Introduction

The COVID-19 pandemic has resulted in an unprecedented strain on healthcare worldwide. Acute infection with early SARS-CoV-2 variants increases postoperative mortality and pulmonary complications, and indeed, this increased risk persists until around 7 weeks after the acute infection (COVIDSurg Collaborative, GlobalSurg Collaborative 2021). Additionally, those with persisting symptoms beyond 7 weeks have a significantly higher postoperative mortality rate than those whose symptoms have resolved (COVIDSurg Collaborative, GlobalSurg Collaborative 2021). Around 1 in 33 people in the UK report persistent symptoms following COVID-19 infection, termed ‘long COVID’ (Office For National Statistics 2023). Despite the significant prevalence and the potentially increased postoperative risk for those with persistent symptoms, there are currently limited guidelines on how best to pre-assess and manage these patients when they require surgery. This is complicated by the varied presentation of long COVID and inconsistencies in defining it. Whilst the UK Office of National Statistics defines long COVID as COVID-19 symptoms that have persisted for more than 4 weeks, the National Institute for Health and Care Excellence (NICE) describes the post-COVID-19 syndrome as symptoms continuing for more than 12 weeks, and there are multiple other time frames used internationally (Office For National Statistics 2023; National Institute for Health and Care Excellence 2021). Furthermore, although two of the most common symptoms include dyspnoea and fatigue, there are many others reported (Office For National Statistics 2023). Most, if not all, are non-specific. Therefore, developing guidelines for recognising, assessing and optimising these patients preoperatively is challenging.

Long COVID and chronic fatigue syndrome

Parallels between long COVID and myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and postural tachycardia syndrome (POTS) have been made in the literature (Lopez-Leon et al. 2021). Fatigue is the most frequently reported symptom in those with long COVID (Office For National Statistics 2023), which can be severe and debilitating, and the flares described are arguably similar to the relapses seen in ME/CFS. Unfortunately, there are no specific guidelines for the preoperative management of ME/CFS sufferers to help aid the development of something similar for long COVID. Indeed, whilst exercise programmes before major surgery can be beneficial in reducing postoperative morbidity (Wynter-Blyth and Moorthy 2017), NICE no longer recommends graded exercise therapy to patients with ME/CFS due to the minimal evidence supporting an improvement in symptoms, and in fact, many patients with ME/CFS report that it exacerbates their condition (National Institute for Health and Care Excellence 2021). Long COVID patients may pose similar complexities in terms of optimising their functional capacity before surgery. Long COVID patients also report symptoms of autonomic dysfunction as seen in POTS sufferers; again, perioperative guidelines for the latter are limited, but suggestions include preoperative intravenous hydration and the continuation of beneficial medications, such as beta blockers (Ruzieh et al. 2018).

Pathophysiology of long COVID

The pathophysiology of long COVID is a subject of ongoing research, and several hypotheses have been proposed. Given the diverse and multi-system presentation of long COVID, it is likely that the underlying process is complex and multimodal in nature. One theory attributes the symptomatology to the ongoing elevation of pro-inflammatory cytokines; levels of interleukin-1β, interleukin-6, tumour necrosis factor α (Schultheiß et al. 2022) and interferons (Phetsouphanh et al. 2022) correlate positively with long COVID symptoms 8 months after initial infection. Interestingly, the persistence of proteins from SARS-CoV-2 in long COVID sufferers has also been noted (Swank et al. 2022); perhaps this ongoing viral presence drives a chronic proinflammatory process in long COVID. Intriguingly, just as clinical parallels between long COVID and ME/CFS have been described, there is evidence that these diseases may also share common underlying mechanisms. Immune dysregulation may lead to the reactivation of certain viruses, such as the Epstein-Barr virus (Peluso et al. 2023); there is also some evidence of viral involvement in the development of ME/CFS (Ariza 2021). A persistently altered gut microbiome has been noted in long COVID patients (Liu et al. 2022), and gut dysbiosis is also described in ME/CFS (König et al. 2021). Additionally, evidence of endothelial dysfunction has been reported in both syndromes, with changes to the microcirculation potentially causing hypoperfusion and contributing to the exercise intolerance these patients experience (Haffke et al. 2022; Scherbakov et al. 2020). Perhaps the specific combination of these underlying processes influences the varied manifestation of long COVID in individual patients. Furthermore, it has been suggested that the hyperinflammatory state seen in SARS-CoV-2 infection may work synergistically with inflammatory changes that occur secondary to the surgical stress response (Noll et al. 2022). Understanding the mechanisms causing patients’ symptoms, particularly their exercise limitation, and how these mechanisms may be affected by surgery, may help elucidate how best to manage these patients perioperatively.

