BMJ

Confidential: For Review Only Strengthening the Third Pillar: Primary Care and the UK COVID-19 Response

Journal: BMJ

Manuscript ID BMJ-2020-058797

Article Type: Analysis

BMJ Journal: BMJ

Date Submitted by the 23-May-2020 Author:

Complete List of Authors: Park, Sophie; UCL Medical School, Research Dept. of Primary Care and Population Health Elliott, Josephine; UCL Medical School Berlin, Anita; Queen Mary University of London, Institute of Health Science Education Haines, Andrew; London School of Hygiene & Tropical Medicine, Dept of Social and Environmental Health Research

Keywords: COVID-19, primary care, general practice

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1 2 3 1 Manuscripts are submitted online here: https://mc.manuscriptcentral.com/bmj 4 2 5 6 3 7 4 Analysis 8 5 9 10 6 Strengthening the Third Pillar: Primary Care and the UK COVID-19 11 7 Response 12 Confidential: For Review Only 13 8 14 9 Sophie Park1 15 10 Josephine Elliott 2 16 11 Anita Berlin 3 17 4 18 12 Andy Haines 19 13 20 14 1 Research Dept. of Primary Care and Population Health, UCL 21 15 2 UCL Medical School 22 16 3 Institute of Heath Science Education, Queen Mary University of London 23 4 24 17 Dept. of Public Health, Environments and Society and Dept. of Population Health, London 25 18 School of Hygiene and Tropical Medicine 26 19 27 20 Correspondence to: 28 21 Dr. Sophie Park 29 30 22 Research Department of Primary Care and Population Health 31 23 Royal Free Campus 32 24 Rowland Hill St. 33 25 Hampstead 34 26 London NW3 2PY 35 36 27 37 28 Email: [email protected] 38 29 Phone: 0207 794 0500 39 30 40 41 31 Word count: (Target: 1800-2000 words) 42 32 References: (up to 20 references, in Vancouver superscript style) 43 33 44 34 45 46 KEY MESSAGES 47 48  The emphasis in the UK COVID-19 response has been on public health and 49 hospital care, with the potential contribution of primary care largely 50 overlooked. Primary care strengths include provision of comprehensive 51 healthcare for individuals, continuity and gatekeeping. Planning which 52 includes and supports primary care can contribute to the COVID-19 53 response, increase resilience and minimise the impact of COVID-19 on other 54 healthcare needs. 55 56 57  Active engagement of primary care will be essential in management of the 58 second and subsequent waves of COVID-19, in order to improve care of 59 vulnerable patients in the community; reduce demands on hospital services; 60 support rehabilitation of recovering patients; improve palliative care; and

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1 2 3 4 sustain non-COVID 19 care. 5 6  Hospital admissions from COVID-19 require long and intensive treatment 7 with mortality often exceeding 30%. Potentially effective treatments 8 delivered early in the course of the disease in primary care settings should 9 be a priority for research funding. 10 11 ● Additional research and evaluation in primary care would inform the 12 Confidential:response to subsequent COVID-19 For waves, Review and strengthen Only the capacity of 13 primary healthcare to deal with the backlog of non-COVID-19 morbidity and 14 the medium-to-long term physical and mental health sequalae of COVID. 15 16 17 18 35 19 36 20 21 37 Contributors and sources 22 38 23 39 Sophie Park is a practising GP and clinical academic. She is Director of Medical Education 24 40 (Primary Care and Community) at UCL Medical School and Training Co-Lead for the NIHR 25 26 41 School of Primary Care Research (SPCR) Evidence Synthesis Working Group. Josephine 27 42 Elliott is a medical student and has an interest in public health and primary care, which 28 43 developed during her Masters in Medical Anthropology and internship at the WHO. Anita 29 44 Berlin is a GP and Professor of Primary Care Education at the Institute of Health Science 30 45 Education, Queen Mary University of London. Andy Haines is a Professor of Environmental 31 32 46 Change and Public Health at the London School of Hygiene and Tropical Medicine. He was 33 47 formerly a GP and Professor of Primary Health Care. All authors contributed to the 34 48 intellectual content contributed to drafting the text and approved the final draft. 35 49 36 50 37 51 Acknowledgements 38 52 Optionally include this section if you have any acknowledgements to make.N/A 39 40 53 41 54 42 55 Patient involvement 43 56 As The BMJ is seeking to advance partnership with patients, we also ask authors to seek 44 57 their input into articles wherever relevant, and document their involvement as patient 45 58 contributors or coauthors. In your statement, please specify how patients were involved and 46 59 how the article changed as a result of their contribution. If you did not seek input from 47 60 patients, please include a statement saying that no patients were involved. Ideally input from 48 61 patients will be sought at the article planning stage. 49 62 50 63 No patients were involved 51 64 52 65 53 66 Conflicts of Interest 54 67 We have read and understood BMJ policy on declaration of interests and have the following 55 68 interests to declare: 56 69 Note: where a competing interest exists that might disqualify an author from contributing, it is 57 70 wise to discuss it with a BMJ editor before writing the article. 58 71 We have no conflicts of interest 59 60 72

