#17,501
Although many people sill discount the risks, there is growing evidence that SARS-CoV-2 infection can lead to persistent - and sometimes permanent - sequelae, what is commonly called `Long COVID', Post-COVID Syndrome, or sometimes post-acute sequelae of COVID-19 (PASC).It doesn't happen to everyone, but estimates range (based on varying criteria) that anywhere between 10% and 50% of COVID survivors will experience some degree of lingering after-effects.
While most eventually recover, for some this post-COVID sequelae can be both debilitating, and permanent. There is also growing evidence that repeated infections with COVID increase the risks of Long COVID, disability, and death (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection).
Study: SARS-CoV-2 Infection and Viral Fusogens Cause Neuronal and Glial Fusion that Compromises Neuronal Activity
JAMA: Additional Evidence Of A Post-COVID/Diabetes Link
EID Journal: Postacute Sequelae of SARS-CoV-2 in University Setting
Nature: Long-term Cardiovascular Outcomes of COVID-19
The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 Infection
MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents
To this growing list of studies we have a preprint from the Netherlands's RECoVERED Study Group from the Public Health Service of Amsterdam and Amsterdam UMC, which finds links between long COVID and elevated inflammatory profiles (cytokines) following COVID illness.
While they say immune dysregulation does not completely explain Long COVID, it appears to play an important role, and elevated Interleukin-1 beta levels were strongly predictive of ongoing PASC at 6 months.
Due to its length and technical nature I've only reproduced the abstract and few excerpts below. Follow the link to read the report in its entirety.
Inflammatory profiles are associated with long COVID up to 6 months after illness onset: a prospective cohort study of individuals with mild to critical COVID-19
Elke Wynberg, Alvin X. Han, Hugo D.G. van Willigen, Anouk Verveen, Lisa van Pul, Irma Maurer, Ester M. van Leeuwen, Joost G. van den Aardweg, Menno D. de Jong, Pythia Nieuwkerk, Maria Prins, Neeltje A. Kootstra, Godelieve J. de Bree the RECoVERED Study Group
doi: https://doi.org/10.1101/2023.06.14.23291395
Abstract
Background After initial COVID-19 disease, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC.
Methods RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after illness onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects.
Results 186/349 (53%) participants had ≥2 serum samples and were included. Of these, 101 (54%: 45/101[45%] female, median age 55 years [IQR=45-64]) reported PASC at 12 and 24 weeks after illness onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR=40-56]). PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks in the multivariate model. Early (0-4 week) IL-1β and BMI at illness onset were predictive of PASC at 24 weeks.
Conclusions Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among those individuals with reduced pulmonary function. Early IL-1β shows promise as predictors of PASC.
COVID-19 is associated with persistent elevation of pro-inflammatory cytokines
First, we determined how the levels of cytokines in the study participants with SARS-CoV-2 infection compared to the uninfected reference group. Within the first 4 weeks after symptom onset, levels of IP10, IL10, IL17, IL1β, IL6 and TNFα were significantly elevated among participants infected with SARS-CoV-2 compared to reference samples (Supplementary Figure S1; Supplementary Table S2). Levels of IL10, IL17, IL1β and IL6 also remained elevated up to 21-24 weeks after SARS-CoV-2 infection in study participants as compared to the reference group (Supplementary Figure S1). Cytokine correlation matrices are shown in Supplementary Figure S2. These data indicate the presence of immune dysregulation in study participants with COVID-19.
(SNIP)
Conclusions
In summary, our study indicates that immune dysregulation does not single-handedly explain PASC as defined by self-reported symptoms. However, confirmation of PASC status with impaired pulmonary function as an objective measure revealed an association with raised pro-inflammatory cytokines, as previously reported in other studies. In addition, early raised IL1β levels were strongly predictive of ongoing PASC at 6 months in our analyses. Our findings therefore suggest that immune dysregulation plays an important role in the pathogenesis of ongoing symptoms in some individuals.
There is little doubt that Post-COVID syndrome is real, and for an as-yet unquantified percentage of the population, it can prove severe enough to cause permanent disability and even premature death.
The $64 question is how big of a problem this is going to become.
Some experts have suggested we may see huge increases in COVID-19 related heart failure and neurological diseases in the years ahead.
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575
Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms
Emily A. Troyer, Jordan N. Kohn, and Suzi Hong
The truth is, we don't know, and may not know for another 5 or 10 years.
