Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in pw Post-COVID (...), 2021, Molnar et al

[Wyva]

Full title: Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms

Abstract

Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies.

Methods: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4–12 weeks after onset of symptoms, and beyond 12 weeks.

Results: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4–12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4–12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (−0.359, p < 0.001).

Conclusion: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.

Open access: https://www.mdpi.com/2077-0383/10/19/4337

 

[Wyva]

This is a Hungarian study and they also mentioned CFS later:

The exact cause of post-COVID fatigue is still unknown, but in many features it shows similarities to other chronic fatigue syndromes (CFSs) [32]. A study examining the relationship between immune function and CFS after infectious mononucleosis found that a subset of patients had undetectable Epstein–Barr nuclear antigen (EBNA) Ig titres and diminished immune response against EBV [33]. Our theoretical consideration is that chronic fatigue may be caused by chronic inflammation, and the lower level of antibodies in patients with severe fatigue indicate an unsatisfactory immune response against the viral pathogen.

Based on analogy with other similar syndromes, there are several possible mechanisms that might explain this theory. Presumably, the immune system of some patients is poorly activated, resulting in a decreased production of immunoglobulins, slower viral clearance from infected cells, and thus the maintenance of a prolonged inflammatory state which manifests in chronic fatigue. This can be seen after Q fever, where elevated levels of IFN-gamma, IL-1 and IL-6 may underlie chronic fatigue. Q fever fatigue syndrome (QFS) patients show signs of altered immunity and inflammatory profile compared to asymptomatic Q fever seropositive controls [34].

The expression of mitochondrial-derived peptide (MDP)-coding genes MT-RNR1 (MOTS-c) and MT-RNR2 (humanin) are decreased in CFS, QFS and to a lesser extent in Q fever seropositive controls, resulting in a decreased production of humanin. These peptides might be important in the pathophysiology of both QFS and CFS [35,36]. Another mechanism which could contribute to the alterations in antibody response against COVID-19 is that the different spike or nucleocapsid variations affect the immune mechanism in a similar way to EBV infection regarding the EBNA variations [33].

A further possibility is that COVID-19-associated changes in the intestinal microbiome could be a possible consequence. In case of Q fever, it has been shown that the Bacteroidetes and Firmicutes abundance are reduced in chronic fatigue syndrome compared to healthy individuals [37]. In COVID-19, an increase in Collinsella spp. has been observed. This bacterium has an important role in the maintenance of chronic inflammation [38]. Given the paucity of evidence available, further studies are needed to clarify the exact mechanism of fatigue after COVID-19 infection.