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Procalcitonin levels predictive of severe disease in COVID-19

23rd July 2021

Measurement of procalcitonin levels was found to be most discriminatory for severe disease course among patients hospitalised with COVID-19.

Knowledge about COVID-19 has advanced at rapid pace over the last 15 months and with a large number of patients being admitted to hospital, it is of upmost importance to be able to assess which patients are at the highest risk of disease progression. Based on earlier observational studies, it has become clear that older patients and those with co-morbidities are more likely to develop severe disease and several biomarkers including C-reactive protein and procalcitonin, have been shown to be associated with severe disease. A further potential complication of COVID-19 is bacterial co-infection though in an analysis of 24 studies including 3338 patients, the presence of bacterial co-infection in COVID-19 was found to be very low at 6.9%. Nevertheless, whether the use of biomarkers such as procalcitonin could be used to identify bacterial co-infection among patients with COVID-19 has been suggested as a potentially valid strategy, but there is a lack of evidence to support this approach.

This absence of evidence prompted a team from the Department of Internal Medicine, Haga Teaching Hospital, Den Haag, The Netherlands, to retrospectively evaluate the association between multiple biomarkers, including procalcitonin and the clinical and microbiological outcomes in patients hospitalised with COVID-19. The team used data from the PredictED study, a single centre, prospective observational study, designed to evaluate procalcitonin as a marker for bacteraemia in patients who present to the emergency department. While the original study was designed to examine all patients admitted to the emergency department, the authors turned to a subset of patients with PCR-confirmed COVID-19. A number of tests were undertaken, including blood cultures, C-reactive protein and procalcitonin although the results of this latter test were not immediately available to the treating clinician. The primary outcome of the study was the incidence of bacterial co-infection at the initial emergency department presentation and its association with procalcitonin.

Findings
The subset of COVID-19 patients testing positive for the virus was 142 with a mean age of 61 years (66% male). More than half of these patients had co-morbidities including diabetes (25%) and cardiovascular disease (24%) and from the complete cohort, 41 developed severe COVID-19, all of whom were hospitalised and 24 (17%) subsequently died within 30 days. Procalcitonin levels were significantly associated with the development of severe disease (odds ratio, OR = 1.8, 95% CL 1.3 – 2.2), as were higher levels of the biomarker. In addition, C reactive protein levels were also significantly associated with more severe disease (OR = 1.8, 95% CI 1.3–2.6). Using the area under the receiver operating curve for procalcitonin, the predictive value was 0.76.

Commenting on their results, the authors noted that procalcitonin demonstrated the highest discriminatory power between severe and non-severe COVID-19. Although only a small number of COVID-19 patients (1.4%) had a bacterial co-infection, the authors concluded that measurement of procalcitonin levels appeared to be a promising approach to help clinicians recognise patients a higher risk of more severe COVID-19 infection.

Citation
Kaal A et al. Diagnostic yield of bacteriological tests and predictors of severe outcome in adult patients with COVID-19 presenting to the emergency department. Emerg Med J 2021

Omega-3 supplements reduce markers of inflammation in response to stress

27th April 2021

Supplementing with fish oils appears to offer some level of protection against cardiovascular disease but whether this effect arises through blunting the stress responsive system is unclear.

In a large, prospective study of nearly half a million individuals, higher intakes of fish intake were associated with a reduced all-cause mortality. One factor associated with biological ageing is the length of telomeres, which are strands of DNA at the ends of chromosomes and there is good evidence that telomere shortening is associated with increased mortality and how among individuals who consume higher amounts of omega-3 fatty acids, there is a reduced risk of telomere shortening. Moreover, increased physiological stress is a risk factor for many physical and mental health diseases and again, there is a suggestion that the pro-inflammatory response to psychological stress is attenuated to some extent by omega-3 fatty acids. Taken together, these results suggest that supplementing with omega-3 fatty acids may positively impact on markers of stress reactivity. This was the hypothesis considered by a team from the Institute for Behaviour Medicine Research, the Ohio State University College of Medicine, Ohio, US who examined a group of individual’s response to a social stress test. The team randomised participants into three groups who received either 2.5g/day, 1.25g/day of omega-3 or placebo for 4 months. At baseline, all participants were required to undergo the stress test which involved delivering a 5-minute speech without the use of aids or notes. Both saliva and blood samples were collected before the stress test and at 0.75, 1.25, 1.75 and 2 hours after and the test repeated at the end of the study. Parameters evaluated included cortisol, telomerase (an enzyme that maintains and restores telomeres) and several pro-inflammatory markers, interleukins 6, 10 and 12 as well as tumour necrosis factor (TNF). Participants were also required to score their anxiety levels before and after the test.

Findings
A total of 138 individuals were recruited (63% female) with a mean age of 51.1 years and with 72% of white ethnicity. Among those taking 2.5g/day of omega-3, their salvia cortisol levels were 19% lower throughout the final stress test compared to those given placebo (p = 0.01) although this difference was not significant for the 1.25g/day group. Similarly, the high dose supplement group had a 33% lower interleukin-6 level compared to placebo (p = 0.007). However, there were no differences with the other interleukin levels or of TNF. While telomerase levels remained unchanged in both supplement groups, levels dropped between 45 and 120 minutes after the stress test by 24%.

The authors commented on how 2.5g/day of omega-3 fatty acid supplementation blocked the stress-related decline in telomerase level as well as reducing levels of both cortisol and the pro-inflammatory interleukin-6 in a dose dependent manner. They suggested that omega-3 supplements had a unique stress-buffering effect on biomarkers of cellular ageing, concluding that while their data were preliminary, if replicated, it could limit the impact of repeated stress.

Citation
Madison AA et al. Omega-3 supplementation and stress reactivity of cellular ageing biomarkers: an ancillary sub-study of a randomised, controlled trial in midlife adults. Mol Psychiatry 2021.