Long COVID: an evolving enigma

Key practice points:

• Long COVID can be diagnosed in patients with symptoms and signs of COVID-19 that continue for more than 12 weeks and are not explained by another diagnosis
• While long COVID is more common in those who experienced severe acute COVID-19, it can occur in any patient including those with a mild initial presentation, regardless of age
• The pathophysiology of long COVID is unclear and likely heterogeneous. It can be associated with a wide range of general and organ-specific symptoms and signs, which may occur in overlapping clusters, relapse and change over time. Common features include fatigue, difficulty concentrating (brain fog), chest pain or tightness, cough, breathlessness and other abnormal breathing patterns.
• There are currently no specific laboratory parameters diagnostic of long COVID. The diagnostic work-up will vary between patients but should broadly include:
  • A clinical history of their COVID-related illness, symptoms and how they were managed. Considering any pre-existing conditions and how they may be associated with or complicate presenting features.
  • Physical examination and further investigations tailored to the patient’s history and presenting features. Laboratory tests may help to provide further information and exclude other causes based on predominant symptoms; avoid requesting an excessive number of tests without indication.
  • Ruling out serious underlying organ damage
• Specific codes are available to record a diagnosis of long COVID in the patient record once alternative diagnoses have been excluded
• Most patients can be managed within primary care. The initial focus is achieving symptom control and identifying complications early. However, the care plan should also consider and address the wider consequences of ongoing symptoms, including effect(s) on quality of life, emotional distress and psychological implications for the patient and their family/whānau. Not adequately managing these factors can impede and prolong recovery.
  • All plans should include tailored education, self-care advice and realistic goals – all of which should be culturally appropriate
• There are currently no medicines indicated specifically for the treatment of long COVID (but numerous clinical trials are ongoing)
• Patients with complex presentations or persisting features are likely to benefit from multidisciplinary care involving allied health professionals, e.g. occupational therapists, physiotherapists, psychologists. There is currently no specific national funding for accessing these additional services, but work is ongoing to test the viability of regional care pathways (as of June, 2023).
• It is not possible to predict the time-course for recovery from long COVID; this depends on individual risk factors, as well as the severity and spectrum of symptoms. However, patients should be reassured that by adhering to management advice they will usually improve progressively over time.

Time-based criteria are used to distinguish long COVID-19

Long COVID (also referred to as long COVID-19, post-acute COVID-19 syndrome and post-acute sequelae SARS-CoV-2 infection [PASC]), is characterised by:^1–3

• Symptoms and signs consistent with COVID-19 that develop during or after an infection; and
• Continue for more than 12 weeks; and
• Are not explained by an alternative diagnosis

Long COVID is distinguished from “acute COVID-19” and “ongoing symptomatic COVID-19” according to the duration of symptoms and signs (Figure 1).^{1, 4} A positive SARS-CoV-2 test (i.e. RAT or PCR) at the time of assessment is not required for diagnosing long COVID,^{1, 4} assuming the patient has either: 1) a historical positive test result during the preceding COVID-19 phases (Figure 1); or 2) they meet the case definition and have a history indicative of probable infection, e.g. patient is a household or workplace close contact of someone with confirmed SARS-CoV-2 infection.

The pathophysiology of long COVID is currently unclear. In addition to possible organ damage caused during acute infection, other proposed mechanisms include ongoing chronic inflammatory processes, immune system dysfunction, viral persistence, endothelial dysfunction and microvascular blood clotting.^{5, 6} Psychological mechanisms have also been implicated as contributing and exacerbating factors.⁷ For example, psychological distress can be both a symptom and a risk factor for long COVID, and other presenting features can overlap with those caused by anxiety, e.g. fatigue, chest pain, difficulty concentrating.⁷

Even mild symptoms, if persistent, can have a substantial effect on a person’s quality of life, limiting their ability to engage in work, education and recreation.¹ More severe symptoms can cause significant functional impairment and, in some cases, may be a sign of serious underlying damage.^{5, 6}

For a comprehensive review on the pathophysiology and mechanisms of long COVID, see: https://www.nature.com/articles/s41579-022-00846-2

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Figure 1. Time-based distinction between different COVID-19 classifications.¹

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A closer look at prevalence and risk

It is estimated that 6 – 20% of people infected with SARS-CoV-2 worldwide experience features consistent with long COVID.^{8, 9} However, reported figures vary significantly between studies depending on the case definition and methodology used.