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1 2 3 73 4 74 Licence 5 75 The Corresponding Author has the right to grant on behalf of all authors and does grant on 6 76 behalf of all authors, an exclusive licence (or non exclusive for government employees) on a 7 77 worldwide basis to the BMJ Publishing Group Ltd ("BMJ"), and its Licensees to permit this 8 78 article (if accepted) to be published in The BMJ's editions and any other BMJ products and 9 10 79 to exploit all subsidiary rights, as set out in The BMJ's licence. 11 80 12 81 Confidential: For Review Only 13 82 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 83 Strengthening the Third Pillar: Primary Care and the UK COVID-19 4 5 84 Response 6 85 7 86 Standfirst 70 8 9 87 Most of the focus in addressing COVID-19 has been on public health and hospital-based 10 88 care. However, initial infection and many deaths occur in community settings with increasing 11 89 numbers of patients recovering from COVID-19 at home. COVID-19 clinical and research 12 90 strategiesConfidential: should capitalise on the strengths For of UK Review primary care including Only comprehensive 13 14 91 healthcare, continuity and gatekeeping, to build NHS resilience by capitalising on existing 15 92 primary care infrastructure and identifying effective, early interventions and follow-up 16 93 strategies. 17 94 18 95 19 96 The current COVID-19 response 20 21 97 This article examines current and future challenges and opportunities for primary care, and 22 23 98 highlights the urgent need for strategic planning and investment in primary care services, 24 99 evidence production and implementation. Globally, societies are attempting rapid 25 26 100 adjustments to direct and indirect consequences of life with COVID-19 1. Healthcare is at the 27 101 centre of these organisational changes, providing opportunities to draw on existing 28 29 102 strengths, and adapt systems to new challenges. Initial World Health Organisation (WHO) 30 31 103 recommendations were based on system adaptations in China, focusing predominantly on 32 104 secondary care (e.g. building new hospitals, initiating early ICU treatment) and public health 33 2 3 34 105 (e.g. early detection and institutional isolation) , . Despite the WHO’s commitment to 35 106 Universal Health Coverage and the universal access to primary care in the UK, primary care 36 37 107 has received less policy focus to date both globally and in the UK. 38 108 39 40 109 Internationally, primary care has experienced unprecedented shifts in work, with potential 41 4 42 110 short and longer-term changes of service organisation and patient outcomes . Systems 43 111 have varied in their capacity for rapid change; PPE availability; and use of volunteer support. 44 45 112 Taiwan, for example, report creating a tiered approach to primary care including walk-in 46 113 access, ‘prepared’ clinics for COVID-suspected cases, and screening 5. In Singapore, 47 48 114 existing primary care networks supported early detection and isolation 6. In anticipation of 49 50 115 subsequent peaks of COVID-19 and post-COVID morbidity, recognition that hospital case 51 116 fatality rates are over 30% (rising to 50% for those in ICU 7), and that hospitals are foci for 52 53 117 transmission, strategies are needed to refine management of patients at home and optimise 54 118 the use of NHS resources. ONS data show that many excess deaths are occurring outside 55 56 119 hospitals either from COVID-19, or from conditions for which care has been disrupted, 57 120 adding to the case for primary care response 8. 58 59 121 60

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1 2 3 122 4 5 123 6 124 Changes in UK Primary Care 7 8 125 UK general practice has undergone rapid changes over recent weeks. These are 9 10 126 underpinned by attempts to limit physical contact between patients and healthcare staff 11 127 requiring exponential increase in use of telemedicine to triage and address patient needs 12 Confidential: For Review Only 9 13 128 (e.g. telephone; video consultations , and e-consults). Triage aims to select patients for 14 129 face-to-face consultations (at the practice, patient’s home, or CCG co-ordinated ‘hot hubs’) 15 16 130 only where physical examination is anticipated to produce significant changes to 17 131 management, and the risks of contact outweigh potential benefits. 18 19 132 20 21 133 One major strategic decision at the outset of the UK COVID-19 epidemic was to utilise ‘111’ 22 134 rather than general practice infrastructure for patients with suspected infection. This was 23 24 135 understandable in the impending COVID-19 crisis, but meant that patients and healthcare 25 136 staff had to use 111 services (either directly or following GP recommendation) to access 26 27 137 testing (often commissioned to private providers) and secondary care support. When 111 28 138 services became over-whelmed, many GPs volunteered to support phone services. 29 30 139 31 32 140 While the use of 111 services shifted the immediate burden of patient COVID-19 diagnosis 33 141 and management, it also undermined the existing strengths of general practice to provide 34 35 142 contextualised (utilising knowledge of the patient’s co-existing conditions and home 36 143 situation) continuing and comprehensive care 10 . A clinician unfamiliar with a patient could 37 38 144 not, for example, utilise knowledge of the patient, their co-existing conditions and home 39 40 145 situation (e.g. history of domestic violence, deprivation) in decision-making. Similarly, it 41 146 focused efforts exclusively on COVID-19, rather than comprehensive attention to patients’ 42 43 147 mental health and co-morbidities. This reduction in continuity is likely to increase 44 148 unnecessary investigation and future demands on secondary care 11. It also reduces 45 46 149 opportunities for holistic discussion of home and palliative care management options with a 47 150 familiar healthcare professional. 48 49 151 50 51 152 Access to and navigation of fast-changing public health guidance and information about 52 153 newly adapted services have required additional levels of primary care support for many 53 54 154 patients, in some cases without access to smartphones, computers, printers and cars. GPs 55 155 are also co-ordinating and discussing with patients an influx of hospital ‘referral rejections’, 56 57 156 ‘COVID-related discharges’ and limited opportunities for secondary care (even for 58 59 157 assessment on fast track cancer pathways). Many patients in care homes are looked after 60 158 by GPs, who have often adapted approaches to minimise unnecessary contact using, for

