1. What data in particular will be shared?
   Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
   


2. What additional supporting information will be shared?
   Response - None of the above
   
   
3. Who will be able to view these files?
   Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
   


4. For what types of analyses will this data be available?
   Response - For individual participant data meta-analysis.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [drguru1990@gmail.com].
   


6. For how long will this data be available start date provided 01-09-2022 and end date provided 31-08-2025?
   Response - Beginning 9 months and ending 36 months following article publication.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - nil

Coronavirus disease-19 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide pandemic afflicting a large population. Most infected people develop acute symptoms that last for 7–10 days. However, one or more symptoms (physical, cognitive and/or psychological) persist for weeks or even months in a substantial percentage of people [1]. Fatigue is the most persistent and debilitating symptom of long COVID [2]. Studies revealed that 52% of the subjects among the studied population showed fatigue/myalgia post-COVID-19 [3,4]. A survey done by the Office for National Statistics (ONS) in the United Kingdom suggests that about one in five people have symptoms of long COVID five weeks after an initial infection and one in ten after twelve weeks [5]. The chronic phase of COVID-19 is speculated to be perpetual, with impaired functional status and quality of life [6].

Though the data on COVID fatigue is still emerging, viral infections are known to trigger chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), in patients. There are no specific biomarkers, and diagnosis is typically based on symptoms. In fact, a subset of patients suffering from COVID-19 satisfied the diagnostic criteria of CFS/ME [7] In addition, major post-acute COVID-19 symptoms resemble post-infectious ME/CFS [8]. The changes in neurotransmitter levels, inflammation, psychological disorders, stress levels, and cognitive dysfunction are thought to be contributing factors in fatigue [2]. An increase in the level of pro-inflammatory cytokines and overexpression of interleukin 6 (IL-6) are associated with persistent inflammation and fatigue [9]. Further, immune dysregulation and mitochondrial dysfunction are common causes of fatigue after viral infection [10].

Thus, management approaches that address these varied patho-physiologies can be evaluated for post COVID fatigue. While the majority of current treatments for fatigue are palliative, including rehabilitation through spa facilities with multidisciplinary interventions, and are restricted to alleviating symptoms [11], there are indications that certain supplements may be useful in addressing factors potentially involved in the pathogenesis of fatigue. Probiotics have been evaluated in the management of CFS. A significant decrease in anxiety symptoms and modifications in the well-being status, inflammatory and oxidative indexes in CFS patients were seen with probiotics supplementation [12,13]. Antioxidants and immunomodulators have also been explored to combat fatigue [14–16]. Aswagandha (Withania somnifera) have been a proven ayurvedic drug for treating fatigue [17]. Similar literature has also been found about other complementary medicines like Spilanthes acmella [16,18], Curcuma longa [19], Lactobacillus salivarius [20] and Saccharomyces boulardii [21]. A combination drug ProGenX (750 mg) comprising of the five above-mentioned herbs (Ashwagandha – standardised to 5% withanoloids (100 mg), Spilanthes acmella – standardised 3.5% spilanthol (300 mg), Curcuma longa – standardised to 95% curcuminoids (250 mg), Lactobacillus salivarius (50 mg), Saccharomyces boulardii (50 mg)) claims to be an effective formulation for combating fatigue. With this understanding, it is rational to examine the effect of ProGenX supplementation on COVID-19 induced fatigue.

Early assessments and intervention are critical in reducing COVID-19 induced fatigue, irrespective of initial illness severity [4]. Moreover, very limited interventional studies to reduce post-COVID fatigue have been published.