Cohort Profile: Post-Hospitalisation COVID-19 (PHOSP-COVID) study

The Post-Hospitalisation COVID-19 (PHOSP-COVID) study is a national UK multicentre cohort study of patients who were hospitalized for COVID-19 and subsequently discharged. PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalization, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments and to serve as a platform to enable future studies, including clinical trials. Data collected covered a wide range of physical measures, biological samples and patient-reported outcome measures (PROMs). Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA; or in Tier 2 in which they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at 5 (range 2–7) months and 12 (range 10–14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites. All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research. In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022. Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals from https://www.phosp.org/data-sample-request/. To date, there have been >750 million reported cases of COVID-19 globally since the pandemic began in early 2020.1 In the UK, there have been >1 million patients hospitalized and 180 000 deaths due to COVID-19.2 Previous viral epidemics and conditions causing acute respiratory distress syndrome caused long-lasting health impacts on the affected survivors.3,4 At the time of conception of the Post-Hospitalisation COVID-19 (PHOSP-COVID) cohort in March 2020, the longer-term pulmonary and multisystem effects of COVID-19 and impact on health status were unknown.5 We identified a need to establish a cohort of hospitalized COVID-19 survivors to collect detailed information about the medium- and long-term effects of COVID-19 on physical and mental health, lifestyle and occupation status. Although the majority of individuals with COVID-19 were not hospitalized, we expected that the consequences of COVID-19 might be most pronounced after severe illness. Furthermore, the pressures on health systems during the pandemic needed to be taken into consideration when establishing a new clinical cohort. Therefore, we designed the PHOSP-COVID study to align with clinical follow-up reviews of hospitalized patients, where possible. PHOSP-COVID was designed to take a patient-centred, holistic approach to understanding the medium- and long-term effects of COVID-19, recognizing the need to consider physical and mental health, social support and lifestyle. There were three main aims of PHOSP-COVID: To determine the medium- and long-term health (and health economic) sequelae of COVID-19 in post-hospitalization survivors; to define demographic, clinical and molecular biomarkers of susceptibility, including to severity of the acute illness and development, progression and resolution of sequelae. To understand the impact of inpatient and post-discharge, pharmacological and non-pharmacological interventions on long-term sequelae of COVID-19. To build the foundation for in-depth studies of emergent conditions and worsening of pre-morbid disease to inform precision medicine in at-risk groups by directing new clinical trials and care for current and future patients with long COVID. Individuals who were discharged from hospital between 1 February 2020 and 31 March 2021 were invited to participate in the PHOSP-COVID study if they were: aged ≥18 years, admitted to a participating UK hospital with confirmed or clinically suspected COVID-19 and able to provide informed consent either personally or via a consultee or an appropriate representative. Exclusion criteria included: admission due to a diagnosis of a different pathogen with no indication or likelihood of co-infection with COVID-19, attendance at emergency department only, declined to provide informed consent or life-limiting illness with life expectancy of <6 months such as disseminated malignancy. During the recruitment period (August 2020 to March 2022), eligible patients were invited to participate in the study by research teams based at the participating sites ≤1 year after discharge. A total of 83 sites from England, Northern Ireland, Scotland and Wales participated following the study advertisement in social media and research networks. Different methods were used to obtain consent including: face-to-face, telephone, postal and eConsent. Participants could join as Tier 1 participants only with remote data collection or could join as Tier 2 participants in which they were invited to attend two research visits for further data collection and biological research sampling (Figure 1). Consort diagram of the Post-Hospitalisation COVID-19 (PHOSP-COVID) study. aThe wide range window for the first research visit (2–7 months) was deliberately chosen to accommodate the variation in planned clinical follow-up appointments across the different participating sites and to allow the research visit to coincide with the planned clinical follow-up appointments Participants in either Tier 1 or Tier 2 could additionally join Tier 3 sub-studies in which they were either recalled for additional research procedures or undertook additional research procedures during their Tier 2 research visits. For example, a subset of 141 participants had an extended blood draw to enable additional sampling and advanced cellular studies6 and another subset of 531 participants completed up to three whole-body magnetic resonance imaging (MRI) scans to examine the effect of COVID-19 on multiple body organs (Capturing MultiORgan Effects of COVID-19, C-MORE sub-study).7,8 A total of 7935 participants were recruited into the PHOSP-COVID cohort—5238 participants to Tier 1 and 2697 to Tier 2—between 10 August 2020 and 31 March 2022. The participants’ demographics, comorbidities and admission characteristics are detailed in Table 1 and Supplementary Table S1 (available as Supplementary data at IJE online). Over 1000 participants to date have also been included in Tier 3 studies. Participant demographics, comorbidities and admission characteristics of the Post-Hospitalisation COVID-19 (PHOSP-COVID) cohort Data are n (%) unless indicated. Percentages are calculated by category after exclusion of missing data for that variable. Mean (SD). Median [IQR]. WHO classes are: 