period would be excluded from the background population.

As Covid-19 is a new disease, the existing research literature on this specific topic is extremely limited, and so far this study would be the first in this area.

The electronic patient record of patients aged 16-40years taking isotretinoin between March and October 2020 will be accessed and the following will be recorded:

• Covid-19 testing while on or within 4 weeks after treatment
• Positive Covid-19 test while on or within 4 weeks after treatment
• Hospitalisation with Covid-19 while on or within 4 weeks after treatment
• ICU admission while on or within 4 weeks of treatment
• Death directly attributed to Covid-19 while on or within 4 weeks of treatment. The data held in the database is identifiable and held on the NHS Grampian secure server.

Once the details above are filled in each case will be anonymised with a case number. A key linking this back to the CHI will be kept on the NHS Grampian secure server.

Further data analysis will be completed using the anonymised data.

Details of an age matched local population can be obtained from Health Intelligence pending R&D approval of this study.

The University of Aberdeen department of medical statistics have already been consulted about this project and are willing to offer their help with data analysis. Once statistical analysis has been decided upon we will update the protocol or submit the details as an amendment, before analysis takes place.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Louise King; Email: researchgovernance@abdn.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is an estimate based on the number of patients taking isotretinoin aged 16-40 we have in the departmental database. We would try and obtain equal numbers in the isotretinoin and background populations as far as possible, roughly 125 patients who received isotretinoin and 125 background patients who did not. The numbers in each population can only be finally determined when the database is interrogated and details are obtained from Health Intelligence, neither of which can happen prior to approvals

Description

Inclusion Criteria:

• Test: prescribed oral isotretinoin in NHS Grampian age 16-40years includive, between March-Oct 2020

Background control population: residing in NHS Grampian, age 16-40years, etsted for Covid-19 between march -oct 2020, not prescribed oral isotretinoin in timeframe.

Exclusion Criteria:

• Test population: not prescribed oral isotretinoin in NHS grampian, outwith age range 16-40years or treatment range March-October 2020.

Background control popuat8ion: prescribed oral isotretinoin between march-october 2020, age outwith 16-40years, not tested for covid-19 between March-Oct 2020.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Isotretinoin; Test population, prescribed oral isotretinoin between March and October 2020.
Control; Background age-matched population, not prescribed oral isotretinoin during March to October 2020

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome	Did patients taking isotretinoin have a greater risk of infection with Covid-19 compared to an age-matched background population not taking isotretinoin.	March - October 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome	Did patients taking isotretinoin have a greater risk of hospitalisation related to Covid-19, ICU admission, or death from Covid-19, compared to an age-matched background population not taking isotretinoin	March - October 2020

Collaborators and Investigators

• Sponsor: University of Aberdeen

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2021
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): May 31, 2021

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Covid19; coronavirus; covid-19; isotretinoin
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 1/095/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Patient data will be reviewed bu study team only.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No