Post-COVID Recommendations for primary care physicians
Introduction and general overview
During the COVID-19 pandemic, various efforts led to the creation of post-COVID consultation clinics, research cohorts, online information platforms, and associations of patients with post-COVID condition in Switzerland. This current work mandated by the Federal Office of Public Health and supported by the Swiss Medical Association (FMH), aimed to establish recommendations for primary care physicians on post-COVID condition. This work was based on an initial document created by the Geneva University Hospitals on post-COVID condition (18). The division of primary care medicine at the Geneva University Hospitals and the division of neurology at Inselspital (Bern University Hospitals), steered this work with the contribution of several experts and patients nationwide. A sounding board and working groups were created to establish these recommendations, which were validated by the national Swiss scientific and medical societies.
This document should be used by primary care physicians to guide them in the diagnosis and management of post-COVID condition. The pathway provides a general overview of a patient’s care pathway and indicates when to refer the patient to specialized consultations or to rehabilitation. The summary provides a general overview of the clinical assessment, scales, investigations and treatment options. The summary can be used as a quick guide to care for post-COVID condition. A symptom-based approach is provided in the full document with recommendations on the assessment, investigations and management approaches for each symptom. While post-COVID condition is a systemic condition that manifests with several symptoms at once, the symptom-based approach helps physicians find the information quickly and efficiently. A complete overview of the full recommendations is highly recommended as it the most comprehensive way to understand and follow the recommendations.
A significant proportion of patients infected by SARS-CoV-2 present symptoms that persist for several weeks (19) or even years after the infection (20). Patients can experience a range of symptoms, including persistent fatigue; post-exertional malaise; cognitive impairment; dyspnea; pain; and cardiac, digestive, or psychiatric disorders. Symptoms vary in terms of presentation and intensity and can also fluctuate over time. Persistent symptoms after SARS-CoV-2 infection are referred to as post-COVID condition (21), Post- acute sequelae of SARS-CoV-2 (22) (PASC) or Long COVID (21).
On October 6, 2021, the World Health Organization published a definition of post-COVID condition (23).
The diagnosis of post-COVID condition relies on the WHO definition. Tests confirming a SARS-CoV-2 infection are a reverse transcriptase polymerase chain reaction (RT-PCR) or antigenic test during the acute phase, or anti-N antibodies (serological test) documenting natural immunity. Cellular tests are not recommended at this stage due to the absence of standardization of these tests and risks of cross-reactivity.
A probable SARS-CoV-2 infection is based on clinical judgment and disease progression; however, it is also important to note that other diseases could be linked to similar symptoms.
Two main subtypes of post-acute sequelae of SARS-CoV-2 have been identified to date:
- Patients with post-viral symptoms including fatigue, post-exertional malaise, cognitive impairment among others. These patients are mostly treated as outpatients and do not require hospitalization; however, the symptoms have a significant impact on their functional capacity and quality of life.
- Patients who are hospitalized or treated in the intensive care unit, who might experience end-organ damage, and specific post-acute sequelae of SARS-CoV-2
This document addresses the first subtype of patients and does not address post-hospitalization or post-intensive care sequelae. Specific guidelines for patients who might have pulmonary sequelae (post-hospitalization) have been addressed by the Swiss Society of Pulmonology (16). Patients who have had a stay in the intensive care unit (ICU) should benefit from an interdisciplinary post-ICU follow-up.
Post-COVID condition’s underlying mechanisms have yet to be identified, but some studies suggest a potential immune dysregulation and persistent inflammatory state (24, 25), endothelial dysfunction leading to microthrombosis (26) or the persistence of viral particles (27). While these mechanisms have not been proven yet, they could affect all systems in the body, including the autonomic nervous system (28, 29), leading to the wide range of symptoms in post-COVID condition. In a proportion of patients with post-COVID condition, symptoms become chronic and have a significant impact on functional capacity and quality of life, drawing parallels with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In these cases, suggested approaches for post-COVID condition could benefit patients with ME/CFS, and increasing knowledge on post-COVID condition could help better understand ME/CFS.
