key: cord-0755634-gewokwgu authors: kalin, A.; Greenhalgh, T.; Javid, B.; Knight, M.; Inada-Kim, M. title: What is the efficacy and safety of rapid exercise tests for exertional desaturation in Covid-19: A rapid review protocol date: 2020-11-04 journal: nan DOI: 10.1101/2020.10.31.20223453 sha: 6c68d541e3e2467d940b329a0f0b819b9f7e411f doc_id: 755634 cord_uid: gewokwgu Background Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We sought to summarise the literature on the performance of different rapid tests for exertional desaturation. Research question What tests have been formally evaluated for the rapid assessment of exertional hypoxia? What is the evidence for their accuracy, practicability and safety in the context of suspected acute Covid-19? To what extent will these tests help identify patients with evidence of either silent or hidden hypoxia leading to earlier recognition of those at risk of severe outcomes? Method We aim to review three independent searches of AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases until 24th September 2020. Screening, data abstraction, and quality appraisal of full-text papers will be completed independently by two reviewers including a topic expert and a review expert. Studies will be tabulated and assessed for risk of bias using QUADAS 2 tool. We aim to review three independent searches of AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases until 24 th September 2020. Screening, data abstraction, and quality appraisal of full-text papers will be completed independently by two reviewers including a topic expert and a review expert. Studies will be tabulated and assessed for risk of bias using QUADAS 2 tool. This rapid review aims to produce key findings relevant to the assessment of exertional desaturation in patients with suspected Covid-19. Establishing a validated tool to assess exertional desaturation will help to ensure that future research on this topic can be undertaken in a consistent way. An exertional desaturation test should be used in combination with a comprehensive clinical evaluation and only on patients whose resting oximetry reading is 96% or above unless in a supervised care setting. It should be terminated if the patient experiences adverse effects. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. [1] . The degree of lung involvement in acute Covid-19 is variable, producing a spectrum of illness from mild upper respiratory tract symptoms to acute respiratory distress syndrome [2] . Patients with mild initial symptoms can rapidly deteriorate to severe or critical cases. In hospitalised patients, hypoxaemia and the need for oxygen are independent predictors of severe outcomes [3, 4] . The usual time from symptom onset to the development of severe hypoxemia is between 7 and 12 days [5, 6] . Recent prognostic tools such as the 4C score have emphasised the importance of identifying hypoxia early [3, 7] and there are physiological reasons for managing this hypoxia actively [8, 9] . The poor correlation between both subjective feeling of shortness of breath (dyspnoea) and objective measures of breathlessness and hypoxia in patients with Covid-19 has resulted in UK guidelines recommending that the assessment of the breathless, unwell or high-risk patient should include oximetry [5] . For example, a retrospective cohort study of 64 Covid-19 patients considered eligible for home oximetry monitoring showed that the presence of dyspnoea had a positive predictive value of only 42% for hypoxemia and absence of dyspnoea had a negative predictive value of 86% for excluding it [10] . Indeed, the mismatch between relatively mild subjective respiratory distress and objective evidence of peripheral hypoxia is now recognised as a feature of Covid-19 and has been termed "silent" or "happy" hypoxemia [11, 12] . This mismatch has been attributed to moderate to severe ventilation-perfusion mismatch [11] . Whereas many common lung diseases (such as asthma and chronic obstructive pulmonary disease) produce mainly ventilation defects where air does not reach the alveoli, some (such as interstitial lung disease, sarcoidosis and pulmonary embolism) produce defects of perfusion in which gas transfer across the alveolar-capillary barrier is impaired. Several mechanisms for the perfusion defect in Covid-19, including intra-pulmonary shunting, loss of lung perfusion regulation, intravascular microthrombi or reduced lung compliance, have been proposed [12, 13] . [2] . They suggest that the 6MWT or 3MWT test can be performed at home or in hospital under the supervision of either a family member or a healthcare professional. These authors define exertional hypoxia All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 4, 2020. as an absolute drop in oximeter reading by 3% or more from baseline, and recommend escalation of care for all such patients. In sum, consensus guidance and editorials recommend tests for exertional hypoxia in Covid-19, but the evidence base for these tests has not previously been formally reviewed. Indeed, the prognostic utility of exertional desaturation remains unknown. Another unknown is the safety of such tests in patients with suspected Covid-19, especially when used remotely without a clinician physically present. Establishing a validated tool to assess exertional desaturation will help to ensure that future research on this topic can be undertaken in a consistent way. The overall objective of this rapid review is to examine the published evidence base for the use of rapid exercise tests to confirm or exclude exertional hypoxia in patients with Covid-19. We are particularly interested