Long COVID appears heterogeneous in both its presentation and underlying pathology. Pulmonary function tests (PFT) and echocardiography are frequently used tools in anaesthetic pre-assessment. Dyspnoea is one of the more commonly reported long COVID symptoms, and patients with ongoing dyspnoea up to 3 months after non-critical COVID-19 have demonstrated lower forced vital capacity, forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide than those without dyspnoea (Cortés-Telles et al. 2021). They also had reduced functional capacity compared to their non-breathless counterparts, as measured by the 6-minute walk test (Cortés-Telles et al. 2021). PFTs may therefore be useful in the preoperative assessment of long COVID patients. Additionally, echocardiography may be helpful; 25% of 150 patients with long COVID symptoms, none of whom was hospitalised with COVID-19 or had pre-existing cardiovascular disease, had echocardiographic abnormalities at 4–12 weeks post-infection (Tudoran et al. 2021). Furthermore, there was a statistically significant correlation between the presence of echocardiographic abnormalities, the number of long COVID symptoms reported and a worse self-reported functional status (Tudoran et al. 2021). Conversely, studies have shown that long COVID patients with dyspnoea and fatigue can have normal PFTs and echocardiography, yet on cardiopulmonary exercise testing (CPET), there is demonstrable reduced peak aerobic capacity and impaired oxygen extraction almost a year after the initial infection (Singh et al. 2022). This suggests that perhaps our conventional pre-assessment of echocardiography and PFT could be of less value in a subset of long COVID patients, providing false reassurance of their cardiopulmonary function.

Existing guidelines — current scope and limitations

Multiple organisations worldwide have developed guidelines for patients with prior COVID-19 infection who subsequently require elective surgery (Noll et al. 2022; El-Boghdadly et al. 2022; Cortegiani et al. 2022; American Society of Anesthesiologists and Anesthesia Patient Safety Foundation 2022; Australian and New Zealand College of Anaesthetists 2022). As summarised in Table 1, these largely focus on the suggested time interval between infection and surgery and recommendations for preoperative assessment if surgery is required before this. The expert consensus from the UK, Italy and Germany advises delaying elective procedures until at least 7 weeks post-COVID-19 infection and until symptom resolution, due to the aforementioned increased risk of postoperative mortality and pulmonary complications (COVIDSurg Collaborative, GlobalSurg Collaborative 2021; Noll et al. 2022; El-Boghdadly et al. 2022; Cortegiani et al. 2022). However, the American Society of Anaesthesiologists (ASA) only recommends this delay for unvaccinated, asymptomatic patients, stating that there is insufficient evidence for those who have unresolved symptoms or are vaccinated and subsequently infected (American Society of Anesthesiologists and Anesthesia Patient Safety Foundation 2022). Indeed, the applicability of the early pandemic data which informed the suggested time delay has been questioned; less virulent COVID strains have since attained dominance, more efficacious treatments are available and a large proportion of the population has now been vaccinated (Lieberman et al. 2022). Furthermore, given that a significantly smaller proportion of COVID patients now require hospital or critical care admission than during the initial outbreak, they argue that recommendations regarding the timing of elective surgery need updating to reflect the current therapeutic landscape (Lieberman et al. 2022). However, postoperative outcomes were not directly investigated within this study, and whilst elective surgery may indeed be safer after a shorter delay for patients who have recovered from these less virulent strains, this remains speculative. Additionally, guidance on the timing of elective surgery for long COVID patients is limited, with organisations tentatively encouraging consideration of further delay beyond 7 weeks based on a multidisciplinary risk-versus-benefit discussion (El-Boghdadly et al. 2022; Cortegiani et al. 2022). Optimal timing will therefore depend on patients’ presenting symptoms and other comorbidities, balanced against their need for surgery and the likelihood of a prolonged delay worsening their functional status or quality of life.

Table 1 Summary of national organisations’ guidelines and consensus statements on post-COVID-19 patients requiring elective surgery
Full size table

