Fidelity, tolerability and safety of acute high-intensity interval training after hospitalisation for COVID-19: a randomised cross-over trial

Introduction

It has become increasingly clear that a substantial proportion of patients suffering from COVID-19 develop so-called ‘long COVID-19’, that is, often invalidating symptoms including dyspnoea, chest pain, exercise intolerance and extreme fatigue, to mention a few, all of which persist way beyond the acute viral infection.1–4 The underlying mechanisms of long COVID-19 are unknown but likely involve residual inflammation in the heart, lungs and vasculature.5 While the need for implementing evidence-based rehabilitation schemes that include exercise training following COVID-19 is imminent, no consensus exists as to how such programmes should be designed.

It is widely appreciated that high-intensity interval training (HIIT) promotes greater health-related benefits than traditional moderate-intensity training in various patient populations despite a reduced time commitment.6–8 However, in the context of COVID-19 rehabilitation and long COVID-19 prevention, it has emerged as a particularly controversial training modality. Hence, several opinion papers and guidelines favour low-intensity exercise with gradual increases in intensity, mostly due to safety concerns.6 9–15 There is nonetheless currently no firm evidence base to argue in favour of this. A recent retrospective study on 28 discharged COVID-19 survivors conversely concluded that HIIT might safely be performed in these patients.16 Furthermore, in contrast to low-intensity and classical endurance exercise training, HIIT may more specifically target residual vascular inflammation, a putative central mechanism of long COVID-19.5 However, it is unknown to which extent it is feasible to implement HIIT in recently discharged patients with COVID-19, that is, whether they can tolerate HIIT without adverse effects.

In the present study, we assessed the fidelity, tolerability and safety of three widely used HIIT schemes in individuals recently discharged after hospitalisation for severe COVID-19.

Methods

Results

The study flow diagram is shown in figure 1. A total of 10 participants were enrolled and randomised and complied with the three HIIT protocols, and all participants were thus included in the analysis (attendance 100%). Baseline characteristics, including lung function and PFASS scores, are presented in table 3. All participants except for one with a restrictive pattern had normal ventilatory capacity, while five had reduced diffusing capacity (mild reduction in three cases, moderate-to-severe in two cases). Generally, the participants were only mildly to slightly affected by persisting COVID-19 symptoms according to PFASS scores, with the highest score of 3 in one individual. The primary reason for not participating was feeling too weak to exercise after the infection.

Outcomes of the three HIIT training protocols were compared by a red-amber-green design (table 2). No ‘red’ training sessions occurred, and only 1/10 training session in 4×4 was amber due to a low Likert score (tolerable: 3/10), and 1/10 in the 10-20-30 was amber due to inadequate time spent >85% of HR_max as prescribed. The rest of the training sessions were reported as green, which means all three HIIT protocols are tolerable and safe (figure 2). No adverse events were reported during the study, and no angina or ECG changes were seen after HIIT training.

There was a between-protocol difference in terms of the exercise intensity when dichotomously assessing for time spent with a heart rate ≥85% of HR_max (figure 3A). In contrast, tolerability as assessed by Likert scale scores (figure 3B) and RPE (4×4; 5 (2), 6×1; 5 (2), 10-20-30; 6 (2); p=0.28) did not differ between protocols. When considering HR and RPE changes non-dichotomously, largely similar objective and subjective measures of intensities were observed throughout each protocol (online supplemental figures 1 and 2).

Discussion

This study compared the fidelity, tolerability and safety of three HIIT protocols conducted on individuals recently hospitalised with COVID-19. Our findings indicate that HIIT is feasible regarding fidelity, tolerability and safety, regardless of the specific protocol.

No adverse events occurred in any of the HIIT protocols. These results are in line with a previous study on COVID-19 survivors,16 as well as several studies on other ‘high risk’ patient groups such as ischaemic heart disease and heart failure in whom it is considered safe.6 22 Thus, we consider it unlikely that HIIT should be associated with a high risk of acute adverse cardiovascular events. This concern was raised in The Stanford Consensus Statement for Post-COVID-19 Rehabilitation as one of the primary arguments against HIIT use in these individuals.23 However, studies with regular exercise are needed to determine the long-term safety of HIIT in this context.

We found that while all three HIIT protocols were well tolerated, the greatest intensity, given by the time spent above 85% of HR_max, was achieved by 4×4. Time spent above 85% of HR_max was chosen since HIIT is widely defined as training intensities at 85%–90% of HR_max.7 24 The cut-off, 85% of HR_max, is arbitrarily defined, and the supplemental graphic overview shows that all protocols performed well with high RPE and HR reaching maximum in all protocols. These findings, combined with the strong physiological rationale for HIIT, highlight it as an attractive option for COVID-19 rehabilitation. This is further invigorated when considering the widespread and disease-specific vascular inflammation in COVID-19 that persists after the acute viral infection and which is thought to contribute to the very diverse cluster of symptoms associated with long COVID-19.25 Potentially, this may be specifically counteracted with HIIT, where the pronounced changes in vascular shear stress that occur between intervals combined with the effects of anti-inflammatory myokines that are released from working skeletal muscle in an intensity-dependent manner may enhance endothelial repair and dampen proinflammatory processes within the vascular wall.5

The high composite intensity achieved is the best-documented means for increasing maximal oxygen consumption (V̇O_2max) and exerting beneficial cardiovascular effects. HIIT has thus been reported to be superior to continuous endurance training in several patient groups.7 26 These include patients with hypertension, ischaemic heart disease and heart failure, in which V̇O_2max has furthermore been noted as the single best predictor of mortality.27 28 It remains to be determined whether this is also the case in various lung diseases, such as chronic obstructive pulmonary disease. Still, HIIT has been noted to be associated with higher adherence in these patients, conceivably because the intermittent nature of HIIT reduces ventilatory demand and thus exertional dyspnoea and perceived breathing effort.29 30 This may also apply to patients recovering from COVID-19. Even though the present study is small scale in this context, and larger randomised controlled studies are warranted, we posit that HIIT should also be considered among the preferred training modalities in the rehabilitation post-COVID-19.

A strength of the study is the randomised sequence of the exercise training protocols, which eliminated systematic carry-over effects of the previous training protocol. Another strength is that this is the first study testing HIIT protocols post-COVID-19 in a supervised manner. Moreover, our research investigated the fidelity, tolerable and safety of three various HIIT protocols with different work or intensity periods, thus enabling between-protocol comparisons.

Some limitations should be considered when interpreting the results of this study. First, our results may be affected by selection bias because the main reason for declining participation was feeling too weak to exercise, which may indeed be a symptom of long COVID-19. Our results regarding fidelity and tolerability may thus have been different if we had studied these patients, which arguably represent the group that may benefit the most from targeted rehabilitation. Another important limitation is the small study size (n=10) which limits the conclusions, particularly when considering the heterogeneity of the participants. Furthermore, we only tested the fidelity, tolerability and safety to acute HIIT and cannot draw any firm conclusions regarding training over extended periods. Even though we expect a HIIT-based rehabilitation scheme over an extended period to be feasible, this remains speculative.

In conclusion, we found that individuals recently recovered from COVID-19 could successfully and safely complete three acute bouts of the most widely used HIIT protocols. Our findings highlight that HIIT should be evaluated as a rehabilitation strategy for post-COVID-19 in future randomised controlled trials.