Relationship between immunological responses in the acute phase of SARS-CoV-2 infection and long-term cognitive deficits

By Tarun Sai LomteMar 8 2022Reviewed by Danielle Ellis, B.Sc.

A recent study posted to the Research Square* preprint server and under consideration at Scientific Reports reported that monocytosis during the acute phase of coronavirus disease 2019 (COVID-19) could forecast anosognosia in long COVID.

Background

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in respiratory symptoms to complex manifestations, including cognitive disorders. In some cases, the disease manifests into post-COVID-19 syndrome, aka long COVID, in which COVID-19-associated symptoms persist several months after recovery.

Persistent mental symptoms post-COVID-19 include memory deficits and impaired instrumental, executive, and attentional functioning that linger for several weeks to months after discharge/recovery. Individuals without prior neurological conditions could also manifest these impairments severely.

Initial reports suggest relatively heterogeneous neuropsychological profiles; anosognosia is one notable clinical feature in which self-awareness of neuropsychological deficits is impaired. Moreover, some patients present with extreme cognitive effects without any objective disorders, while others have no subjective complaints. Some others have found that anosognosia in patients with Alzheimer’s disease, multiple sclerosis, or human immunodeficiency virus (HIV) could predict the presence of neuropsychological symptoms and their intensity.

According to some studies, the severity of respiratory disorders during the acute phase of COVID-19 may not predict cognitive symptoms during long COVID. However, intrinsic risk factors like lifestyle, genetics and immunological profiles better predict the pathophysiological outcome of COVID-19 infection, ultimately resulting in cognitive impairment.

The study

The current study assessed whether immunological markers during the acute COVID-19 phase could forecast anosognosia. Specifically, the authors examined whether leucocyte profiles in patients exhibiting anosognosia during long COVID differed from those in the acute COVID-19 phase compared to those who do not develop anosognosia.

The researchers assessed 61 COVID-19 patients treated at Geneva University Hospitals (HUG) for six to nine months post-discharge. None of the participants had prior cognitive deficits. The immunological parameters were examined by collecting retrospective data from the hospital’s internal database. The inter-cohort analyses were carried out with the Mann Whitney U tests accounting for the nonparametric distribution of the two groups. Receiver operating characteristic (ROC) analysis was employed to identify the immunological variables that could forecast anosognosia during long COVID-19.

Results

The study comprised around 20 patients with anosognosia and 41 without. Of these, 38 patients had moderate COVID-19 with conventional hospitalization in the acute phase, while the remaining patients required intensive care unit (ICU) admission. No participant had a history of cancers, severe immunosuppression, or developmental disorders. Overall, the differences in sociodemographic and clinical variables exempting chronic renal failure were insignificant between the two cohorts.

The authors observed a higher percentage of monocytes in patients with anosognosia than non-anosognosia subjects. ROC curve analysis performed on 52 patients revealed that monocyte proportion during the acute phase was predictive of anosognosia after six to nine months of COVID-19. A Youden test was performed to ascertain the best cut-off and noted that the ROC curve analysis predicted 74.3% anosognosia cases six to nine months post-COVID-19 infection. It is noteworthy that neither basophil count nor C-reactive protein (CRP) levels could predict anosognosia or other associated cognitive disorders.

Conclusions

In summary, the authors noted a differential proportion of monocytes in the acute phase of SARS-CoV-2 infection between anosognosia and non-anosognosia patients. A mean percentage of monocytes in the blood circulation of about 7.35% or higher during the acute disease predicted anosognosia in the long-term with a sensitivity and specificity of about 80% each.

The current study suggested that anosognosia during long COVID might result from the immunologic imbalance during the acute infection phase. Furthermore, neutrophil count and neutrophil-to-monocyte ratio were lower in patients developing anosognosia than those who do not show anosognosia in post-COVID-19 syndrome. As both innate and adaptive immune responses are induced during SARS-CoV-2 infection, prospective anosognosia patients are likely to elicit innate monocyte/macrophage responses. In contrast, those who do not develop anosognosia have a predominant neutrophilic response.

Although CRP and basophil proportion were previously used to distinguish between patients requiring intermediate or ICU care, these parameters could not predict the prospective cognitive disorder(s) during long COVID. High abnormal levels of monocytes during acute COVID-19 were associated with increased disease severity, such as amplified inflammation and impaired production of type I interferons (IFN).

However, the present research established a link between monocytosis and anosognosia. Notably, this study is the first to correlate cognitive impairments with immunological variables in COVID-19, and the findings could help explore therapeutic interventions during acute disease to mitigate the effects of the prospective post-COVID-19 syndrome and associated neurocognitive syndrome.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources