Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study, 2023, Podrug et al.

[SNT Gatchaman]

Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study
Podrug, Mario; Koren, Pjero; Dražić Maras, Edita; Podrug, Josip; Čulić, Viktor; Perissiou, Maria; Bruno, Rosa Maria; Mudnić, Ivana; Boban, Mladen; Jerončić, Ana

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored.

Individual pre and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2–3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6).

We found that various parameters of arterial stiffness and central hemodynamics—cfPWV, AIx@HR75, and cDBP as well as DBP and MAP—responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2–3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP).

The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

Link | PDF (Journal of Clinical Medicine)

 

[SNT Gatchaman]

32 patients standardised vascular assessments, pre- and post- mild Covid infection. The interesting part is the demonstration that vascular changes increased with time from infection.

responses to COVID-19 infection are dynamic and depend on the time since the onset of COVID-19 infection. We identified such time-dependent responses in the arterial stiffness parameters—cfPWV and AIx@HR75, the central hemodynamic parameter— cDBP, and the systemic hemodynamics parameters—DBP and MAP; and we showed that their values increased with the length of time that passed from the onset of COVID-19 infection, independent of age or other confounders.

The finding that the longer the period from COVID-19 infection the worse the vascular impairment was surprising, as we expected inflammation burden associated with COVID-19 to decrease with time.

The authors speculate that this could be due to development of auto-antibodies.

While we can only speculate on what causes this phenomenon, emerging evidence suggests that it stems from a failure to resolve autoantibodies observed during the acute phase of disease, or alternatively, that generating de novo pathogenic autoimmune responses post-recovery contributes to long COVID

 

[SNT Gatchaman]

The most validated and direct measure of arterial stiffness is the carotid–femoral pulse wave velocity (cfPWV) (Townsend, Wilkinson et al., 2015).

Figure 1 shows the normal rise in arterial stiffness associated with aging (b), compared with a similar change seen following Covid infection (a).

 

[Sean]

This is indeed an interesting result.

 

[Hutan]

Croatian research

When we looked to see if the mean individual pre–post changes were significantly different from 0, we found no significant pre–post change in any of the arterial stiffness or hemodynamic parameters tested (p ≥ 0.122).

So, for that way of assessing difference, they didn't find any difference in arterial stiffness between the pre and post-infection measurements. Have a look at Table 2. - it shows that the mean pre and post values for virtually all of the measures are very similar.


Figure 2 is the time since Covid infection against the change in arterial stiffness, normalised to a heart rate of 75 bpm. This is what they are reporting as the significant finding. There could be a relationship, but it's also possible it's just chance. The range of sampling was around 52 to 94 days after infection.

The 32 people aren't reported as having any post-Covid symptoms. I find it odd that the arterial stiffness gets worse over time in these healthy people. Even people with Long COVID tend, on average, to improve over time in that first year.

When I participated in a 2 xCPET experiment, my arterial stiffness was assessed (a brachial artery measure) and it came out significantly more stiff than would be expected for a woman of my age. I'm not sure that the arterial stiffness findings were ever published. The student who did the measure was quite nervous and I wasn't entirely sure if teh measurement had been done correctly. Part of that doubt might be me not wanting to believe that I have high arterial stiffness. Pre-ME/CFS I had been fairly fit, and even at the time of the CPETs, I still had a healthy BMI.

All that is to say, I think it's possible that an infection can have an impact on arterial stiffness. It was great that these authors thought to use the pre-Covid data they had to devise this study and I hope that there will be studies that track arterial stiffness after Covid-19 over time in people with Long Covid. But, I'm a bit hesitant to think this result will be replicated, in people with no Long Covid symptoms at least.

The finding that the longer the period from COVID-19 infection the worse the vascular impairment was surprising, as we expected inflammation burden associated with COVID-19 to decrease with time. While we can only speculate on what causes this phenomenon, emerging evidence suggests that it stems from a failure to resolve autoantibodies observed during the acute phase of disease [22,23,24], or alternatively, that generating de novo pathogenic autoimmune responses post-recovery contributes to long COVID with evidence of residual inflammatory cytokines [25,26,27].