There is insufficient evidence to predict who will experience long COVID. It is more common among people with severe acute COVID-19, but can also occur in those who experienced mild-to-moderate symptoms.¹ Emerging evidence has highlighted other potential risk factors for long COVID, including female sex, high BMI, pre-existing co-morbidities (particularly asthma, hypertension or a psychiatric condition) and hospitalisation during acute COVID-19.^{6, 10, 11} However, given the evolving nature of this research, it is possible that proposed risk factors may be revised over time as further evidence emerges. For example, older age was initially suggested as a risk factor for long COVID based on evidence from individual studies;¹² a subsequent meta-analysis, however, did not confirm this association.¹¹

Research on long COVID in New Zealand is emerging

The prevalence of long COVID in New Zealand is not yet known as it is an evolving clinical diagnosis. There has been some preliminary study gathering data on people who self-identified as having long COVID. In the 2023 Ngā Kawekawe o Mate Korona study, approximately one in five people reported having symptoms that persisted more than three months after their acute infection,¹³ which is broadly consistent with international prevalence figures for long COVID.^{8, 9} Further robust investigation is required to derive quantitative prevalence data in New Zealand based on clinically confirmed diagnosis.

Qualitative findings of the Ngā Kawekawe o Mate Korona study give some insight into the experience of long COVID in New Zealand, demonstrating the wide-reaching impacts across all aspects of Hauora wellbeing, as well as people’s ability to engage in daily tasks and employment.¹³ Some survey participants described “how the illness had challenged their sense of identity”, forcing them to “make major changes in their lives and losing their sense of purpose”.¹³ Others emphasised the cultural impact that ongoing symptoms can have, such as “no longer being able to smell and taste food, so important to many aspects of tikanga Māori”.¹³

When to suspect long COVID

The most commonly reported persisting symptoms in people with long COVID include fatigue, difficulty concentrating (brain fog), chest pain or tightness, cough, breathlessness and other abnormal breathing patterns (Figure 2).^{1, 6, 14} However, more than 200 different symptoms and signs have been reported in the wider literature.^{6, 8} Features usually occur in overlapping clusters, that can fluctuate, change and relapse over time; they can affect any body system.^{1, 4} In some cases, symptom clusters are used to further define sub-classifications of long COVID, e.g. PASC-cardiovascular syndrome (PASC-CVS) which is a “heterogeneous disorder that includes widely ranging cardiovascular symptoms, without objective evidence of cardiovascular disease using standard diagnostic tests”.¹⁵ There can also be considerable overlap between the symptoms seen in long COVID presentations and those associated with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).^1,6

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Figure 2. Symptoms and signs associated with long COVID.^{1, 6, 14}

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There is no single diagnostic test for long COVID

For patients presenting in primary care with features suggestive of long COVID, a clinical history should be taken which includes identifying:^{3, 4}

• A history of acute COVID-19. There does not need to be a previous record of COVID-19 in the patient’s notes; it is sufficient to ask whether they have had COVID-19, either confirmed (e.g. with at-home RAT) or probable (e.g. having respiratory symptoms after being a close contact of a confirmed case). A negative RAT at the time of assessment does not exclude long COVID if the patient otherwise fits with the case definition.
• The type and severity of previous and current symptoms, including any factors that may trigger or exacerbate symptoms
• The timing and duration of symptoms since the patient’s acute COVID-19 phase
• Other pre-existing conditions which may explain or complicate the current presentation, and whether the symptoms and signs of these co-morbidities were exacerbated during the acute COVID-19 phase
• Any medicines used for the treatment of long COVID symptoms (including over-the-counter products) and whether hospitalisation was required during the acute COVID-19 phase (including details regarding management, complications, follow-up planned). N.B. there is not enough evidence to determine whether the use of antivirals during the acute COVID-19 phase reduces the risk of long COVID.
• Any mental health sequelae resulting from COVID-19 or its treatment; ask the patient how their symptoms have impacted on daily life, work, education and financial situation

Perform a general physical examination including pulse, blood pressure and oxygen saturation.^{3, 4} The need for other examinations is guided by specific symptoms and findings. For example:

• If cough and dyspnoea is present, perform chest auscultation
• If autonomic dysfunction is suspected, assess for postural hypotension/tachycardia
• If altered sense of taste or smell is present, examine the nasopharynx for other potential causes, e.g. nasal polyps, chronic rhinosinusitis
• If musculoskeletal issues are reported, assess the affected areas for tenderness and range of motion

Be selective when considering further investigations

If a more likely diagnosis is not revealed, the need for further investigations depends on the patient’s presenting features, history and examination findings.⁴ As a general rule, excessive testing should be avoided in the absence of red flags (see: “Situations requiring more urgent action”) as non-specific abnormalities are common following acute COVID-19 illness.

