Persistent Inflammation and Post-COVID Syndrome
By Joseph John, MD, FIDSA, FSHEA
Clinical Professor of Medicine and Microbiology, Medical University of South Carolina and Lowcountry Infectious Diseases, Charleston
SYNOPSIS: Ongoing inflammation may contribute to long COVID.
SOURCES: Acosta-Ampudia Y, Monsalve DM, Rojas M, et al. Persistent autoimmune activation and proinflammatory state in post-coronavirus disease 2019 syndrome. J Infect Dis 2022; Jan 25. doi: 10.1093/infdis/jiac017. [Online ahead of print].
Heesakkers H, van der Hoeven JG, Corsten S, et al. Clinical outcomes among patients with 1-year survival following intensive care unit treatment for COVID-19. JAMA 2022;327:559-565.
The emergence of a complex syndrome following infection with COVID-19 has been termed long COVID or long hauler illness. Among the approaches to understanding this syndrome have been immunological studies, with several recently concentrating on T-cell abnormalities that may be associated with autoimmune reactivity and long-term symptoms.
Acosta-Ampudia et al analyzed 12 of 33 patients with post-COVID syndrome (PCS) for cytokine changes and lymphocyte populations over a seven- to 11-month period. Autoimmune profile and immunological statuses showed that latent autoimmunity and overt autoimmunity persisted over time. A pro-inflammatory state showed increased interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1β, and IL-13, while interferon-γ-induced protein 10 (IP-10) was decreased. Additionally, other cytokine increases in PCS showed increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells.
The extent of the problem of PCS in patients who had required intensive care for the acute infection has been elucidated by Heesakkers and colleagues in the Netherlands. They recruited cases from 11 Dutch hospitals participating in the MONITOR-IC study of survival and costs in intensive care unit (ICU) patients. Cases in this study were survivors with a discharge diagnosis of confirmed COVID-19 and were followed for one year.
Of 452 patients eligible for entry into the study, 246 completed the one-year analysis. The mean age was 61 years, and 71.5% were men. These patients were all treated for COVID-19 in the ICU and at one year. Overall, 56% considered themselves to be fatigued, and 66% thought they had physical problems, notably a weakened condition (39%), joint stiffness (26%), joint pain (25%), muscle weakness (25%), myalgia (21%) and dyspnea (21%). Mental problems included anxiety or depression (18%) and post-traumatic stress disorder (10%). The cognitive test score median was 25 (interquartile range [IQR], 12-37), and 16% reported cognitive symptoms. In addition to the aforementioned symptoms reported, there were 20 other symptoms reported, including loss of taste or smell (15% to 17%), tingling of a limb (20%), dizziness (11%), hair loss (7%), and headache (5%).
COMMENTARY
The paper by Heesakkers et al reports rates of many symptoms that are higher than in previously published post-COVID-19 studies, although most of the comparative studies did not have follow-up periods as long as one year. On the other hand, when compared to non-COVID-19 patients in the MONITOR-C study, the incidences of lasting physical, mental, and cognitive symptoms were similar. Clearly, the overall physical, mental, and cognitive long-term symptoms of the non-COVID-19 vs. a COVID-19 group are not markedly different. The rates of more specific symptoms, such as tingling of a limb, hair loss, and joint and muscle symptoms, however, seem much higher than those of non-COVID patients.
Fatigue may be the most bothersome PCS symptom. In my experience taking care of many patients with chronic fatigue syndrome, the quality of post-COVID-19 fatigue is quite similar, with elements of pure exhaustion and post-exercise malaise. This current study clearly gives us some objective measurement we can use for comparison in future studies.
As with chronic fatigue syndrome, the patho-physiology of PCS remains unknown. The apparent persistent pro-inflammatory state identified by Acosta-Ampudia has been suggested as one possibility for both. The authors concluded that long-term persistent immune activation may contribute to the development of latent or overt autoimmunity.
My hope is that the type of monoclonal therapy we have seen for direct antiviral targeting of COVID-19 will become helpful for the autoimmune dysregulation prevalent in PCS.
Ongoing inflammation may contribute to long COVID.
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