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SARS-Cov-2 Organising Pneumonia: 'Has There Been a Widespread Failure to Identify and Treat This Prevalent Condition in COVID

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SARS-Cov-2 Organising Pneumonia: 'Has There Been a Widespread Failure to Identify and Treat This Prevalent Condition in COVID BMJ Open Resp Res: first published as 10.1136/bmjresp-2020-000724 on 22 September 2020. Downloaded from Perspective SARS- CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’ Pierre Kory ,1 Jeffrey P Kanne2 To cite: Kory P, Kanne JP. ABSTRACT We believe that clinicians have not sufficiently SARS- CoV-2 organising Reviews of COVID-19 CT imaging along with postmortem lung considered the condition of ‘viral- induced pneumonia: ‘Has there been a biopsies and autopsies indicate that the majority of patients secondary organising pneumonia (OP)’, largely widespread failure to identify with COVID-19 pulmonary involvement have secondary and treat this prevalent due to the fact that OP in its idiopathic form, organising pneumonia (OP) or its histological variant, acute called cryptogenic organising pneumonia condition in COVID-19?’. fibrinous and organising pneumonia, both well- known BMJ Open Resp Res complications of viral infections. Further, many publications on (COP), is a rare and clinically unique disease 2020;7:e000724. doi:10.1136/ often misunderstood and poorly recognised bmjresp-2020-000724 COVID-19 have debated the puzzling clinical characteristics of ‘silent hypoxemia’, ‘happy hypoxemics’ and ‘atypical ARDS’, even by pulmonologists. OP is a histological all features consistent with OP. The recent announcement pattern of lung injury characterised by the Received 20 July 2020 Revised 27 August 2020 that RECOVERY, a randomised controlled trial comparing filling of alveoli and alveolar ducts with spindle- Accepted 5 September 2020 dexamethasone to placebo in COVID-19, was terminated early shaped fibroblasts and myofibroblasts that later due to excess deaths in the control group further suggests form granulation tissue.4 However, OP more patients present with OP given that corticosteroid therapy is commonly results from infections (especially copyright. the first- line treatment. Although RECOVERY along with other viral), drugs or autoimmunity, when the term cohort studies report positive effects with corticosteroids on 5 morbidity and mortality of COVID-19, treatment approaches secondary OP applies. COP and secondary OP could be made more effective given that secondary OP often have indistinguishable clinical and radiographic requires prolonged duration and/or careful and monitored findings, relapse rates, mortality and robust 5 tapering of corticosteroid dose, with ‘pulse’ doses needed for responses to corticosteroid therapy. Viral- the well- described fulminant subtype. Increasing recognition of induced OP during the severe acute respira- this diagnosis will thus lead to more appropriate and effective tory syndrome (SARS), Middle East respiratory treatment strategies in COVID-19, which may lead to a further syndrome (MERS) and H1N1 viral pandemics reduction of need for ventilatory support and improved survival. have been well described.6 7 With SARS, OP http://bmjopenrespres.bmj.com/ and its histological variant, acute fibrinous and organising pneumonia (AFOP), were reported in 30%–60% of intensive care unit patients.7 INTRODUCTION The reported CT findings of COVID-19 suggest From the earliest reports of the novel virus that secondary OP, AFOP or both may be occur- SARS- CoV-2 causing a respiratory illness ring even more frequently.8–10 (COVID-19), clinicians remarked on the In this perspective, we review the clinical, © Author(s) (or their puzzling discordance between the degree radiographic, histopathological and treatment employer(s)) 2020. Re- use of hypoxemia and relatively modest work of response characteristics supporting the conclu- permitted under CC BY- NC. No breathing observed. Early reports described this commercial re- use. See rights sion that SARS- CoV-2–induced secondary on October 2, 2021 by guest. Protected and permissions. Published by combination as ‘silent hypoxemia’ and such OP, AFOP or both is the underlying cause of BMJ. patients as ‘happy hypoxemics’.1 2 Similarly, 1 COVID-19 respiratory disease in the majority of Advocate Aurora Critical Care soon after mechanical ventilation was instituted, patients. Service, Aurora St Luke’s unexpectedly high degrees of lung compli- Medical Center, Milwaukee, ance in conjunction with severe hypoxemia was Wisconsin, USA 2School of Medicine and deemed a new ‘L’ phenotype of acute hypox- CLINICAL PRESENTATIONS OF OP AND COVID-19 Public Health, University emic respiratory failure, attributed to an early OP has a unique clinical presentation gener- of Wisconsin–Madison, phase ‘dry lung’ with measured ‘hyperperfusion ally recognised by only experienced