Study Shows That Long COVID Probably Caused By SARS-CoV-2 Induced Sustained Biochemical Dysregulation Including Elevated Dimer And Ferritin
Long COVID News
: A new study led by researchers from Columbia University-USA along with support of scientists from the Zan Mitrev Clinic-North Macedonia and University of Florence-Italy has found that Long-COVID is associated with sustained biochemical disturbances especially elevated levels of D-dimers and Ferritin.
The Study team aimed to evaluate the incidence of Post-Acute Sequelae of COVID-19 or PASC (Long COVID) in previously hospitalized COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity.
A total of
168 COVID-19 patients previously hospitalized at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. The study team assessed the incidence of PASC and compared the biochemical profile.
The median hospitalization and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy “non-COVID-19” control cohort, the team observed that severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively.
The study findings found that
previously hospitalized severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.09.02.21262599v1
Many past studies have repeatedly demonstrated that a large percentage of individuals with a prior SARS-CoV-2 infection exhibit lingering symptoms such as fatigue, dyspnoea, and impaired pulmonary function, particularly amongst those with a history of severe COVID-19.
The biochemical parameters of long-COVID patients with prior mild, moderate, or severe COVID-19 that resulted in hospitalization were tracked in detail n this study, finding a characteristically dysregulated immune and inflammatory response in the most seriously ill.
The study involved a total of 168 COVID-19 patients that had been hospitalized for at least three days and had robust laboratory data available were recruited for the study. All donated further blood specimens for testing on average two months later.
The study findings showed that 56.5% of all participants reported long-COVID symptoms at the time of second sampling, and as the participants were categorized based on disease severity at the time of admission and during their stay at hospital the group note that 63.54% of those with long-COVID had previously been diagnosed with severe COVID-19, compared with around 20% each of those classed as mild or moderate, respectively.
It was found that 60.4% of those that
had previously suffered from severe COVID-19 developed long-COVID, while 47.4% and 58.6% of patients with mild or moderate COVID-19 developed long-COVID, respectively, according to clinical assessment of symptoms.
However unlike other studies or Long COVID News
, this finding suggests that there is no significant correlation between disease severity and the probability of developing lingering symptoms. Those with prior severe illness made up a more significant proportion of those with long-COVID in the sample.
It should be noted however that the participants in this study were each hospitalized for at least three days, and thus results are likely to be skewed towards individuals more likely to experience poorer health.
Detailed biochemical testing of severe COVID-19 patients now with long-COVID demonstrated upregulated ferritin, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), and interleukin(IL)-6 levels at later time points, with the most severe cases also displaying dysregulated white blood cell profiles.
It was also found that in those with mild to moderate COVID-19 only D-dimer levels were slightly elevated, with all other tested parameters returning to baseline by the second sampling.
Importantly more elevated levels of D-dimer and ferritin were observed amongst the severely ill at hospital admission and at later time points, as has been reported in other studies, with ferritin, in particular, exhibiting extremely high levels, in particular, the severely ill.
The study team speculates that this may be due to unbound iron playing a role in inflammation. They also suggest that sustained LDH levels in the severely ill may be an indication of ongoing lung repair.
Also the elevated inflammatory agents such as CRP and IL-6 may result from greater levels of lung damage and hypoxia experienced during illness.
Many other past studies have also reported ongoing elevated levels of IL-6 with the presence of pulmonary lesions in those recovering from severe COVID-19, which the study team suggests coincides with the reported greater incidence of long-COVID symptoms in this group.
Among the most commonly reported symptoms from the severe group with long-COVID was lung or chest pain, which is reported around half as often by those with prior mild or moderate COVID-19, with fatigue being most commonly reported in 16%, 20%, and 24% of mild, moderate, or severe patients, respectively.
Importantly individuals that experienced only mild or moderate COVID-19 and were considered to have long-COVID based on symptoms appear to have been overrepresented in this study, with almost 60% of individuals in any category of severity reportedly experiencing lingering symptoms for as long as three months post-hospitalization.
It must be also noted that although the biochemical profile of those with either mild or severe COVID-19 differed substantially during hospitalization and follow-up, those with a history of severe COVID-19 could be differentiated from the mildly or moderately ill by their significantly dysregulated biochemical profile.
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