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1 2 3 159 example, video ward rounds, electronic stethoscopes, oximeters and delegation to nursing 4 5 160 staff of death certification. For much of the time, support to care homes has been 6 161 inconsistent, compounded by inadequate PPE, with the Government support package only 7 8 162 published as recently as 15th May 12. 9 10 163 11 164 GPs have aimed, where possible, to support the families of patients cared for at home; in 12 Confidential: For Review Only 13 165 care homes; or in secondary care, including end-of-life care and resuscitation planning, and 14 166 provision of ‘just-in-case’ medications. This involves challenging navigation of physical 15 16 167 distancing and isolation requirements, minimising opportunities to visit admitted patients, 17 168 with probable long-term mental health sequalae for relatives. Ensuring optimal domiciliary 18 19 169 palliative care where needed, based on appreciation of the human dimensions of the 20 21 170 process and rituals of dying, requires careful support and planning, and where necessary, 22 171 coordination between primary and palliative care services 13. 23 24 172 25 173 Current Challenges 26 27 174 Many patients with COVID-19 are admitted to hospital with advanced disease and some 28 175 have died at home because deterioration can be sudden and relatively asymptomatic. This 29 30 176 can only be addressed by robust strategies to monitor patients at home, particularly those 31 32 177 with risk factors for poor outcomes, including the elderly and those with pre-existing 33 178 conditions, such as hypertension, diabetes, heart disease and stroke. Some patients who 34 35 179 are not candidates for intensive care because of advanced co-morbidities are sent to 36 180 hospital through 111 services, then discharged home to die, or die alone in hospital –when 37 38 181 involvement of primary care services would enable these patients to be better assessed and 39 40 182 cared for more humanely, with more family involvement. Overall, about 30% of registered 41 183 COVID-19 deaths occur outside hospitals, mainly in care homes and private residencies 8 42 43 184 with excess deaths above the seasonally adjusted average, contributing even more. 44 185 45 46 186 Current patterns of almost 100% virtual consultations cannot be maintained as COVID-19 47 187 moves into a long-term pattern with repeated infection peaks. While telemedicine is likely to 48 49 188 play a substantial role in the months ahead, it will be essential to plan, risk assess and 50 51 189 provide care for accumulating ‘backlogs’ of non-COVID acute and chronic disease 52 190 monitoring, assessment and referrals. It has become clear that ‘COVID-19 survivors’ 53 54 191 discharged into the community, may suffer from a range of early, chronic and severe mental 55 192 and physical sequelae – the natural history of which is still poorly understood. Lockdown 56 57 193 itself, may also exacerbate chronic mental, social and physical health problems. See figure 1 58 59 194 for examples of longer-term waves of impact from each peak. 60 195

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1 2 3 196 Figure 1: Four types of COVID-19 impact waves 4 197 (adapted with kind permission from Victor Tseng, Emory University). 5 6 198 COVID-19 has at least four types of impact wave. Each wave impacts at different time 7 199 points, potentially repeating for subsequent peaks, illustrated by the first wave of peak 2. 8 200 9 201 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 202 39 203 40 204 41 42 205 In the UK, the ‘voice of primary care’ has not yet been adequately represented in strategic 43 206 bodies (e.g. absence of primary care representation on the SAGE committee). 44 45 207 Communication has been unidirectional, predominantly downwards to primary care as 46 47 208 recipient, from public health and secondary care, rather than in partnership. The gap 48 209 between public health and primary care has been exposed by COVID-19. The location of 49 50 210 public health in local authorities has advantages for integration with local government 51 211 sectoral polices, but leaves primary care with patchy public health input and leads to the 52 53 212 fragmentation of responses that fail to address patients’ needs holistically. The importance of 54 213 primary-secondary care integration and communication has also become visible, especially 55 56 214 in light of fast-changing organisation of referral systems and processes. 57 58 215 59 216 Potential Responses 60