• If needed, baseline laboratory testing can be requested to expand on the clinical picture (e.g. FBC, creatinine/electrolytes, LFTs, CRP), with additional tests added based on reported symptoms to exclude other potential diagnoses (e.g. TSH and ferritin if fatigue is a concern).^{3, 17} Some studies indicate an increased risk of diabetes following COVID-19;¹⁸ while further information is required to support this relationship, HbA_1C testing can be included for select patients, e.g. those with other associated risk factors.

• Consider additional investigations in patients with predominant body system-specific symptoms, for example:^{3, 4, 16, 17}
  • Cardiovascular features – an ECG should be performed and further laboratory testing considered, e.g. brain natriuretic peptide (BNP) and troponin testing
  • Respiratory features – consider lung function/exercise tolerance testing, as appropriate. Spirometry and diffusion capacity testing are commonly suggested in the literature, however, access is variable across New Zealand. Chest X-ray may be useful in patients with significant breathing problems, particularly smokers or those with other respiratory co-morbidities (e.g. COPD, asthma).

Practice point: SNOMED CT, ICD-10 and other PMS codes for recording a diagnosis of long COVID can be found at: https://www.tewhatuora.govt.nz/for-the-health-sector/covid-19-information-for-health-professionals/recording-covid-19.

Management principles for patients with long COVID

A management plan for a patient with long COVID should aim to:^{1, 3}

• Achieve symptom control (once more serious pathology has been excluded)
• Identify any potential complications early
• Optimise the management of any pre-existing long-term conditions

Given the diverse spectrum of possible presentations, care pathways will differ considerably between patients. Table 2 provides a brief summary of primary care management recommendations for a patient with common long COVID features.

In addition to considering the physical aspects of rehabilitation, guidelines also emphasise that management should identify and address the wider consequences ongoing symptoms may have, including effect(s) on quality of life, emotional distress and psychological implications for the patient and their family/whānau (a “holistic” approach to care).^{1, 3, 4, 22} Evidence suggests that psychological and psychosocial factors can impede the rehabilitation process if they remain unaddressed or inadequately managed. For many patients, uncertainty associated with the underlying cause of long COVID and its recovery timeline (see: “Expected time to symptom resolution”) will be a major source of concern. Particular consideration also needs to be given to tailoring support for Māori and Pacific peoples (e.g. inclusion of family/whānau in the care plan), people with a disability, children and frail elderly people.¹

• Patient education and reassurance should be the foundation of any management plan. This information should be easily accessible, tailored to their level of health literacy and culturally appropriate.¹
  • A list of symptom-specific patient/whānau/carer education resources is available at: https://www.health.govt.nz/system/files/documents/publications/summary_of_symptoms_and_management_resources_for_people_and_whanau.v3.pdf. Other key general resources include Healthify, Unite against COVID-19, Te Whatu Ora Waitematā and Kids Health

• Encourage self-management. Once equipped with information and symptom recovery advice, patients should be encouraged to take an active role in their rehabilitation and apply self-management strategies where possible.³ Some patients may find it useful to track their symptoms using a diary to help identify patterns and changes over time.
  • An example of a symptom diary is available at: https://healthify.nz/tools/s/symptom-diary/

• Returning to work. Symptoms associated with long COVID can have a significant impact on a person’s capacity to engage in work;¹ patients should be advised to initiate discussions early with their employer to establish specific needs, and to plan for a gradual or phased return to work.^{23, 24} This may involve changes to the work environment and flexibility around working arrangements, e.g. reduced workload or hours, more frequent break times, remote working.^{23, 24} However, the capacity for such accommodations will depend on the specific employer and the type of work being undertaken. Clinicians can support patients by providing a medical certificate (if appropriate) and a letter outlining recommendations about return to work plans. If employees deplete all of their sick leave and annual leave, they may qualify for financial assistance from Work and Income (e.g. disability allowance) if they meet certain criteria.²⁴
  • For further information on how workplaces can support patients with long COVID in their return to work, see: https://www.waitematadhb.govt.nz/assets/Documents/clinics-services/LongCOVID/Workplace-support_Long-Covid_Final.pdf
  • For a perspective on accessing financial support through Work and Income for long COVID, refer to video #13 at: https://www.mesupport.org.nz/longcovidhelp
    Direct link to video: www.youtube.com/watch?v=_TZOvzBp0O4&t=344s

• Support for returning to school. For children and young people, consider the impact the ongoing symptoms may be having on their engagement in school/education; for those with a high absence rate, a progressive symptom-led return to classroom attendance should be encouraged, facilitated by options such as home-based, online or hybrid learning (if possible).¹
  • If required, support from a special education needs coordinator (SENCO) or Northern/Central/Southern Health School teacher may help to establish a tailored plan with the patient and their family/whānau.

