Researchers from the North Bristol NHS Trust, Academic Respiratory Unit in Bristol, UK, recently uploaded study results to the medRxiv preprint server.  The study team sought to identify if the corticosteroid dexamethasone, proven to reduce COVID-19 mortality in certain hospitalized acute COVID-19 pneumonia scenarios thanks to the RECOVERY trial, could help reduce symptoms associated with long-COVID.

The RECOVERY trial led to a material change in how acute COVD-19 was managed, and according to the study authors, saved approximately 1 million lives worldwide

Importantly, however, steroids have a downside, even if administered on a short-term basis. In the case of the RECOVERY trial, the benefits were constrained to patients requiring oxygen or already on a ventilator as compared to patients less severely affected—the latter could actually be harmed by the regimen. 

A Real Problem

Long-COVID, also known as post-COVID-19 syndrome, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CSS) is characterized by long-term sequelae appearing or persisting well after the preliminary infection period associated with SARS-CoV-2. This condition may impact every organ system with sequelae, including respiratory disorders, nervous system and neurocognitive disorders, mental health issues, metabolic disorders, and more.Subscribe to the Trialsitenews “COVID-19” ChannelNo spam – we promise

A recent study covered by TrialSite suggests vaccination doesn’t help stave this condition off if the individual experiences a breakthrough infection. Presently, there are no treatments. The total number of COVID-19 patients that end up experiencing long COVID ranges from a range of 10% to 30%. However, one study led by the University of Oxford revealed about 37% of 273,618 COVID survivors experience the condition.

It turns out that many survivors of acute COVID-19 are afflicted by long COVID.

The Study

Conducted at UK hospitals, the study team was able to enroll 198 patients who happened to be admitted with COVID-19 pneumonia all from one UK hospital during the period of April 2020 to August 2020. The study authors sought to answer what is the quality of life of those people eight months after COVID-19 hospitalization. Would the use of the corticosteroid reduce or mitigate long COVID symptoms? 

Participants were tested positive during polymerase chain reaction (PCR) testing for SARS-CoV-2, or a clinical-radiological test for the novel coronavirus. The exclusion criteria applied to any patients who were either A) already receiving dexamethasone a couple of weeks prior to admission or B) any subjects needing a long-term steroid prescription.

The study subjects, segmented into two cohorts, received six milligrams (mg) of oral dexamethasone one time daily in addition to a control group. The study investigators ensured that both cohorts were balanced in terms of demographics (e.g., age, gender, etc.), in addition to other attributes such as comorbidities and need for ventilation.  The authors note that they included more marks in the control group. 

The Results

For those COVID-19 survivors that endured acute pneumonia, a striking 68% were disclosed to have at least one ongoing problematic symptom eight months after the initial SARS-CoV-2 condition. The study team analyzed results based on the symptoms reported below.

Symptoms at 8-month follow-up comparing dexamethasone group (orange) to no dexamethasone group (green).

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The UK-based authors note:

There are several hypotheses on the pathophysiology of Long Covid including the persistence of the virus, development of auto-immune disease, or a product of organ damage during the acute phase. All might be theoretically affected by steroid use in either a positive or negative direction. Reassuringly, this case-control study suggests that dexamethasone given in the acute phase of COVID-19 is associated with reduced long-term symptoms.”

Reasons for this Observation?

The authors delineate a series of possible explanations for this observation including:

∙       Confounding by indication (those who receive steroids face a greater probability to recover regardless of the steroid prescription

∙       Reduced symptomatology may be associated with general improvements in care occurring during the pandemic leading to lower levels of long-term symptoms—but the counterargument here is that there is little evidence to support a reduction in long term symptoms of SARS-CoV-2 infection during the pandemic

∙       Those patients with more severe disease passed away and thus, were not available for follow up

∙       This just may be a causal association

Limitations

There are a number of limitations associated with this study. TrialSite notes the results are not yet peer-reviewed and thus, it’s not a good practice to cite as evidence. 

∙       Small sample size

∙       Analysis limited to patients who needed oxygen during the inpatient stay and therefore materially compromised

∙       The authors remind that in RECOVERY dexamethasone “shows a trend toward harm in hospitalized patients not requiring oxygen” thus this analysis should not be a basis to over-prescribe dexamethasone. 

Conclusion

This case-control study demonstrates that study patients who received oral dexamethasone while hospitalized due to their SARS-CoV-2 infection were less likely to experience persistent symptoms at month 8 of a follow-up.

About North Bristol NHS Trust

Part of the British public health system, this health system employs over 8,000 staff delivering healthcare across Southmead Hospital Bristol, Crossham Hospital, and the Bristol Centre for Enablement. The health system provides community healthcare and hospital services to Bristol, South Gloucestershire, and North Somerset, England. The facility includes an academic medical center as well as clinical trials.

Lead Research/Investigator

∙       Alice Milne, North Bristol NHS Trust, Academic Respiratory Unit

∙       S. Maskell, North Bristol NHS Trust, Academic Respiratory Unit

∙       Fergus Hamilton, North Bristol NHS Trust, Academic Respiratory Unit

∙       David Arnold, North Bristol NHS Trust, Academic Respiratory Unit

∙       C Sharp, Gloucester Royal Hospital

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