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1 2 3 217 4 5 218 Future primary care service design 6 219 Much can be learnt across international settings and response approaches. In the UK, a 7 8 220 systems approach is needed to develop an agile, coherent strategy to prepare the NHS for 9 10 221 subsequent COVID-19 peaks, rather than fragmented vertical programmes such as out- 11 222 sourced testing, contact tracing divorced from other services, and reliance on apps of 12 Confidential: For Review Only 14 13 223 unproven efficacy . This requires joint planning between primary and secondary care, 14 224 sharing knowledge and resources where possible, alongside integration of public health 15 16 225 expertise into CCGs and their Primary Care Networks (PCNs). This collaboration will support 17 226 development of education and training programmes, and strengthen resilient supply chains 18 19 227 for PPE; essential equipment; technologies for remote monitoring (e.g. p02, ECGs); and 20 21 228 opportunities for ‘bedside’ or same-day testing. 22 229 23 24 230 Primary care has been quick to utilise innovative virtual communication methods with 25 231 patients, but it is important to understand their limitations. Touch is an important aspect of 26 27 232 patient care 15 and while some conditions may be very suitable (where access allows) for 28 233 telemedicine consultations, others are less so because they require physical examination 16. 29 30 234 Careful assessment and follow up in primary care of patients recovering from COVID-19, 31 32 235 particularly from vulnerable groups, and their carers, will ensure access to rehabilitation 33 236 services and monitor respiratory, renal and other organ systems, as well as mental health. 34 35 237 Primary care will have a key role in delivery of serological testing for COVID-19 antibodies 36 238 and the scaling up of vaccination once effectiveness is assured. 37 38 239 39 40 240 Scaling up Primary Care Research 41 241 Rapid, but effective and relevant research needs to inform decision-making about the future 42 43 242 provision of primary care for patients. These studies can focus additional investment in 44 243 primary care, while also making visible gaps requiring innovation. It is critical, that this ‘crisis’ 45 46 244 is not used as an excuse for the rapid introduction of sustained and long-term change in 47 245 services and providers, without meaningful consultation with patient and professional 48 49 246 stakeholders, and in the absence of evaluative research. Many new technologies offer 50 51 247 promise but are as yet unevaluated. Evaluation of technologies to risk assess patients in the 52 248 community, such as wearable sensors to monitor vital signs and home testing for d-dimer, 53 54 249 the levels of which predict increased hospital mortality 17 should be funded without delay. 55 250 56 57 251 Experience of large scale Community Health Worker (CHW) programmes in low-income 58 59 252 settings is promising, including emerging evidence of their impact in COVID-19, but also 60 253 points to the need for PPE and adequate training. A rapid evidence review suggests CHWs

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1 2 3 254 have important roles in countering misinformation and stigma 18. CHWs also played 4 5 255 significant roles in controlling Ebola outbreaks in West Africa and DRC 19 20. Elsewhere, we 6 256 have argued that CHWs integrated with primary care could undertake a range of 7 8 257 assessment and monitoring roles in the UK 21. Evaluative research would be required 9 10 258 alongside the implementation of such programmes to ensure that they are having the 11 259 desired impact. 12 Confidential: For Review Only 13 260 14 261 Studies using large primary care databases linked to hospital data give the best prospect for 15 16 262 understanding prognostic factors and risk factors for acquiring the infection. They can also 17 263 detect potential candidates for drug trials and hazardous drugs by assessing death rates in 18 19 264 patients on medication. One example is the OpenSAFELY platform that pseudonymously 20 21 265 links primary care electronic health records managed by the electronic health record 22 266 company TPP, to patient-level data from the COVID-19 Patient Notification System (CPNS) 23 24 267 for death of hospital inpatients with confirmed COVID-19 22. 25 268 26 27 269 There is a need for trials of early intervention in COVID-19 to prevent deterioration and 28 270 reduce requirements for hospital admission. Antiviral treatments are more likely to be 29 30 271 effective in early disease and current trials in hospital settings may give an unrepresentative 31 32 272 view of their potential impact on outcomes. Other trials of early administration of agents to 33 273 prevent the cytokine storm and clotting disorders that appear to trigger sudden deterioration 34 35 274 and to provide early warning of such deterioration are needed. We conducted a search of all 36 275 COVID-related registered studies (Oxford and WHO databases – see figure 2): of 33 WHO 37 38 276 registered COVID-related UK studies, five were relevant to primary care. At the time of 39 40 277 writing, there is only one UK registered study of primary care COVID-19 treatment in the UK 41 278 23, the PRINCIPLE RCT of interventions (including medication) in older people and a number 42 43 279 of vaccine studies. 44 280 45 46 281 Figure 2: The setting of UK COVID-19 Studies 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 The setting of UK COVID-19 Trials 5 6 7 8 9 10 11 15% 12 Confidential: For Review Only 13 14 15 16 24% 61% 17 18 19 20 21 22 23 24 25 26 Number of COVID-19 trials in hospital/secondary/tertiary care 27 Number of COVID-19 trials in public health 28 Number of COVID-19 trials in primary care/general practice 29 282 30 283 31 32 Number of COVID-19 trials in hospital/secondary/tertiary care: 20 (61%) 33 Number of COVID-19 trials in public health: 8 (24%) 34 Number of COVID-19 trials in primary care/general practice: 5 (15%) 35 284 36 37 285 There have been increased GP registrations for the Oxford/RCGP Research Surveillance 38 24 39 286 Centre activities reporting suspected and confirmed COVID-19 cases ; COVID evidence 40 287 synthesis production 25; and COVID evidence mapping 26. But greater investment in primary 41 42 288 care research to examine medication and non-medication interventions that might prevent, 43 289 delay or treat COVID-19 is urgently needed. Similarly, although some existing trials are 44 45 290 adapting to explore COVID-19 impact within existing cohorts (e.g. multi-morbidity and 46 291 dementia), many more studies are needed to monitor and maximise effective treatment of 47 48 292 non-COVID conditions in the COVID-19 era. 49 50 293 51 294 Conclusion 52 53 295 Individual and organisational COVID-19 efforts have been rapid and extraordinary. They 54 296 have at times, however, been quite disparate and lacking connected, coherent strategy. The 55 56 297 principles of primary care (continuity; comprehensive and contextualised care; and 57 58 298 gatekeeping) and the potential for early intervention to reduce the risk of adverse outcomes 59 299 have a significant potential contribution to peri and post-COVID-19 clinical care and system 60