3–4 = no continuous supplemental oxygen needed; 5 = continuous supplemental oxygen only; 6 = continuous or bi-level positive airway pressure ventilation or high-flow nasal oxygen; and 7–9 = invasive mechanical ventilation or other organ support. See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. IQR, interquartile range; SARS-CoV-2 PCR, severe acute respiratory syndrome coronavirus 2 polymerase chain reaction; WHO, World Health Organization. Participant demographics, comorbidities and admission characteristics of the Post-Hospitalisation COVID-19 (PHOSP-COVID) cohort Data are n (%) unless indicated. Percentages are calculated by category after exclusion of missing data for that variable. Mean (SD). Median [IQR]. WHO classes are: 3–4 = no continuous supplemental oxygen needed; 5 = continuous supplemental oxygen only; 6 = continuous or bi-level positive airway pressure ventilation or high-flow nasal oxygen; and 7–9 = invasive mechanical ventilation or other organ support. See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. IQR, interquartile range; SARS-CoV-2 PCR, severe acute respiratory syndrome coronavirus 2 polymerase chain reaction; WHO, World Health Organization. Overall, the cohort has a mean age of 59.3 years, 40% of participants are female, 82% report White ethnicity and 23% are from the lowest quintile of the Index of Multiple Deprivation. The cohort was comorbid, with >55% of participants having two or more pre-existing comorbidities at the time of hospital admission. More than 93% had a positive SARS-CoV-2 RT-PCR test result on admission and 38% required non-invasive or invasive ventilation (Class 6 or above on the World Health Organization clinical progression scale)9 during their original hospital admission. Given the pressures of the ongoing pandemic during recruitment, non-response to invitations to join the study was not recorded. Data collection for Tier 1 participants was restricted to available clinical data from routine hospital follow-up plus the collection of patient-reported outcome measures (PROMs) via an app every 3 months for ≤1 year post discharge. Tier 2 participants were invited to two research visits: the first between 2 and 7 months, and the second between 10 and 14 months post hospital discharge. Of the 2570 Tier 2 participants who attended the first research visit (labelled as the 5-month visit due to the median length of time between discharge and the visit), 1973 participants also attended a second research visit (labelled the 1-year visit). A further 127 Tier 2 participants attended the 1-year visit only (Figure 1). The characteristics of the 597 participants who did not return for a 1-year visit are listed in Supplementary Table S2 (available as Supplementary data at IJE online). All participants provided consent for further data collection via linkage to retrospective and prospective healthcare and social-care records including primary care, hospital episode statistics and specialist tertiary clinical databases for ≤25 years. Participants were also invited to provide consent to be re-contacted for further research, including Tier 3 sub-studies, such as mechanistic studies and clinical trials.10 A summary of the data collected for PHOSP-COVID participants is provided in Table 2. For all participants, information about their demographics, acute illness and hospital admission were obtained retrospectively from hospital notes by the research team once a consent form was signed. This included: comorbidities, presenting symptoms, length of stay, severity of acute illness, treatment received, complications and common clinical test results. Hospital records were also reviewed to collect clinical data obtained from any planned follow-up appointments organized by the local hospital team after discharge. These included: physiological tests and imaging, routine blood test results and clinical questionnaires (Supplementary Table SM1, available as Supplementary data at IJE online). Further data were collected on post-discharge care accessed including mental health interventions, rehabilitation programmes and details from any emergency hospital admission for ≤1 year post discharge. All the captured data measures were recorded on paper forms then transferred to a study-specific online database and subsequently to a national Data Safe Haven. The Post-Hospitalisation COVID-19 (PHOSP-COVID) outcome measures Pittsburgh Sleep Quality Index (PSQI) Morningness-Eveningness Questionnaire (MEQ) Pittsburgh Sleep Quality Index (PSQI) Morningness-Eveningness Questionnaire (MEQ) The results of these outcomes measures were only available for collection if performed for clinical indications by the local medical team. A subset of Tier 1 participants remotely completed health-related questionnaires using an electronic app. 6MWT, 6-min walk test; BNP, brain natriuretic peptide; CPET, cardiopulmonary exercise testing; CRP, C-reactive protein; CT, computed tomography; DNA, deoxyribonucleic acid; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; FBC, full blood count; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume measured in 1 s; FVC, forced vital capacity; HbA1C, glycated haemoglobin; INR, international normalized ratio; KCO, carbon monoxide transfer coefficient; LFTs, liver function tests; MRC, Medical Research Council; MRI, magnetic resonance imaging; NT-BNP, N-terminal BNP; PBMCs, peripheral blood mononuclear cells; PCR, polymerase chain reaction; RNA, ribonucleic acid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TLCO, transfer capacity of the lung for carbon monoxide; U&Es, urea, creatinine and electrolytes. The Post-Hospitalisation COVID-19 (PHOSP-COVID) outcome measures Pittsburgh Sleep Quality Index (PSQI) Morningness-Eveningness Questionnaire (MEQ) Pittsburgh Sleep Quality Index (PSQI) Morningness-Eveningness Questionnaire (MEQ) The results of these outcomes measures were only available for collection if performed for clinical indications by the local medical team. A subset of Tier 1 participants remotely completed health-related questionnaires using an electronic app. 6MWT, 6-min walk test; BNP, brain natriuretic peptide; CPET, cardiopulmonary exercise testing; CRP, C-reactive protein; CT, computed