• Post-acute coronavirus disease-19 (COVID-19) respiratory
symptoms are common and may be caused by a variety of factors
including, among others, cardiac and respiratory dysfunction.
• A detailed history and examination with appropriate investigations
is imperative to define the exact nature of the dysfunction.
• Limited data exist to guide evidence-based approaches to treatment.
• Injudicious use of corticosteroids is cautioned against as well as
indiscriminate use of off-label drugs

Calligaro, GL

Dheda, K

Feldman, C

Kalla, IS

Koegelenberg, CFN

Lalloo, U

Perumal, R

Richards, GA

Van Zyl-Smit, RN

Wong, M

LSHTM Research Online

 AJTCCM  VOL. 27  NO. 2  2021  72SATS NEWSExecutive summary• Post-acute coronavirus disease-19 (COVID-19) respiratory symptoms are common and may be caused by a variety of factors including, among others, cardiac and respiratory dysfunction.• A detailed history and examination with appropriate investigations is imperative to define the exact nature of the dysfunction.• Limited data exist to guide evidence-based approaches to treatment.• Injudicious use of corticosteroids is cautioned against as well as indiscriminate use of off-label drugs.Background and nomenclatureThe COVID-19 pandemic caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused significant mortality and morbidity in South Africa. The initial clinical focus was on the waves of acute disease and the focus has now shifted to those with post-COVID-19 symptoms and impairments. It is anticipated that COVID-19 will have a long-term impact on the physical, emotional, mental, cognitive, and social status of survivors.Most patients have mild COVID-19, while a minority of those with acute symptoms require hospitalisation (~10 - 15% depending on age and comorbidities), and only a fraction of these require intensive care support (~3 - 5% of those hospitalised). COVID-19 is responsible for considerable mortality in hospitalised patients, and those that survive may have significant ongoing health issues after discharge.[1-4] It is also now well recognised that many patients who did not require hospitalisation or intensive care support, may also have ongoing symptoms for weeks or months after the acute illness.[1-4] The spectrum of pulmonary involvement in COVID-19 is extensive, and the clinical and radiological presentation of severe COVID-19 pneumonia is variable. It is not yet known to what extent acute infection results in long term respiratory impairments nor the time course to potential resolution.[5-7] These are often referred to as post-COVID-19 lung disease, long-COVID, or COVID-19 pulmonary fibrosis/ post-COVID-19 organising pneumonia. More recently, the term post-acute sequelae of SARS-CoV-2 infection (PASC) has been used as an umbrella term to collectively describe these effects. There are currently no clinical trials to provide high-quality data to guide the clinical care of this growing patient population[8]. The South African Thoracic Society position statement on post-COVID lung disease is to assist clinicians in managing patients with persistent respiratory symptoms following proven or suspected COVID-19.RecommendationsWe recommend the following:1.  Patients who required intensive care or ventilatory support (including high flow nasal oxygen) may have residual respiratory symptoms and deficits.[5,7] Follow-up with a specialist physician or pulmonologist is advised.2.  Post-acute respiratory distress syndrome pulmonary fibrosis is a well-recognised condition and responds poorly to available medical therapies.[9] Follow-up with a specialist physician or pulmonologist is advised. 3.  Organising pneumonia is a clinical entity usually diagnosed on histology, together with compatible radiology, and upon the exclusion of an ongoing infectious process. This condition generally responds well to oral corticosteroids but is diagnosed by exclusion and should not be made using radiology alone.