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1 2 3 300 resilience. This requires direct involvement in planning, adequate resource and support of 4 5 301 existing primary care infrastructure, alongside primary care evidence production and 6 302 implementation. 7 8 303 9 10 304 11 305 References 12 Confidential: For Review Only 306 13 14 307 1. Harris M, Bhatti,Y., Buckley, J., and Sharma, D. Fast and frugal innovations in response to 15 308 the COVID-19 pandemic. Nature Medicine 2020. 16 309 2. Dickens BL, Koo, J.R., Wilder-Smith, A., and Cook, A.R. Institutional, not home-based, 17 310 isolation could contain the COVID-19 outbreak. The Lancet 2020;395(10236):1541- 18 311 42. 19 312 3. Mission J. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID- 20 313 19). who.int: World Health Organisation 2020. 21 314 4. Marshall M, Howe, A., Howsam, G., Mulholland, M., and Leach, J. COVID-19: a danger 22 315 and an opportunity for the future of general practice. BJGP 2020 (in press). 23 316 5. Bih-Jeng Chang B, and Chiu, T.Y. Ready for a long fight against the COVID-19 outbreak: 24 317 an innovative model of tiered primary health care in Taiwan. BJGP Open 2020. 25 318 6. Lim WH, Wong, W.M. COVID-19: Notes from the Front Line, Singapore's Primary Health 26 319 Care Perspective. Annals of Family Medicine 2020;18(3). 27 320 7. Docherty AB, Harrison, E.M., Green, C.A., Hardwick, H., Pius, R., Norman, L., Holden, 28 321 K.A., Read, J.M., Dondelinger, F., Carson, G., Merson, L., Lee, J., Plotkin, D., Sigfrid, 29 322 L., Halpin, S., Jackson, C., Gamble, C., Horby, P.W., Nguyen-Van-Tam, J.S., 30 31 323 ISARIC4C, investigators, Dunning, J., Openshaw, P.J.M., Baillie, J.K., and Semple, 32 324 M.G. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC 33 325 WHO Clinical Characterisation Protocol. Medrxiv 2020. 34 326 8. ONS. Coronavirus (COVID-19): Latest data and analysis on coronavirus (COVID-19) in 35 327 the UK and its effect on the economy and society: Office for National Statistics 2020 36 328 [Available from: 37 329 https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditio 38 330 nsanddiseases 39 331 40 332 9. Greenhalgh T. Video Consultations: A Guide for Practice. http://BJGPlife.com: Royal 41 333 College of General Practice, 2020. 42 334 10. Park SA, R., Wong, G., Feder, G., Mahtani, K., Barber, J., and Salisbury, C. 43 335 Reorganisation of general practice: be careful what you wish for. BJGP 44 336 2019;69(687):517-18. 45 337 11. Pereira Gray DJ, Sidaway-Lee, K., White, E., Thorne, A., and Evans, P. . Continuity of 46 338 care with doctors - a matter of life and death? A systematic review of continuity of 47 339 care and mortality BMJ Open 2018;8(6). 48 340 12. Whately H. Coronavirus (COVID-19): support for care homes Department of Health and 49 50 341 Social Care2020 [Available from: 51 342 https://www.gov.uk/government/publications/coronavirus-covid-19-support-for-care- 52 343 homes. 53 344 13. Heath I. Matters of Life and Death: Key writings. Oxford: Radcliffe Publishing Ltd 2008. 54 345 14. Zastrow M. Coronavirus contact-tracing apps:can they slow the spread of COVID-19? . 55 346 Nature 2020. 56 347 15. Kelly M NL, McClurg C, Scherpbier A, King N, and Dornan T. Experience of touch in 57 348 healthcare: a meta-ethnography across the healthcare professions. Qualitative 58 349 Health Research 2018;2:200-12. 59 350 16. Wallace P, Haines, A., Harrison, R., Barber, J., Thompson, S., Jacklin, P., ROberts, J., 60 351 Lewis, L., and Wainwright, P. Joint teleconsultations (virtual outreach) versus