Initial medical assessment
The acute and post-acute phases of the disease as well as the various reasons behind the symptoms and their impact should be considered in cases of suspected post-COVID condition. The following general guidelines can be used:
- Assessment of the acute phase of the infection (first 10 days after symptom onset) with identification of the signs and symptoms at that time, the various tests already carried out (PCR, serology, imaging, electrocardiogram, laboratory testing) the different treatments used (paracetamol, ibuprofen, vitamins, corticosteroids, monoclonal antibody treatment, inhalation sprays and integrative medicine, etc.) as well as the various consultations or follow-ups. An interdisciplinary management approach is essential for patients presenting post-COVID condition who may present several persistent symptoms concomitantly.
- Assessment of the post-acute phase (fluctuation of symptoms) as well as the current phase, reviewing all symptoms potentially linked to post-COVID condition.
- Assessment of other reasons or multifactorial causes for the symptoms by reviewing all history (personal and family), treatments, lifestyle, and patients' perception of the disease.
- Assessment of determinants and risk factors: increased risk of post-COVID condition
- Female sex (30, 31)
- Number of symptoms in the acute phase (32)
- Pre-existing comorbidities such as hypertension (33), diabetes (34), asthma (35), obesity (35, 36); and lipid metabolism disorders (36). It is not clear to date if these pre-existing comorbidities are associated with post-COVID condition only in patients who have had a severe acute phase of the disease, as studies have evaluated large cohorts without separating inpatients and outpatients
- Depression is associated with an increased risk of developing chronic symptoms (20)
- Assessment of determinants and risk factors: decreased risk of post-COVID condition
- Vaccination (37)
- Omicron variants (38, 39)
- Assessment of physical activity, functional capacity and quality of life compared to prior to the infection in the social, family, personal and professional areas of life.
Evaluation and management in this document are addressed using a symptom-based approach, however post-COVID condition could be the manifestation of a dysregulated autonomic system (29, 40) and a global approach is recommended for patients with post-COVID condition.
The question of the role of SARS-CoV-2 vaccination on the risk of post-COVID and post-COVID symptoms is very common in clinical practice. The evidence is still limited.
There is no evidence for a worsening of post-COVID condition following vaccination and there are no contraindications to vaccination specific to patients with post-COVID condition. It is also very important to increase patient awareness of SARS-CoV-2 vaccination in view of the preventive effect and the decreased risk of post-COVID condition.
Post-COVID in children (adolescents)
Adolescents – and to a lesser extent younger children – are susceptible to post-COVID condition (50). Even though this disorder is less common than in adults, raising awareness of pediatric post-COVID condition is crucial. The reported prevalence in children varies considerably between studies, ranging from 4% to 66% (51). The variability is due to study design heterogeneities in patients’ age, acute COVID-19 severity, outcome measurements, contexts (inpatient or outpatient), and data collection methods. In studies including SARS-CoV-2 negative controls, the reported prevalence of symptoms compatible with post-COVID disorder ranges from 2% to 9% in most studies, compared to 1%-10% in controls (50, 51). Risk factors for pediatric post-COVID are female sex, teenagers compared to younger children, chronic comorbidities (52), and lower socio-economic status (50).
As in adults, the most common symptoms of pediatric post-COVID are fatigue, headache, cognitive impairment, myalgia/arthralgia, dyspnea, and anosmia (52). Abdominal symptoms such as abdominal pain – and to a lesser extent constipation, diarrhea, nausea and vomiting – are also common in children (50).
The main concerns for children and adolescents with post-COVID condition are the educational impact and the risk of social withdrawal. The timely detection of red flags such as school withdrawal or failure, social isolation and anxiety is very important to minimize the impact on the child/adolescent’s development. Therefore, a global and interdisciplinary management approach in close collaboration with the educational network is necessary.
The management of pediatric post-COVID condition can be extrapolated from that of adult post-COVID condition, while considering the following specificities:
- School attendance and performance are frequently impacted in pediatric post-COVID condition. Therefore, an interdisciplinary approach in partnership with the educational setting (school, workplace) is of paramount importance to progressively implement the most suitable and safe program for maintenance and/or reintegration in the educational environment. Establishing goals and milestones that consider the patient’s functional and study capacity (adapted to their symptoms: fatigue, post-exertional malaise, cognitive impairment) is suggested for the reintegration in the educational setting and in the social network. The same approach applies to sports and physical activity. Considering physical activity, pacing and adapted rehabilitation programs are cornerstones in the management of pediatric post-COVID condition.
