Abstract Background: Post-COVID-19 cognitive impairment (PCCI), characterized by deficitsin attention, memory, and executive functioning, remains a major challenge among patientswith long COVID. Oxidative stress is a key contributor to this condition. Cysteine-richwhey protein isolate (CRWPI), such as Immunocal®, enhances intracellular glutathioneproduction and may offer neuroprotective benefits.Objective: To evaluate the efficacy of Immunocal® supplementation on cognitive function,particularly attention and memory, and functional performance in individuals with ICCP.Methods: A randomized, controlled, parallel-group trial was conducted in Cali, Colombia,with 120 adults recovering from COVID-19 with mild to moderate cognitive impairment.Participants were randomly assigned to three groups: (1) immune® supplementation (CRWPI)(20 g/day), (2) neuropsychological rehabilitation, or (3) no intervention (control), for12 weeks. Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA)and the NEUROPSI attention and memory test. Physical endurance was measured using the30-second foot test (STST). Clinical symptoms evaluated through a medical assessmentform, before and after the intervention, were also taken into account. Results: Both theImmunocal® and neurorehabilitation groups showed statistically significant improvementsin all attention subdomains and memory types compared to the control. Immunocal® producedgreater gains in divided attention and working memory, suggesting a specific advantage incognitive domains sensitive to oxidative stress. STST performance was also significantlyimproved in the Immunocal® group. No significant improvements were seen in the controlgroup.Conclusion: Immunocal® supplementation significantly improves cognitive performance,comparable to structured neurorehabilitation, in individuals with ICCP. It also showspotential to improve physical endurance, clinical symptoms, and reduce fatigue. Thesefindings support the integration of Immunocal® as a non-pharmacological intervention forcognitive dysfunction related to long COVID.
Study Design and Participants This randomized, controlled, parallel-group trial included
subjects at least 18 years of age in Cali, Colombia, who recovered from COVID-19
infection and presented with mild to moderate cognitive impairment and no history of
Immunocal administration. Subjects with a history of cerebrovascular or cardiovascular
disease and current or previous use of Immunocal were excluded from screening. Ethical
approval was obtained from the IRB of the Universidad Libre and informed consent was
obtained.
Sampling and protocol A consecutive non-probabilistic sampling was performed. For this
study, a target sample of 120 subjects was selected to achieve a 95% confidence level. A
double-blind randomization process was used to divide subjects into three groups of 40
participants as follows: 1. CRWPI (Immunocal®) supplementation; 2. Structured
neuropsychological rehabilitation (Neurorehabilitation), and no intervention (control).
A group of neuropsychologists with experience in the application of cognitive tools and
neuropsychological rehabilitation were responsible for the evaluation and management of
the neuropsychological phase of the study. Neuropsychological rehabilitation consisted of
45-minute face-to-face group sessions that were conducted three times a week over a
12-week period. After 12 weeks, a neuropsychological evaluation was completed on each
subject.
CRWPI Immunocal® (Immunotec ™) was administered at a dose of 20 grams (2 sachets once
daily) for 12 consecutive weeks. The research team delivered the Immunocal directly to
the subjects and instructed them how to mix and self-administer it.
Pre-test cognitive functioning was assessed using NEUROPSI attention and memory, while
only NEUROPSI attention and memory were used to assess the same cognitive domains at 12
weeks.
The main objective of NEUROPSI Attention and Memory is to assess a broad spectrum of
cognitive functions, including spatial, temporal and personal orientation; attention and
concentration; working memory; verbal and visual memory, and executive and motor
functions. The NEUROPSI Attention and Memory test considers age and schooling for the
acquisition of quantitative and qualitative data and classifies amnesic and attentional
alterations into four different categories.
The 30-second sit-stand (STST) test is a widely used assessment designed to assess
lower-body strength and functional endurance.19 It measures how many complete stops a
person can complete from a seated position in 30 seconds, without using their arms for
support. This test provides valuable information about muscle strength and balance,
making it a practical tool for monitoring physical performance and the effectiveness of
interventions such as exercise programs or nutritional supplements. STST is often used to
assess fatigue in the muscles of the lower extremities and trunk. This test was performed
on all available participants after the intervention period was completed.
The participants were also evaluated before and after the intervention by the doctors of
the research group, through a medical assessment form where all clinical symptoms due to
the virus were recorded.
Other: Intervention with Consolidated Cysteine (Immunocal) 20 g per day
CRWPI Immunocal® (Immunotec™) was administered at a dose of 20 grams (2 sachets once
daily) for 12 consecutive weeks. The research team delivered Immunocal directly to the
subjects and instructed them on how to mix and self-administer it.
Behavioral: Cognitive rehabilitation workshops
Neuropsychological rehabilitation consisted of in-person group sessions for 40 adults (18
years or older) to work on cognitive functions such as memory and attention. Each session
lasted 45 minutes. These sessions were held three times a week for a period of 12 weeks.
Inclusion:
- Adults ≥18 years with confirmed prior COVID-19
- with persistent cognitive symptoms
- able to complete testing
- and willing to consent.
Exclusion:
- Pre-existing dementia or major psychiatric illness
- whey protein allergy - participation in another cognitive trial
- severe hepatic/renal/metabolic disease, pregnancy
- or any condition interfering with participation.
Doctor's office
Cali 3687925, Valle del Cauca Department 3666313, Colombia
Ingrid Mena, Neuropsychologist, Principal Investigator
Universidad Libre