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1 2 3 352 standard outpatient appointments for patients referred by their general practitioner for 4 353 a specialist opinion: a randomised trail Lancet 2002;359:1961-68. 5 354 17. Zhang L, Yan, X., Fan, Q., Liu, H., Liu, X., Liu, Z., and Zhang, Z. D-Dimer Levels on 6 355 Admission to Predict In-Hospital Mortality in Patients with Covid-19 J Thromb 7 356 Haemost 2020. 8 357 18. Bhamik S, Moola, S., Tyagi, J., Nambiar, D., and Kakoti, M. Frontline health workers in 9 10 358 COVID-19 prevention and control: rapid evidence synthesis: The George Institute for 11 359 Global Health, India; 2020 [Available from: 12 360 https://cdn.georgeinstitute.org/sites/default/files/documents/frontline-health-workers-Confidential: For Review Only 13 361 covid-19-res_0.pdf 14 362 19. Knowx-Peebles C. Community health workers: the first line of defence against Covid-19 15 363 in Africa 2020 [Available from: https://www.bond.org.uk/news/2020/04/community- 16 364 health-workers-the-first-line-of-defence-against-covid-19-in-africa. 17 365 20. Miller NP, Milsom, P., Johnson, G., Bedford, J., Kapeu, A.S., Diallo, A.O., Hassen, K., 18 366 Rafique, N., Islam, K., Camara, R., Kandeh, J., Wesseh, C.S., Rasanathan, K., 19 367 Zambruni, J.P., and Papowitz, H. Community health workers during the Ebola 20 368 outbreak in Guinea, Liberia, and Sierra Leone. Journal of Global Health 2018;8(2). 21 369 21. Haines A, Falceto de Barros, E., Berlin, A., Heymann, D.L., and Harris, M.J. . National 22 370 UK programme of community health workers for COVID-19 response. The Lancet 23 371 2020;395(10231):1173-75. 24 372 22. Williamson E, Walker, A.J., Bhaskaran, K., Bacon, S., Bates, C., Morton, C., Curtis, H.J., 25 373 Mehrkar, A., Evans, D., Ingelsby, P., Cockburn, J., McDonald, H.I., MacKenna, B., 26 374 Tomlinson, L., Douglas, I.J., Rentsch, C.T., Mathur, R., Wong, A., Grieve, R., 27 375 Harrison, D., Forbes, H., Schultze, A., Croker, R., Parry, J., Hester, F., Harper, S., 28 376 Perera, R., Evans, S., Smeeth, L., and Goldacre, B. OpenSAFELY: factors 29 30 377 associated with COVID-19-related hospital death in the linked electronic health 31 378 records of 17 million adult NHS patients. medRxiv 2020. 32 379 23. Butler C, Ogburn, E., Allen, J., Bongard, E., Swayze, H., and Tonner, S. . A trial 33 380 evaluating treatments for suspected coronavirus infection in people aged 50 years 34 381 and above with pre-existing conditions and those aged 65 years and above 35 382 (PRINCIPLE) ISRCTN registry: BMC; 2020 [ISRCTN86534580]. Available from: 36 383 https://clinicaltrials.gov/ct2/show/NCT04303507. 37 384 24. RCGP. RCGP Research Surveillance Centre. Covid-19 Observatory 2020 [ 38 385 25. Heneghan C. Oxford COVID-19 Evidence Service Centre for Evidence-BAsed Medicine 39 386 2020 [Available from: https://www.cebm.net/oxford-covid-19-evidence-service/. 40 387 26. Thomas J. COVID-19: a living systematic map of the evidence eppi-centre, UCL: eppi- 41 388 centre, Institute of Education, UCL; 2020 [Available from: 42 389 http://eppi.ioe.ac.uk/cms/Default.aspx?tabid=3765. 43 390 44 391 45 46 392 Appendix: 47 393 48 Trial ID Scientific name of Trial: Expected Study Type: Setting Reason for allocation: number of allocation: 49 participants: 50 EUCTR2020- A randomised double-blind 200 UK Interventional Hospital Inclusion criteria list 51 001023-14- placebo-controlled trial to participants clinical trial of hospitalised and non- 52 GB determine the safety and (400 in the medicinal hospitalised COVID-19 efficacy of inhaled whole clinical product patients at Southampton 53 SNG001 (IFNß-1a for trial) General Hospital 54 nebulisation) for the 55 treatment of patients with confirmed SARS-CoV-2 56 infection (COVID-19) - 57 Phase II trial of inhaled 58 anti-viral (SNG001) for SARS-CoV-2 infection 59 NCT0431831 COVID-19: Healthcare 400 Observational Hospital 60 4 Worker Bioresource: [Patient  Inclusion criteria list