[10,11] Patients with radiological features of organising pneumonia should be referred to a pulmonologist for further investigation, multidisciplinary team discussion, and consideration of therapeutic interventions. 4.  SARS-CoV-2 infection may result in prolonged cardiovascular, neurocognitive, and psychiatric problems. Patients with persistent symptoms (>3 months) should be referred to the appropriate specialist for further investigation.[12] 5.  Fatigue is a common symptom following both mild and severe COVID-19 and may be multifactorial in aetiology. Patients with persistent fatigue (>3 months) should be investigated broadly before attributing fatigue to respiratory deficits.[12,13] A referral to a specialist physician is advised. 6.  There are no proven therapies for post-COVID-19 lung disease. Referral of patients to specialist units or to units undertaking clinical trials is advised. The use of experimental/unproven therapies should only be considered by specialist respiratory units, those doing clinical trials, or multidisciplinary teams. 7.  Evidence for the use of corticosteroids is limited but their use may be appropriate in a subset of patients with persistent, non-improving South African Thoracic Society position statement on post-acute sequelae of SARS-CoV-2 infectionR N Van Zyl-Smit,1, MB ChB, FRCP (UK), Dip HIV (Man), MMed, FCP (SA), Cert Pulm (SA), PhD, ATSF;  G L Calligaro,1 BSc Hons (Phys), MB BCh, Dip PEC (SA), MMed, FCP (SA), Cert Pulm (SA);  K Dheda,1 MB ChB, FCP (SA), FCCP, FRCP, PhD; C Feldman,2 MB BCh, FCP (SA), FRCP, PhD, DSc;  I S Kalla,2 MB BCh, PhD, FCP (SA), FCCP (USA), Cert Pulm (SA), Cert Crit Care (SA);  C F N Koegelenberg,3 MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulm (SA), PhD;  U Lalloo,4 MB ChB, FCP (SA), MD, DOH, FCCP, FRCP; R Perumal,1 MB ChB, MPH, MMed, FCP (SA), Cert Pulm (SA);  G A Richards,2 MB BCh, FCP (SA), FRCP, PhD; M Wong,2 MB BCh, DCH (SA), FCP (SA), FCCP, FRCP 1 Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, South Africa2 Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa3 Division of Pulmonology, Department of Medicine, Stellenbosch University, Cape Town, South Africa4 Life Mount Edgecombe Hospital, Durban, South AfricaThis open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. AJTCCM  VOL. 27  NO. 2  2021  73SATS NEWSsymptoms, in the presence of a multidisciplinary team-confirmed interstitial lung disease and objective impairment in lung function.[14] 8.  Clinical details should be comprehensively recorded, decision-making should be rational and carefully documented, and patients should be closely monitored. The injudicious use of high-dose prolonged courses of corticosteroids, immunomodulatory drugs such as azithromycin, or antifibrotic agents such as pirfenidone, is discouraged. WorkupSuggestions for initial workup:1.  A detailed history of pre-COVID-19 clinical status, comorbidities, effort tolerance, functional status, in addition to medication and smoking history should be ascertained. 2.  A SARS-CoV-2 PCR should ideally be performed and confirmed to be negative prior to physiological testing (lung function/6-minute walk/exercise test etc.) in accordance with infection prevention and control policies and guidelines. Patients may have persistent positive PCR of uncertain significance and while ongoing infectiousness is unlikely, staff/patient safety must be prioritised[15]. 3.  Stress-testing, sub-maximal exercise testing, and maximal exercise testing should be used with caution within 3 months of the acute illness due to the risk of exacerbating fatigue, myositis, and myocarditis. 4.  A thorough clinical and laboratory evaluation should be performed for common causes of fatigue, including an evaluation of sleep and mental health changes, haemoglobin, thyroid function, renal function, creatinine kinase, and glycated haemoglobin A1C.[1,16]5.  An electrocardiogram, spirometry, pulse oximetry and chest radiograph are recommended for the initial investigation of persistent respiratory or cardiovascular symptoms.[12-14]6.  