Observational Study
J Investig Med 2022 Jan;70(1):61-67.
doi: 10.1136/jim-2021-002051.Epub 2021 Oct 5.
Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines
Non randomised and non blinded. 49 patients were recruited and received standard care. They completed a symptom questionnaire and blood was tested.
The average symptom duration was 268.9 days (range 87 - 402 days) at the time of referral and participation.
The paper is contradictory. At one point it states that all patients were offered HRAs but it later says not all were offered because some patients were first seen before HRAs became part of treatment.
26 patients consented to take a combination of H1 and H2 histamine receptor antagonists (HRAs) for a minimum of 4 weeks and they completed initial and follow up assessment questionnaires. The mean time to response was 29.6 days (median
26 days; range 6–89 days).
The 23 patients who did not receive HRAs were also reassessed between 28 and 119 days after their initial blood tests (median
56 days).
Does this mean that the untreated group were assessed twice (at referral and follow up ) but that the treated group were assessed three times (referral, start of treatment and follow up)? It's hard to be sure but the untreated group had a longer period during which to show improvement.
Whatever the actual timing, the treated and untreated groups together reported more symptoms at referral and participation than they did at initial assessment so symptoms were already improving before treatment was offered.
The average symptom burden per patient +/- SD in the treatment group was 4.28 +/- 1.70 at initial assessment and 2.68 +/- 1.97 at follow up. In the untreated group it was 4.91 +/- 2.57 and 4.39 +/-2.49.
In the treatment group, symptoms in all categories improved except dysautonomia and in some categories there was a clear reduction. See Table 2 in the paper. (Dysautonomia was rather narrowly defined as postural tachycardia syndrome.)
What to make of it?
The duration of illness at referral was between 3 and 13 months. I've been away a while but if the Dubbo study is still considered the standard, then it would be nice to have confidence that illness duration was matched in the treated and untreated groups. A significant proportion of patients particularly at the lower end of the time period would be expected to improve spontaneously.
The treatment was not blinded but at face value, the improvement in some of the symptom categories was impressive, particularly for fatigue, chest pain and neurologic, which included brain fog and headaches.
The authors noted that
All symptoms improved except dysautonomia, suggesting that this arises through another mechanism. Indeed, dysautonomia following other viral infections is associated with autoantibodies to adrenergic and cholinergic receptors, is linked with autoimmune phenomena.
I would like to be more excited about this than I am because orthostatic intolerance (probably not PoTS) was a symptom of mine that took a long time to improve but 4 of 26 is far too small a number to be drawing any conclusions about.
That dysautonomia category is generally bothersome. The orthostatic intolerance and autonomic dysfunction category from the ME/CFS NICE guidelines would have been an improvement but unfortunately they were published after this study was run. I can't help thinking it would have caught more than 4 of 26 patients. A pity.