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1 2 3 Immune Protection and Registry] healthy asymptomatic 4 Pathogenesis in SARS- healthcare workers 5 CoV-2 attending hospital (place of work) 6 7 NCT0432638 Evaluation of Novel 200 Observational Hospital Inclusion criteria includes 8 7 Diagnostic Tests for 2019- patients requiring hospital 9 nCOV admission for symptoms suspicious of COVID-19 10 NCT0433340 Preventing Cardiac 3170 Interventional Hospital Inclusion criteria includes 11 7 Complication of COVID-19 patients with confirmed 12 Confidential:Disease With Early Acute For Review OnlyCOVID-19 infection who 13 Coronary Syndrome require hospital admission Therapy: A Randomised 14 Controlled Trial 15 ISRCTN14966 Does point-of-care testing 500 Hospital Inclusion criteria includes 16 673 for coronavirus in hospital that the participant must improve patient care Interventional be a hospital inpatient 17 compared to laboratory 18 testing? 19 NCT043371 Blood Titanium analysis of 100 Observational Hospital Inclusion criteria list 51 patients with MAGEC patients who have been 20 spine rod in the COVID-19 treated with, and still have, 21 environment a MAGEC rod, who are 22 (observational) based at the Royal 23 National Orthopaedic Hospital NHS Trust 24 NCT043455 Ayurveda Self- 18 Interventional Public Inclusion criteria list 25 49 Management for Flu Like Health participants with flu-like 26 Symptoms During the symptoms for less than 48 Covid-19 Outbreak hours 27 NCT043515 Ayurveda for Flu Like 32 Interventional Public Inclusion criteria list 28 42 Illness During Covid-19 Health participants with flu-like 29 Outbreak symptoms for less than 48 30 hours, who have been advised to self-isolate for 31 7-14 days 32 NCT043516 Development and 500 Observational Hospital Inclusion criteria list 33 46 Assessment of Rapid hospitalised patients and Testing for SARS-CoV-2 hospital NHS staff 34 Outbreak (DARTS) 35 NCT043525 COVID-19 and 1000 Observational Public This trial uses a 36 82 Vaccination Attitudes Health representative sample of 37 UK population for a survey to look at how vaccination 38 and other attitudes are 39 affected by COVID-19 40 CT0435475 AiM COVID for COVID-19 80 Observational Primary care Inclusion criteria list 3 tracking and prediction people who registered at, 41 or used, any community 42 support services in 43 Leicester 44 EUCTR2020 ChemoPROphyLaxIs For 1000 Interventional Hospital Inclusion criteria includes -001331-26- covId-19 infeCtious clinical trial of healthcare workers in 45 GB disease (the PROLIFIC medicinal hospitals accepting 46 trial) - PROLIFIC Trial product COVID-19 patients 47 (COVID-19) ISRCTN501 Randomized evaluation of 12000 Interventional Hospital Inclusion criteria list 48 89673 COVID-19 therapy hospital patients with 49 COVID-19 infection 50 ISRCTN400 Maternal and perinatal 500 Observational Hospital Inclusion criteria list 92247 outcomes of pandemic pregnant women admitted 51 COVID-19 in pregnancy to hospital with COVID-19 52 infection, aged 16-45 53 years old 54 ISRCTN512 Incidence and 70 Observational Hospital Inclusion criteria includes 87266 pathogenesis of invasive adults admitted to ICU for 55 aspergillosis in intensive >24 hours for suspected 56 care patients with severe COVID-19 infection 57 influenza or COVID-19 (AspiFlu) 58 ISRCTN169 In adult patients with 4002 Interventional Hospital Inclusion criteria includes 59 12075 known or suspected patients admitted to 60 COVID-19, does the use hospital with suspected or

