Long COVID following Mild SARS-CoV-2 Infection: Characteristic T Cell Alterations and Response to Antihistamines

Abstract

Long COVID is characterized by the emergence of multiple debilitating symptoms following SARS-CoV-2 infection. Its etiology is unclear and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRAs) suggest a histamine-dependent mechanism that is distinct from anaphylaxis, possibly mediated by T cells, which are also regulated by histamine. T cell perturbations have been previously reported in post-viral syndromes, but the T cell landscape in patients who have recovered from mild COVID-19 and its relationship to both long COVID symptoms and any symptomatic response to HRA remain underexplored. We addressed these questions in an observational study of 65 individuals who had recovered from mild COVID-19. Participants were surveyed between 87 and 408 days after the onset of acute symptoms; none had required hospitalization, 16 had recovered uneventfully, and 49 had developed long COVID. Symptoms were quantified using a structured questionnaire and T cell subsets enumerated in a standard diagnostic assay. Patients with long-COVID had reduced CD4+ and CD8+ effector memory (EM) cell numbers and increased PD-1 (programmed cell death protein 1) expression on central memory (CM) cells, whereas the asymptomatic participants had reduced CD8+ EM cells only and increased CD28 expression on CM cells. 72% of patients with long COVID who received HRA reported clinical improvement, although T cell profiling did not clearly distinguish those who responded to HRA. This study demonstrates that T cell perturbations persist for several months after mild COVID-19 and are associated with long COVID symptoms.

Rare Skin Reactions after mRNA Vaccination, Similar to Jones–Mote Basophil Responses

“…An example may be the improvement that was seen in patients with long Covid who were treated with combined antihistamines, since the source of histamine may be the basophils. 5 …”

Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells

“…Exploration of protein-protein interactions (PPI) to detect possible modules among these 38 DMGs revealed that most of the proteins were connected in a expression of ACE2 in neurons and SARS-CoV-2 binds to the ACE2 receptor via the S (spike) protein to enter cells. Histamines have been demonstrated to play a role in PACS, as partial symptom relief was reported in PACS patients upon treatment with antihistamines [7]. The pathways regulated by muscarinic receptors CHRM1&3 play a role in odour perception and were found to be epigenetically modulated in patients with PACS.…”

Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms

“…Based on these results, it is likely that vaccine induction of CD8+ T cells to more conserved antigens such as the nucleocapsid, rather than just to SARS-CoV-2 spike antigens, may add benefit to more rapid containment of infection [ 21 ]. Patients with long COVID had reduced CD4+ and CD8+ effector memory (EM) cell numbers; this T cell perturbations persisted for several months after mild COVID-19 and was associated with long COVID symptoms [ 22 ]. Seeing the importance of the CD8+ cells against nucleocapsid in an adequate immune response against SARS-CoV-2, it is hypothesized that the inadequacy of humoral immunity, i.e., the low titer of antibodies against nucleocapsid, also draws attention to the inadequate immune response and consequently may be a cause of persistent symptoms after COVID-19.…”