Specialised investigation with high resolution computerised tomography (CT), CT pulmonary angiography, echocardiography, coronary angiography, and neurocognitive studies should be considered for patients with persistent symptoms (>3 months) who are not on an improving clinical trajectory, or in whom initial testing (as above) warrants further specialist investigation. Bronchoscopy with lavage and biopsies should also be considered where indicated.[10,11,17]1. Al-Aly Z, Xie Y, Bowe B. High-dimensional characterisation of post-acute sequelae of COVID-19. Nature 2021 (epub 22 April 2021). https://doi.org/10.1038/S41586-021-03553-92. Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: Retrospective cohort study. BMJ 2021;373:n1098. https://doi.org/10.1136/bmj.n1098 3. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet 2021;397(10270):220-232. https://doi.org/10.1016/S0140-6736(20)32656-8. 4. Morin L, Savale L, Pham T, et al. Four-month clinical status of a cohort of patients after hospitalisation for COVID-19. JAMA 2021;325(15):1525-1534. https://doi:10.1001/JAMA.2021.3331 5. Han X, Cao Y, Jiang N, et al. Novel coronavirus disease 2019 (COVID-19) pneumonia progression course in 17 discharged patients: Comparison of clinical and thin-section computed tomography features during recovery. Clin Infect Dis 2020;71(15):723-731. https://doi:10.1093/cid/ciaa271 6. Torres-Castro R, Vasconcello-Castillo L, Alsina-Restoy X, et al. Respiratory function in patients post-infection by COVID-19: A systematic review and meta-analysis. Pulmonology 2020. https://doi.1016/j.pilmoe.2020.10.013  7. Wu X, Liu X, Zhou Y, et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: A prospective study. Lancet Respir Med 2021 (epub 05 May 2021). https://doi.org/10.1016/S2213-2600(21)00174-0 8. Lechowicz K, Drożdżal S, Machaj F, et al. COVID-19: The potential treatment of pulmonary fibrosis associated with SARS-CoV-2 Infection. J Clin Med 2020;9(6):1917. https://doi:10.3390/jcm9061917 9. Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: Mechanisms and clinical significance. Eur Respir J 2014;43(1):276-285. https://doi:10.1183/09031936.0019641210. Wang Y, Jin C, Wu CC, et al. Organising pneumonia of COVID-19: Time-dependent evolution and outcome in CT findings. PLoS ONE 2020;15(11):e0240347. https://doi.org/10.1371/journal.pone.0240347  11. Kory P, Kanne JP. SARS-CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’. BMJ Open Respir Res 2020;7(1):e000724. https://doi:10.1136/bmjresp-2020-000724    12. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute COVID-19 in primary care. BMJ 2020;370:m3026. https://doi.org/10.1136/bmj.m302613. Lutchmansingh DD, Knauert MP, Antin-Ozerkis DE, et al. A clinic blueprint for post-coronavirus disease 2019 recovery: Learning from the past, looking to the future. Chest 2021;159(3):949-958. https://doi:10.1016/j.chest.2020.10.067 14. Myall KJ, Mukherjee B, Castanheira AM, et al. Persistent Post-COVID-19 interstitial lung disease. An observational study of corticosteroid treatment. Ann Am Thorac Soc 2021;18(5):799-806. https://doi:10.1513/AnnalsATS.202008-1002OC 15. Jefferson T, Spencer EA, Brassey J, Heneghan C. Viral cultures for COVID-19 infectious potential assessment – a systematic review. Clin Infect Dis 2020:ciaa1764. https://doi:10.1093/cid/ciaa1763 16. Ayoubkhani D, Khunti K, Nafilyan V, et al. Post-COVID syndrome in individuals admitted to hospital with COVID-19: Retrospective cohort study. BMJ 2021;372:n693. https://doi.org/10.1136/bmj.n69317. Copin MC, Parmentier E, Duburcq T, Poissy J, Mathieu D. Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection. Intensive Care Med 2020;46(6):1124-1126. https://doi:10.1007/s00134-020-06057-8

South african thoracic society position statement on post-acute sequelae of SARS-CoV-2 infection

https://researchonline.lshtm.ac.uk/id/eprint/4663707/1/341-949-1-PB.pdf

South african thoracic society position statement on post-acute sequelae of SARS-CoV-2 infection

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