Clinical Outcomes after Use of Inhaled Corticosteroids or Oral Steroids in a COVID-19 Telemedicine Clinic Cohort: Retrospective Chart Review
Abstract
We identified patients with coronavirus disease 2019 that were followed by a telemedicine clinic and eventually referred to a post COVID clinic due to persistent symptoms of COVID-19. Of those patients requiring referral to the post COVID clinic, equal percentages of patients treated acutely with inhaled corticosteroids (ICS) and/ or oral steroids required referral to a pulmonary specialist. (Preprint)
Authors: Cellai Michele 
Published: December 2021

BACKGROUND

Introduction
The global pandemic caused by SARS-CoV-2 resulting in COVID-19 illness has resulted in significant morbidity and mortality all around the world. Millions have recovered from COVID-19 worldwide despite the limited treatment options in both the inpatient and outpatient settings. Concern remains among healthcare providers that although 80% of patients that contract COVID-19 are not hospitalized, there are few outpatient treatment options and we do not know how to prevent persistent symptoms.
While treatments for COVID-19 in hospitalized patient have been developed from repurposed medications such as remdesivir,[1] treatments on the outpatient side have been difficult to identify. Treatment has focused on mitigation of symptoms. Research into the use of dexamethasone in hospitalized patients with moderate to severe COVID-19 does show benefit; however, dexamethasone is not recommended for use in the outpatient setting in mild to moderate cases of COVID 19 not requiring oxygen support as research showed potential harm.[2] To date, the only approved treatment for COVID-19 in the outpatient setting is the use of monoclonal antibody therapy. This highlights the challenge of treating patients in the outpatient realm.
The inflammatory response to SARS-CoV-2 appears to contribute significantly to morbidity and mortality.[3] Corticosteroids are potent anti-inflammatory medications that suppress inflammation but can also suppress the immune system.[4] Inhaled corticosteroids (ICS) reduce inflammation, swelling, and mucous production in the lungs. Further investigation into how the use of corticosteroids might modify the outcome of SARS-CoV-2 infection and development of prolonged COVID-19 symptoms is needed. New research into the use of ICS after COVID-19 diagnosis showed that early administration of inhaled budesonide improved outcomes by reducing the likelihood of needing urgent medical care as well as reducing time to recovery after early COVID-19.[5] Additionally there was a relative reduction of 91% of clinical deterioration in the study patients receiving ICS. Therefore, evaluation of the use of ICS in the treatment of outpatient COVID-19 and long-term outcomes is advised.

OBJECTIVE

To determine if prescribing ICS or oral corticosteroids in the acute or subacute phase of COVID-19 altered long term outcome from COVID-19

METHODS

Methods
We conducted a retrospective chart review of the patients newly enrolled in the Emory Virtual Outpatient Management Clinic (VOMC) for non-hospitalized adult patients with nasopharyngeal sampling confirmed COVID-19 in Atlanta, Georgia between June 1 and December 31, 2020. Inclusion criteria included: (1) enrollment in telemedicine clinic within 28 days of a positive COVID-19 test (nasopharyngeal polymerase chain reaction), (2) specific symptom onset date recorded at the time of enrollment. Exclusion criteria included: (1) hospitalization prior to telemedicine clinic enrollment, and (2) hospitalization after enrollment during which the patient was treated with anti-viral medication and steroids.
Chart review included: (1) verification of patient demographics (2) verification of symptom onset dates (from screening clinic note and telemedicine clinic enrollment note), (3) review of follow-up notes with pulmonary division/ post-COVID clinic. Charts were reviewed through April 30, 2021, to evaluate for future referral to post-COVID clinic as well.
Patients with chronic steroid use (10 in total) were excluded from the post COVID-19 clinic referral evaluation as the goal was to review acute steroid use outcomes. Descriptive statistics were calculated using StataSE 16 software (College Station, TX).

RESULTS

Results
During the specified period, a total of 1167 VOMC new enrollment unique patient visits were identified who met inclusion criteria. There were 805 females (67%) and 362 males (Table 1). Average age was 48.54 years (range 18-96). Overall, 9.6% of patients had pre-existing asthma (n=112) (slightly more than the U.S. average of 8%); 0.9% had COPD (n=10) (less than the US average of 3.8%); and 3.1% had other lung diseases (n=36). Unfortunately, information on pre-existing conditions was missing for approximately one-third of the cohort, so these averages may be skewed.

Table 1. Characteristics of COVID-19 VOMC patients
Demographics	N (%) or Mean (SD)
Age { Mean (SD) Median [Range]}	48.54 (15.62) 49 [18,96]
Age (Categories)
18-29	152 (12.97)
30-39	215 (18.34)
40-49	249 (21.25)
50-59	243 (20.73)
60-69	192 (16.38)
70-79	87 (7.42)
>=80	34 (2.9)
Sex
Female	805 (68.98)
Male	362 (31.02)
Past Medical History
Asthma	112 (19.68)
COPD	10 (1.87)
Lung Disease	36 (6.68)
Acute Steroid Rx history
ICS	128 (10.92)
Oral CS	112 (9.56)
Chronic Steroid Rx history
ICS	6 (0.51)
Oral CS	4 (0.34)
None	1,162 (99.15)

N = 1167 patients seen in the Emory Healthcare Virtual Outpatient Management Clinic from 6/1/2020–12/31/2020.

A total of 63 (5.4%) patients were newly prescribed ICS and 63 (5.4%) patients were prescribed oral glucocorticoids (Table 2). Respectively, 20 and 19 patients from each group were referred to the post COVID-19 clinic due to persistent COVID-19 symptoms as of April 30, 2021.

Table 2. Acute steroid use and post-COVID clinic follow up

Acute ICS	Post-COVID clinic visit
No	Yes	Total
No	996	43	1,039
Yes	108	20	128
Total	1,104	63	1,167
Acute Oral CS	Post-COVID clinic visit
No	Yes	Total
No	1011	44	1,055
Yes	93	19	112
Total	1,104	63	1,167

N = 1167 patients seen in the Emory Healthcare Virtual Outpatient Management Clinic from 6/1/2020–12/31/2020.

CONCLUSIONS

Discussion
Our data demonstrates that an equal number of patients prescribed ICS versus oral steroids were eventually referred to the post-COVID-19 clinic. The 126 patients (10.8%) requiring referral for persistent symptoms due to COVID-19 are consistent with previously published data indicating 8-30% of people that contracted COVID-19 and were not hospitalized continued to have symptoms 6 months later.[6,7]
Future directions
Future studies into the treatment of COVID-19 symptom mitigation and reduction of long-term sequelae should include standardized dosing regimens for oral and inhaled corticosteroids.

Limitations
This data represents a specific patient population enrolled in a telemedicine program at a single center and may not be generalizable to other populations. As mentioned above, past medical history data is missing for approximately 30% of the cohort due to changes in data collection methods during the period reviewed. Thus, the population studied may differ in chronic condition status from the general population. Additionally, ICS and oral steroid regimens were not standardized. Although ICS and oral regimens pre-COVID-19 were not standardized for acute and sub-acute viral illness, variability in medications and dosing could affect the outcome.

Conclusion
Our review did not reveal a difference in the long-term outcomes from COVID-19 when oral steroids are prescribed as compared to ICS. Thus, the prescribing of ICS or oral steroids should not be avoided. Although there are myriad reasons to choose one delivery route over another, including cost, side effects, ease of use, and patient preference, our results add to the body of knowledge that steroids remain a potent treatment for the out-patient with acute and post-acute COVID-19.