clini- Madison, Wisconsin, USA of gasless tissue’ as opposed to the significant cians.11 The widespread lack of familiarity with Correspondence to alveolar oedema and resulting hypoxic vasocon- the clinical presentation of OP may explain Dr Pierre Kory; striction observed in ‘traditional’ acute respira- the recent COVID-19 publication titles such 3 pierrekory@ icloud. com tory distress syndrome (ARDS). as “Is COVID-19 typical ARDS?”, “The mystery Kory P, Kanne JP. BMJ Open Resp Res 2020;7:e000724. doi:10.1136/bmjresp-2020-000724 1 BMJ Open Resp Res: first published as 10.1136/bmjresp-2020-000724 on 22 September 2020. Downloaded from Open access of the pandemic’s ‘happy hypoxia’” and “Why COVID-19 patients with OP, the radiographic and CT findings are often silent hypoxemia is baffling to physicians”, including a so characteristic that they suggest the pattern of injury.15 pro–con debate where COVID-19 was theorised similar to The ‘archetypal imaging findings’ refer to (1) peripheral, high- altitude pulmonary oedema.1 12 13 Although OP can bilateral, lower lung predominant consolidation or even present similarly to mild infectious pneumonia, inflamma- a frequent appearance in all lungs zones and/or (2) peri- tory markers such as C reactive protein are often markedly bronchovascular consolidation, which can extend to the elevated similar to COVID-19.11 subpleural regions in the lower lobes associated with patchy The descriptions of patients with COVID-19 presenting ground- glass opacities (GGO).15 The most compelling with ‘silent hypoxemia’ (low oxygen levels in the absence support for OP as the underlying pattern of lung injury from of respiratory distress) are strikingly similar to descriptions COVID-19 comes from an expert panel review, published in of OP where one report stated “hypoxemia with alveolar March 2020, which reported “the most common reported right- to- left shunt may be well tolerated”.11 Another descrip- CT findings in COVID-19 patients are typical of an organ- tion included “gas exchange abnormalities are extremely izing pneumonia pattern of lung injury”, with this pattern common with a reduction in the diffusing capacity of oxygen now described in virtually all published cases.8–10 Further, in and resting hypoxemia being almost universal findings” and a study of the diagnostic accuracy of CT among idiopathic “OP typically presents with mild dyspnea although occasion- interstitial pneumonias, the correct diagnosis of COP was ally it may be severe, especially in the event of rapidly progres- the highest, in 79% of cases, supporting that CT imaging sive disease, which more commonly occurs with AFOP”.11 14 features are characteristic and that “the typical imaging More specifically, one study assessed over 1100 pre- hospital features of COP are usually so characteristic that they allow 17 COVID-19 patients and found a significantly higher Sp02/ the possibility of diagnosis for most experienced clinicians”. respiratory rate ratio compared with pre- COVID-19 patients, Although variable radiographic findings in AFOP have substantiating far lower respiratory rates per degree of hypox- been described, patients who experience a rapidly progres- emia than is typical for other causes of acute hypoxemia. sive course exhibit imaging findings similar to diffuse alve- Thus, the clinical course of COVID-19 and secondary olar damage (DAD), with diffuse but basilar- predominant OP tend to follow a subacute respiratory illness, although consolidation and GGO.18 Those with a more subacute in both conditions a rapid- onset progression to fulminant course may have similar radiological findings of cryptogenic respiratory failure and even death from extensive fibrosis OP with focal or diffuse parenchymal abnormalities.18 has been described, with such cases reported to occur in copyright. approximately 5%–8% of secondary OP. Such fulminant cases may be contributing to the US mortality rate ranges reported among COVID-19–infected patients prior to the PATHOLOGICAL EVIDENCE FOR OP IN COVID-19 recent adoption of corticosteroid therapy.14–16 Although myriad agents and organisms are capable of injuring the lung, the histological responses to acute injury generally take three forms: DAD, OP or AFOP, and eosino- RADIOGRAPHIC EVIDENCE FOR OP IN COVID-19 philic pneumonia (EP), with EP not yet described in COVID- Both common and uncommon imaging patterns of OP have 15 19. In DAD, ‘diffuse’ refers to injury of both the alveolar and http://bmjopenrespres.bmj.com/ been described. However, in approximately 60%–90% of endothelial cell layers, thus causing fluid and proteins to leak into and accumulate in the alveolus. The two promi- nent phenotypes are the acute/exudative and organising/ proliferative, the former referring to the early phase where the leaked proteins form hyaline membranes that line the walls of the alveolus and cause non- resolution of the oedema
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