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1 2 3 of Continuous Positive proven COVID-19 4 Airway Pressure (CPAP) 5 or high-flow nasal oxygen (HFNO), compared with 6 standard care reduce 7 mortality or need for 8 tracheal intubation? EUCTR2020 A phase I/II study to 510 Interventional Primary The inclusion criteria list 9 -001072-15- determine efficact, safety clinical trial of healthy adults (18-55yo) 10 GB and immunogenicity of the medicinal willing to have their 11 candidate Coronavirus product medical history discussed 12 Confidential:Disease (COVID-19) For Review Onlywith their GP and access vaccine ChAdOx1 nCoV- to their medical notes 13 19 in UK healhy adults 14 volunteers – a phase I/II 15 trial of a candidate COVID-19 vaccine 16 (COV001) 17 NCT043246 A Phase I/II study to 1090 Interventional Primary The inclusion criteria list 18 06 determine efficacy, safety healthy adults (18-55yo) and immunogenicity of the willing to have their 19 candidate Coronavirus medical history discussed 20 disease (COVID-19) with their GP and access 21 vaccines ChAdOx1 nCoV- to their medical notes 19 in UK healthy adult 22 volunteers 23 NCT043507 A phase 1, double-blind, 54 Public health Inclusion criteria list 24 36 randomised, placebo- Interventional medically healthy 25 controlled sponsor-open, volunteers for a phase 1 SAD and MAD study in study 26 health subjects to evaluate 27 the safety, tolerability, and 28 PK of inhaled TD-0903, a potential treatment for ALI 29 associated with COVID-19 30 NCT043545 The UK MS Register 3000 Observational Public health Inclusion criteria list adults 31 19 COVID-19 Substudy [Patient with confirmed multiple 32 Registry] sclerosis, enrolled on the UK MS Register 33 NCT043592 A Comparison of 3D and 80 Interventional Tertiary Inclusion criteria list pre- 34 25 2D Telemedicine: and post-op patient for 35 Communication During specific surgeries at a Covid 19 Regional Plastic Surgery 36 and Burns Unit 37 NCT030421 Repair of Acute 75 Interventional Hospital Inclusion criteria list 38 43 Respiratory Distress patients infected with Syndrome by Stromal Cell COVID-19 with moderate 39 Administration (REALIST): to severe ARDS, who are 40 An Open Label Dose receiving invasive 41 Escalation Phase 1 Trial mechanical ventilation 42 Followed by a Randomized, Double- 43 blind, Placebo-controlled 44 Phase 2 Trial (COVID-19) 45 NCT043598 Sequencing and tracking 500 Observational Hospital Inclusion criteria for 49 of phylogeny in COVID-19 generating this database 46 study of viral RNA sequences 47 includes that the 48 participant must have presented to Portsmouth 49 Hospital NHS Trust 50 NCT043596 A Single-site, 50 Interventional Hospital Inclusion criteria includes 51 54 Randomised, Controlled, patients hospitalised for 52 Parallel Design, Open- suspected COVID-19 label Investigation of an 53 Approved Nebulised 54 Recombinant Human 55 DNase Enzyme (Dornase Alfa) to Reduce 56 Hyperinflammation in 57 Hospitalised Participants 58 With COVID-19 59 NCT043661 An Observational Cohort 100 Observational Hospital Inclusion criteria includes 67 Study to Explore Patient patients undergoing 60 Outcome From Heart cardiac surgery during the

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1 2 3 Surgery During the Covid- COVID-19 pandemic 4 19 Pandemic 5 (CardiacCovid) ISRCTN439 Testing an early online 75 Interventional Public This is an online study for 6 00695 intervention for the Health adults who are affected by 7 treatment of disturbed either poor sleep or are 8 sleep during the COVID- good sleepers 19 pandemic (Sleep 9 COVID-19) 10 ISRCTN865 Platform Randomised trial 3000 Interventional Primary This trial studies COVID- 11 34580 of INtervention against 19 symptoms in the 12 Confidential:COVID-19 in older people For Review Onlycommunity with the trial (PRINCIPLE) centre being all 13 participating GP practices 14 in England 15 NCT040613 Serum testing of 3500 Observational Primary This trial involves use of 82 representative youngsters: General Practice 16 sero-epidemiological vaccination records 17 survey of England in 18 2019/2020 EUCTR2020 A pilot, open label, phase 24 Interventional Hospital Inclusion criteria list ICU or 19 -001640-26- II clinical trial of nebulised clinical trial of ward-based patients with 20 GB recombinant tissue- medicinal confirmed infection with 21 Plasminogen Activator product COVID-19 22 (rtPA)in patients with COVID-19 ARDS: The 23 Plasminogen Activator 24 COVID-19 ARDS (PACA) 25 trial NCT043568 A Pilot, Open Label, 24 Interventional Hospital Inclusion criteria list 26 33 Phase II Clinical Trial of hospital in-patients with 27 Nebulised Recombinant confirmed infection with 28 Tissue-Plasminogen COVID-19 29 Activator (Rt-PA) NCT043630 Immune cells and the 125 Observational Public Inclusion criteria list those 30 47 Coronavirus for Health who have previously taken 31 inflammatory arthritis part in BRAGGSS or the 32 National Repository health Volunteer Study 33 NCT043698 Mapping organ health 507 Observational Public health This is a prospective, 34 07 following COID-19 disease longitudinal observational 35 due to SAR-CoV-2 cohort study of patients 36 infection recovering from COVID-19 CTRI/2020/0 Viral Infection and 5000, but this Observational Hospital Inclusion criteria includes 37 4/024473 Respiratory illness includes hospital patients with a 38 Universal Study recruitment high clinical suspicion of, non-UK 39 or confirmed, COVID-19 countries infection 40 394 41 42 395 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Figure 1 (currently also embedded in the text) 32 33 361x270mm (72 x 72 DPI) 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 17 of 17 BMJ

1 2 3 4 5 Confidential: For Review Only 6 7 The setting of UK COVID-19 Trials Number of COVID-19 trials in hospital/secondary/tertiary care 20 (61%) 8 Number of COVID-19 trials in public health 8 (24%) 9 Number of COVID-19 trials in primary care/general practice 5 (15%) 10 11 12 13 14 15% 15 16 17 18 24% 19 61% 20 21 22 23 24 25 26 27 28 Number of COVID-19 trials in hospital/secondary/tertiary care 29 30 Number of COVID-19 trials in public health 31 Number of COVID-19 trials in primary care/general practice 32 33 34 35 36 37 38 39 https://mc.manuscriptcentral.com/bmj 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60