- As evidenced by controlled prevalence studies, and given the low specificity of commonly reported symptoms, not all symptoms can be attributed to SARS-CoV-2 infection. Other factors such as the psychological impact of the pandemic should be considered, especially in teenagers where physiological behavioral and hormonal changes can also contribute to some of the reported symptoms. Alternative diagnoses need to be ruled out, such as mood disorders, addictions (e.g., substance abuse, social media addiction). These conditions could be pre-existing or unmasked by SARS-CoV-2 infection. A major challenge is to distinguish mild or moderate post-COVID condition from the developmentally expected mood and energy variations of (early) adolescence. A detailed history comparing with siblings’ and friends’ developmental milestones may assist physicians in making the decision, as well as close and repeated follow-up. Post-exertional malaise can be a discriminating factor and help assess post-COVID condition compared to other types of fatigue or symptomatology.
- Most of the above-mentioned scales for screening and evaluation in adults have not been validated in the pediatric setting. Their use should be at the physician's discretion. Additionally, the use of pediatric questionnaires such as the Adolescent Depression Rating Scale (ADRS) (53) and the Pediatric Quality of Life Inventory (PedsQL) (54) can provide more pediatric-specific insights (55).
There is no pharmacological treatment for persistent symptoms following SARS-CoV-2 infection to date. There are several ongoing trials, evaluating potential treatments for post-COVID condition, including monoclonal antibodies (56), antiviral therapy (57), antihistamines (58), anticoagulation (58), and other therapies including pharmacological and non-pharmacological approaches (59, 60).
A global approach of evaluation and management should be considered, the various symptoms should be assessed, and interdisciplinary management and follow-up is recommended. As a general rule, management of daily energy reserve could reduce the exacerbation of most symptoms, once other causes have been ruled out.
A diary of daily energy levels (Appendix 2) is recommended to monitor changes in symptoms according to the 4P rule: Plan, Pace, Prioritize and Position. The daily routine is then adjusted to give priority to the activities that the individual considers as essential or a priority, while respecting the daily energy reserve. The diary can be used for evaluation and management.
Occupational therapy (ergotherapy) is recommended for implementing the 4P into the management of social roles and correlated activities.
Pacing: daily activities must be adapted and comply with individual energy levels to prevent post-exertional malaise, which would subsequently need a longer recovery period. It is therefore a question of "pacing" or resuming activity in a measured way, striking a balance between periods of activity and rest.
Graded exercise therapy or cognitive behavioral therapies are not recommended in post-COVID condition.
An integrative medicine approach with methods such as hypnosis, meditation, acupuncture, or vitamins is recommended for certain symptoms (vitamin B2 for example for headaches). Psychological support is important for symptoms such as anxiety, post-traumatic stress, and depression.
Experimental drugs or therapies are not recommended and need further evaluation before being suggested by primary care physicians.
The primary care physician remains the first point of contact for all patients.
Self-management with online resources such as https://www.rafael-postcovid.ch, https://www.altea-network.com, and https://www.long-covid-info.ch/ are online tools available for physicians, patients and their friends and family.
Interdisciplinary follow-up or a specialist consultation is recommended if symptoms do not improve after 3-6 months of follow-up or if symptoms are severely debilitating with functional impairment and worsening quality of life.
Post-COVID symptoms have a significant impact on functional capacity (social, personal, professional). A recent study in Geneva, Switzerland showed that SARS-CoV-2 infection doubled the risk of developing criteria for chronic fatigue syndrome and post-exertional malaise (68). Overall, 1.1% of individuals developed criteria for chronic fatigue syndrome after SARS-CoV-2 infection (68), and 8.2% had criteria for post-exertional malaise. Individuals with criteria for chronic fatigue syndrome or post-exertional malaise experienced long-term consequences, chronic functional impairment, and had a poorer quality of life (20, 68). Functional impairment was manifested by increased absenteeism, as well as reduced productivity (20, 68). A recent report estimated the losses attributed to post-COVID, with $170 billion attributed to lost wages alone (69) in the United States. Specific estimates are not available for Switzerland to date.
Physicians should ask patients to compare their functional capacity prior to the infection to their functional capacity after the infection, in all areas of life. Patients can be asked about the activities of a typical day prior to the infection, compared to their current state. The Sheehan disability scale (70) is a useful tool to assess functional capacity, and days lost or with reduced productivity. The Bell’s Chronic Fatigue and Immune Dysfunction Syndrome scale (CFIDS) can also be used to assess functional capacity, with 11 statements describing the level of symptoms scored from 0 to 100 (71). Patients choose one of the statements best describing their symptoms. Comparison to functional capacity and quality of life prior to the infection can help assess current symptoms and their impact on functional capacity and quality of life.
