Today I am going to review a recent paper by Spanish research scientists Utrero-Rico et al entitled "A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID". It, I think, endorses Dr Bruce Patterson's research as Incelldx in the use of steroid medication for those with Long Covid and, because steroids are used in the treatment of many autoimmune disorders, is topical with the announcement of the placement of Long Covid on the Autoimmune Registry.
Why did they do it?
Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterised, and there is no established therapy. This research team aimed to investigate the existence of immune alterations that might underlie long-COVID.
What did they do?
They performed a deep immune profiling in nine patients with persistent symptoms, before and after a 4-day steroid course. Eight out of nine patients were female with a median age of 42 (range from 30 to 61). They described the following symptoms:
Arthralgia (78%) - joint pain
Myalgia (89%) - muscle pain
Dyspnea (89%) - shortness of breath
Asthenia (89%) - physical weakness, lacking in energy
Paresthesia (78%) - numbness, tingling, pricking, burning, chilling sensations
Anxiety (56%) - or I wonder hyperadrenergic POTS?
Cognitive dysfunction (44%)
Anosmia (33%) - loss of smell
Dysgeusia (22%) - altered taste
They also did this with five post-COVID-19 patients without persistent symptoms.
The steroid was Prednisolone and it was given at a strength of 30 mg per day for 4 days.
What did they find?
Figure 1 - Study design included three groups of post-COVID-19 patients: five subjects who recovered completely (green) and nine subjects with persistent symptoms (orange), eight of whom were sampled again after 4 days of prednisone treatment (blue).
The persistent symptom group (PSP) and the non persistent group (NSP) are distanced from each other in 'b" . While the group who had 4 days of prednisolone (TTP) occupied an intermediate position and showed more similarity with NSP than with themselves before treatment.
"These results suggested that symptomatic patients present immune alterations that are corrected to levels similar to asymptomatic patients after corticosteroid treatment"
Also they found:
1. Those with persisting symptoms showed an uneven distribution of certain circulating mononuclear cell populations - this reflects IncellDx findings.
2. Symptoms in the persistent symptom group were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker.
3. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration.
What are the limitations of the study?
The present study has several limitations.
The small number of patients in each cohort
The selection of patients who reported particularly severe myalgia and/or arthralgia (which are the symptoms that steroids are typically used for so may be biased selection) together with other symptoms
The duration of the clinical improvement beyond 4 months post-treatment was not investigated,
These limit the conclusions of the study and do not allow the characterization of different long-COVID phenotypes and whether a longer corticosteroid treatment could be more appropriate is still unclear.
What did they conclude?
They provided evidence that the persistent symptoms of long-COVID may be accompanied by immunological alterations characterised by inflammation and reduced immune regulation. These alterations were observed over a year after acute infection. A short course of corticosteroids reverted these immune alterations and led to clinical improvement of persistent symptoms, both of which were maintained 4 months after treatment.
The current study highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.
image - @_coronadiary