So-called alternative medicine for long COVID: a systematic review of randomized controlled trials

So-called alternative medicine (SCAM) interventions are often being discussed as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. This review aims to review existing published studies on the use of SCAM interventions for patients experiencing long COVID through a systematic review.

A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of SCAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.

A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that SCAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

The authors concluded that SCAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on SCAM for long COVID are warranted in the future.

The review’s aim is, in my view, nonsense. SCAM is a diverse field which means that the review must capture a wide range of therapies each represented by just one or two primary studies. In turn, this means that general conclusions across all SCAM will be highly questionable, if not misleading.

Furthermore, I find these conclusions odd and irresponsibly misleading. My main reason for this is the poor methodological quality of the primary studies:

• Four trials were considered to have unknown bias risk for generating the random sequence due to insufficient information about the specific method of randomization used.
• Only 5 of the trials provided appropriate random allocation concealment.
• Only 5 trials were blinded to both participants and personnel.
•  Three trials were rated as unknown risk of bias since insufficient information was provided.¹
• Four trials failed to performed outcome assessment blinding.
• One trial did not report detailed information about drop-out cases and was defined as high risk of bias. 
• Three study protocols were unavailable and had relevant outcomes that were not reported in the pre-specified way.

Moreover, safety cannot possibly be reliably estimated on the basis of the data. And finally, the statement that SCAM interventions may be effective, as the authors put it, is in my view not a valid conclusion but a silly platitude.

I therefore suggest to re-formulate the conclusion of this review as follows:

At present there is no sound evidence to assume that any SCAM intervention is effective in the management of long COVID.