Given the large spectrum of symptoms experienced by long COVID patients, in conjunction with a paucity of data on their postoperative outcomes, developing guidelines is complex. For those with recent COVID-19 infection, the Association of Anaesthetists consensus statement recommends assessing baseline perioperative risk using a validated risk assessment tool (e.g. Surgical Outcome Risk Tool (SORT)), optimising modifiable risk factors where possible and reaching a multidisciplinary decision based on these patient and surgical factors and considering patients’ additional COVID-19 risk (El-Boghdadly et al. 2022; Wong et al. 2020). However, these risk prediction models have not yet included long COVID in their online calculators as an independent predictor of risk. Without accurate risk prediction, having a comprehensive multidisciplinary discussion or obtaining informed patient consent is difficult. As part of their initial workup for suspected long COVID in primary care, patients should have had baseline blood tests (including full blood count, renal, liver and thyroid function tests, C-reactive protein, ferritin, D-dimer, glycated haemoglobin (HbA1c) and brain natriuretic peptide (BNP) and a resting ECG and chest x-ray (CXR) (National Institute for Health and Care Excellence 2021). Those with postural symptoms should also have had lying and standing blood pressures. An assessment of patients’ exercise tolerance, such as through a 6-minute walk test or by interrogation of their functional capacity using metabolic equivalents (METs) (Bossone et al. 2021), is required. Given the heterogeneity of the disease, it seems prudent to take a systems-based approach to further preoperative assessment. These initial steps could help identify patients that may benefit from onward specialist referral and additional preoperative investigations (such as PFTs and cardiac imaging). Functional capacity assessments such as CPET are not regularly undertaken in many NHS hospitals; perhaps referral for this could benefit those with persistent dyspnoea despite normal PFTs and echocardiography to better understand their exercise limitation and to aid quantification of their perioperative risks.

Whilst the majority of the above guidelines focus on preoperative assessment, other aspects of perioperative management for long COVID patients warrant consideration. In terms of the conduct of anaesthesia, avoiding a general anaesthetic in favour of regional or local techniques seems sensible where possible, particularly in those with severe respiratory pathology. This is also recommended for those with post-COVID-19 respiratory sequelae in consensus statements from organisations in the UK, Italy and India (El-Boghdadly et al. 2022; Cortegiani et al. 2022; Malhotra et al. 2021). Additionally, postoperative venous thromboembolism (VTE) is more common in patients with recent COVID-19, and those undergoing general anaesthesia may be at an increased risk (COVIDSurg Collaborative, GlobalSurg Collaborative 2022). Importantly, the risk of postoperative VTE was much greater in patients with ongoing COVID symptoms, even for those more than 7 weeks post-infection (COVIDSurg Collaborative, GlobalSurg Collaborative 2022). In conjunction with evidence that previous COVID-19 infection increases the risk of pulmonary embolism for up to 110 days post-infection (Katsoularis et al. 2022), it seems prudent to consider that long COVID patients may be at increased risk of VTE post-surgery. It is worth noting that, in the latter study, only 30% of the national population had had their first vaccine against COVID-19 by study completion, and Omicron had not yet become the prominent variant, so these findings may not be fully generalisable to the current immunity and virulence strains within the population (Katsoularis et al. 2022). The researchers additionally did not specifically investigate postoperative VTE or long COVID patients. Despite this, there is sufficient evidence to suggest that these patients may be at increased risk of postoperative VTE, yet prophylaxis strategies are not discussed in the majority of the above guidelines. Recommendations from the Australian and New Zealand College of Anaesthetists briefly suggest a discussion with haematology in this regard (Australian and New Zealand College of Anaesthetists 2022). It has been suggested by an expert consensus that patients up to 6 months post-COVID-19 infection should receive pharmacological thromboprophylaxis postoperatively, but how long this should be continued for has not been specified (Ferrandis et al. 2021). Finally, there is minimal guidance for determining the most appropriate postoperative destination for long COVID patients undergoing surgery. Perhaps having long COVID as a comorbidity should prompt perioperative clinicians to consider the need for high dependency level monitoring postoperatively. This should form part of a holistic assessment of other patient factors, surgical factors and the severity and nature of their long COVID symptoms.

Conclusion

In summary, long COVID is a heterogenous and increasingly common condition, and these patients may be at increased postoperative risk. The pathophysiology of long COVID is complex; a better understanding of the underlying mechanisms may help clinicians recognise how to best optimise these patients preoperatively and predict how they will respond to the surgical stress response. Developing guidelines for the preoperative assessment of these patients is challenging due to the diverse presentation of long COVID and the lack of data on postoperative outcomes for this cohort. Timing of elective surgery will likely need to be individualised for these patients, based on their constellation and severity of symptoms, their comorbidities and the complexity and urgency of the proposed surgery; shared decision-making will be required to consider the relative importance of these factors. Perioperative clinicians should take a systems-based approach to assessing these patients preoperatively to help determine whether additional discussions with specialists and further investigations would be beneficial, in addition to their existing primary care workup. Clinicians should additionally be cautious about the potentially increased risk of postoperative VTE in these patients and consider avoiding a general anaesthetic for those with severe respiratory sequelae. Patients and clinicians require prospective studies to help to quantify these risks, enable informed consent and ensure sound perioperative management to reduce the likelihood of adverse perioperative outcomes.