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Table 2. General management recommendations for patients with long COVID in primary care. Adapted from Ministry of Health, 2022.^{1, 3, 25}

N.B. Links to selected external resources have been included. For a comprehensive list of resources to inform and support clinicians in applying these recommendations, see: https://www.health.govt.nz/system/files/documents/publications/summary_of_symptoms_and_management_resources_for_clinicians.v3.pdf

The importance of multidisciplinary care

Integrated multidisciplinary care is consistently highlighted in guidelines as being important for successful long COVID management.^{1, 4, 22} This approach can help to more effectively address the often wide array of long COVID symptoms that patients can experience, and may include a combination of in-person and telehealth services.⁴

Allied health professionals who can support the recovery of patients with long COVID in the community include:¹

• Occupational therapists – develop plans to achieve personal self-care, work and leisure objectives, including providing advice on pacing strategies and recommending adaptations to a patient’s equipment or environment
• Physiotherapists – focus on alleviating the physiological consequences of COVID-19. Physiotherapists interpret the findings of individualised assessments and help guide tailored rehabilitation programmes with specific physical interventions and exercise(s); they may be particularly useful when respiratory or musculoskeletal symptoms are a key ongoing issue.
• Clinical exercise physiologist – assess the causes of exercise intolerance or reduced functional capacity, and create individualised exercise-focused interventions to restore or alleviate loss of function
• Dietitians – assess the nutritional needs of a patient and create individual plans, taking into account other underlying conditions, swallowing difficulties, lifestyle, social or cultural factors. Particularly relevant in patients with ongoing poor appetite, unintentional weight loss or gastrointestinal symptoms.
• Speech language therapists – provide specialist assessment and rehabilitation for patients with communication or swallowing difficulties
• Psychologists – can help manage anxiety or distress, sleep disturbances, and provide coping strategies for processing the effects of ongoing symptoms
• Social workers – evaluate patient and family/whānau situations and needs according to their unique structural, economic, social and cultural challenges. This information can then be used to determine and prioritise goals that will promote wellbeing, resilience and ability to cope with stress.

Co-ordinating the transition between different care providers and settings is an evolving challenge in New Zealand. The Ministry of Health is continuing to develop long COVID rehabilitation guidance and its approach to service delivery; it is possible that more formal care pathways will be established once further evidence is available.

There is currently no national funding scheme for patients with long COVID requiring general practice consultations or allied health professional support, i.e. patients access services and are charged co-payments (as applicable) as for any other health condition.^{30, 31} Patients wanting timely access to allied health professional services will most likely have to self-fund appointments; this presents a significant barrier in achieving equitable health outcomes across patient groups.³⁰

Expected time to symptom resolution

There is no specific time course for recovery from long COVID; it appears to depend on individual risk factors (including psychological factors) and the severity and spectrum of symptoms experienced. In general, expected timeframes for recovery from COVID-19 specific symptoms are:¹

• Four weeks for myalgia, chest pain and sputum production
• Six weeks for cough and breathlessness to be significantly improved or resolved
• Three months for most other symptoms (fatigue often persists longer)
• Six months for all symptoms unless the patient had a complicated or prolonged admission to intensive care

In the absence of red flags, these timeframes can be used to guide follow-up, based on clinical judgement, with the proviso that patients schedule an appointment sooner if their condition deteriorates or they develop features that could mean referral or further investigation is required. Many regional HealthPathways recommend reviewing patients at 12 weeks if they are not improving with supported self-management.

The overall time to complete symptom resolution reported in the literature for patients with long COVID is highly variable. The largest meta-analysis currently available suggests that the average time to symptom resolution is four months in non-hospitalised patients with long COVID and nine months in those who required hospitalisation.⁹ However, in some cases symptoms can last significantly longer, with 15% of patients with long COVID continuing to experience symptoms at 12 months.⁹

Additional resources:

• Long COVID symptom map to help patients convey their symptom severity – https://www.health.govt.nz/system/files/documents/publications/hp8627-long-covid-symptom-map-version3.pdf
• ME support is a New Zealand support group for people with long COVID (or other post-viral illnesses such as ME/CFS) and their family/whānau. The website includes a series of videos to help explain the illness, manage associated symptoms and find support, along with in person and online support groups for members (membership is free) – https://www.mesupport.org.nz/longcovidhelp
• NHS patient resources:
  • Web-based information on recovering from long COVID – https://www.yourcovidrecovery.nhs.uk/i-think-i-have-long-covid/
  • NHS post COVID-19 patient information pack (N.B. Detailed and practical information but 24 pages if printing and some content may not be applicable to patients in New Zealand.) – https://gp-website-cdn-prod.s3.amazonaws.com/downloads/1589364822-a2ac4f0d54141da323f4087888276478.pdf