How can individuals return to work in the event of post-COVID condition?
The symptoms of post-COVID condition may persist for weeks or years, affecting functional and work/study capacity. Before planning a return to work/activity, patients should discuss this with their primary care physician, and be medically fit to resume the activity (work or otherwise). Returning to work can be difficult and may lead to apprehension and anxiety following long-term leave or in patients who are still symptomatic. This should be carefully discussed with the primary care physician and the employer to raise awareness of the employee's condition in the workplace, and to collaborate on the most suitable return to work plan for both employer and employee (72, 73). Regular meetings with the employer and follow-up with the primary care physician to discuss the return to work are recommended when the employee is ready to return to work.
Individuals with post-COVID condition generally present severe fatigue defined as asthenia, post-exertional malaise (exacerbated by physical or intellectual effort or increased stress), orthostatic intolerance, cognitive impairment with a difficulty to multitask or concentrate for long periods, or shortness of breath/chest pain or palpitations that can limit work, intellectual, and physical activity. Patients may wake up tired and spend most of the day operating with minimal energy levels. Individuals use their energy reserve to carry out all of their daily activities and in all aspects of their lives, including personal, professional and social. If overworked, individuals may experience post-exertional malaise and will need several days to recover.
Patients with post-COVID condition can usually identify a time of day when they have higher energy levels. It is important for employees and employers to consider reducing working hours and workload to ensure recovery, taking advantage of the time of day when the employee feels most capable to work or concentrate. The symptoms of post-COVID condition can also fluctuate and, ideally, employers could reconsider the workload on days when employees suffer a relapse or present significant symptoms such as post-exertional malaise. Patients should ideally reduce or completely remove workload on days with decreased energy levels (adapted response) to prevent post-exertional malaise as much as possible. Symptoms tend to improve over time (albeit slowly) if the recovery setting offers appropriate conditions for better recovery. A dialogue of trust between the primary care physician and the patient is essential to best identify the patient's functional capacity. A diary of daily energy levels (Appendix 2) is a recommended tool for patients to track their energy levels, review any improvements and determine when they are feeling better, which activities require greater energy expenditure, and how to plan ahead.
A phased return is recommended after setting realistic short-term objectives agreed between the employer and the employee. A phased return to work should initially be at a reduced percentage of the usual rate of activity, with a preference for partial days or a few hours per day, ideally aligned with the time of day when the person feels most energetic. Starting with single-task work while delegating other tasks to colleagues can help this phased return (72, 73). Restorative scheduled breaks can help maintain energy levels throughout the day and structure the working day. A blend of remote working and on-site work can help reduce the energy needed to commute, while helping the employee to re-integrate themselves within the team. Return to work arrangements (hours, rates) should allow patients to attend medical appointments. A return to work should not slow down the improvement of post-COVID condition. If a patient experiences post-exertional malaise or improvement stagnates, it is not advisable to increase the work hours. The work environment should be ergonomically adapted to help maintain energy levels (increased light or sound stimuli should be avoided, ergonomic workstation design: height adjustment, back support, etc.). Sometimes aids such as voice recognition tools/software can help to maintain energy levels (e.g., dictation) (72, 73).
Symptoms usually improve over time following a recovery process that is often slow. Unfortunately, a small percentage of patients with post-COVID condition may not recover sufficiently to return to work. A recent study in Geneva, Switzerland showed that 1.1% of individuals developed criteria for ME/CFS after SARS-CoV-2 infection (68), and 8.2% had criteria for post-exertional malaise. SARS-CoV-2 infection doubled the risk of developing criteria for chronic fatigue syndrome and post-exertional malaise (68).
Individuals who have functional impairment for more than 6 months should be referred to the social disability insurance, occupational health (ergotherapy) specialists, human resources and their primary care physician as well as post-COVID specialists to determine if recovering their functional capacity is possible or if long-term disability benefits are required.
The Swiss Insurance Medicine platform has established recommendations (74) and an online questionnaire (75) for physicians who are evaluating patients for insurance purposes.
Coordination is important between the primary care physician, the patient, the employer, and the disability insurance in such cases.