in tests that could be used outside of the clinical setting, since the reality of acute Covid-19 often involves a remote assessment (with the patient at home at a distance from the clinician) or one in a bespoke ambulatory setting such as a "hot hub" (where exercise tests may be performed outside in car parks, for example, for infection control reasons). The research questions are: We are going to follow Cochrane Rapid Review guidelines [22] . Our team includs experienced health librarians as well as systematic reviewers and clinicians (including a All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Three independent searches will be conducted. The first will search LitCovid, Scholar and Google using the terms 'step test or field test' and 'hypoxia or exertional desaturation'. From these results, promising articles will then be used to find additional documents via two methods -forward and backward citation matching, and searching for related articles (also using Microsoft Academic Search). The second search will covered the following databases: AMED, CINAHL, EMBASE MEDLINE, and PubMed using the over-arching question 'Very short exercise desaturation tests for use in the emergency department'. Search terms are: (quick OR short) AND oxygen) AND exercise) AND (desaturation OR saturation)) AND test*("emergency department*" AND oxygen) AND exercise) AND desaturation) AND test*) ("emergency department*" AND oxygen) AND exercise) AND saturation) AND test*) ("emergency department*" AND oxygen) AND exercise) AND desaturation) ("emergency department*" AND oxygen) AND exercise) AND saturation) (1-min sit-to-stand test) or ("1 min sit to stand test") or ("one-minute sit to stand") The third search will involve searching the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane COVID-19 study register. Search strings for different searches are listed below. Search of Cochrane Library -Issue 10 of 12, October 2020: All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020.10.31.20223453 doi: medRxiv preprint #1 (("step test" OR "walk test" OR "field test" OR "chair rise" OR "sit to stand" OR "exercise test" OR "exercise testing")):ti,ab,kw OR (exertional NEAR/2 (desaturation OR hypoxia)):ti,ab,kw Search of Cochrane COVID-19 study register: "step test" OR "walk test" OR "field test" OR "chair rise" OR "sit to stand" OR "exercise test" OR "exercise testing" Our inclusion criteria used the PICOS/T frameworks as follows: Population: Individuals with Covid-19 or another lung disease with or without symptoms. Interventions: Any form of rapid exercise test performed at home or in a healthcare setting. Comparator: 6MWT or cardiopulmonary exercise test, CPET (both of which are used as gold standard in exercise testing), or a diagnostic test to diagnose the disease in question (eg bronchoalveolar lavage to diagnose pneumocystis carinii pneumonia). Outcome. Pulse oximetry or arterial blood gas measurement, and association with any adverse outcome e.g. hospital admission, need for organ support, death. Time periods: All periods of time and duration of follow up. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 4, 2020. ; https://doi.org/10.1101/2020. 10.31.20223453 doi: medRxiv preprint No other limitations are imposed on the search or study selection process. Both peerreviewed and preprint papers will potentially be eligible for inclusion. We plan to seek translation of any relevant papers published in languages other than English. The risk of bias in individual studies will be assessed using the QUADAS 2 tool. Using the signalling questions, we will rate each potential source of bias as high, low, or unclear. [23] . Tests involving climbing a flight of stairs should be avoided, since a staircase is a dangerous place to collapse. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. The Lancet Infectious Diseases Unmasking Hypoxia in COVID 19 -Six Minute Walk Test Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score Association between hypoxemia and mortality in patients with COVID-19 COVID-19 rapid guideline: managing suspected or confirmed pneumonia in adults in the community. London: NICE; 2020. Accessed 30th Proposed Modifications in the 6-Minute Walk Test for Potential Application in Patients With Mild COVID-19: A Step to Optimize Triage Guidelines Development and validation of the 4C Deterioration model for adults hospitalised with COVID-19 Considerations for target oxygen saturation in COVID-19 patients: are we under-shooting? BTS guideline for oxygen use in adults in healthcare and emergency settings The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19 The pathophysiology of 'happy'hypoxemia in COVID-19 The mystery of the pandemic's 'happy hypoxia Basing respiratory management of COVID-19 on physiological principles Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area Clinical characteristics of coronavirus disease 2019 in China Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries Pulse oximetry to detect early deterioration of patients with COVID-19 in primary and community care settings. London: NHSE/I. Accessed 17th Reference guide for emergency medicine. London: NHS England. Accessed 17th Principles of safe video consulting in general practice during COVID-19 Remote Covid-19 Assessment in Primary Care (RECAP) early warning score: item development Besides other Signs, Can a 6-min Walk Test be Applied as a Criterion for Going to the Hospital with a Diagnosis of COVID-19? Cochrane Rapid Reviews. Interim Guidance from the Cochrane Rapid Reviews Methods Group Exercise testing in the prognostic evaluation of patients with lung and heart diseases