tomography; DNA, deoxyribonucleic acid; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; FBC, full blood count; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume measured in 1 s; FVC, forced vital capacity; HbA1C, glycated haemoglobin; INR, international normalized ratio; KCO, carbon monoxide transfer coefficient; LFTs, liver function tests; MRC, Medical Research Council; MRI, magnetic resonance imaging; NT-BNP, N-terminal BNP; PBMCs, peripheral blood mononuclear cells; PCR, polymerase chain reaction; RNA, ribonucleic acid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TLCO, transfer capacity of the lung for carbon monoxide; U&Es, urea, creatinine and electrolytes. For participants in Tier 1, clinical data were obtained from medical records and no specific research visit was undertaken. However, a subset of Tier 1 participants used an online app to remotely questionnaires and a study-specific Questionnaire The was used to collect information about ongoing symptoms, in occupation and where the was asked to or to the from A total of participants provided using the online PROMs app Tier 1 and Tier between 2021 and 2022. subset of Tier 1 participants provided a saliva sample for via a collection to their (Supplementary Table available as Supplementary data at IJE online). At Tier 2 research clinical procedures and sampling were including of the was using questionnaires and physical tests including: and and All Tier 2 participants were additionally invited to physical using a for 14 function was using and of transfer when the COVID-19 on procedures outcome measures, and physiological and tests Tier 2 participants by the research visits Data are n (%) unless indicated. data not included in Mean (SD). Median [IQR]. of or for of See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. of BNP, brain natriuretic peptide; clinical CRP, C-reactive protein; and eGFR, estimated glomerular filtration rate; of FEV1, forced expiratory volume measured in 1 s; FVC, forced vital capacity; HbA1C, glycated haemoglobin; walk test; KCO, carbon monoxide transfer coefficient; of NT-BNP, N-terminal BNP; Health patient-reported outcome physical TLCO, transfer capacity of the lung for carbon outcome measures, and physiological and tests Tier 2 participants by the research visits Data are n (%) unless indicated. data not included in Mean (SD). Median [IQR]. of or for of See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. of BNP, brain natriuretic peptide; clinical CRP, C-reactive protein; and eGFR, estimated glomerular filtration rate; of FEV1, forced expiratory volume measured in 1 s; FVC, forced vital capacity; HbA1C, glycated haemoglobin; walk test; KCO, carbon monoxide transfer coefficient; of NT-BNP, N-terminal BNP; Health patient-reported outcome physical TLCO, transfer capacity of the lung for carbon All were performed as of the two research visits when measures were available from clinical follow-up appointments at the time to procedures and All Tier 2 participants were invited to provide and samples for research different were and (Supplementary Table available as Supplementary data at IJE online). All samples were at the local at for longer-term at a central This of samples their in studies. Participants were asked to consent to of their samples by other including in the UK and Participants were an to their consent for studies. The participants’ consent to healthcare records to and of clinically including and scans from participating which were transferred to a national imaging database COVID-19 for and (Supplementary Table available as Supplementary data at IJE online). for Tier 3 sub-studies were on the specific criteria of the whole-body imaging scans as of the C-MORE (Supplementary Table available as Supplementary data at IJE body using imaging or further using the online test In to that the was central to the research using the PHOSP-COVID a and exercise was between 2020 and March 2021 to determine 10 research The from with long clinical and including the and A of the was A total of were to and into a of that was an online The 10 research were at a by and via The 10 research are listed in Supplementary Table (available as Supplementary data at IJE online). from the first Tier 2 participants at 5 months post discharge that only of participants reported a new as by using the on and were no The 10 were: physical or and a in These were with reported from or of patients with a severe in of the cohort had clinically of and and of the participants had of measured using the and at 5 months post discharge. There was also of specific organ had or had lung had at had function and had brain natriuretic Further of lung using clinical imaging at a median of months post discharge of the lung were in of a subset of PHOSP-COVID The of lung was estimated to be between and and a clinically that of the cohort had to of lung post A was the of a between the severity of the acute illness and the ongoing symptoms, mental and physical health with the of pulmonary function tests and which were in the who invasive mechanical At 1 year after hospital there was from 5 months in ongoing symptoms, mental health, physical and and organs The 10 most were also to at 5 and were in more than of participants at 1 A in the of participants at 1 year was with of who were no and of participants that COVID-19 had in a in their occupation (Supplementary Table available as Supplementary data at IJE online). from the Tier 2 cohort for the early and 1-year research visits are included in 3 and of life and Tier 2 participants by the research visits Data are n (%) unless indicated. data not included in Mean (SD). Median [IQR]. See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. of of life and Tier 2 participants by the research visits Data are n (%) unless indicated. data not included in Mean (SD). Median [IQR]. See Supplementary Table SM1 (available as Supplementary data at IJE online) for further descriptions of variables. of The with of at 1 year were: female, and having invasive mechanical ventilation or other organ support during the acute of treatment with acute during the acute admission was not with any effect on at 1 year the acute was also with and health-related of life at 1 year following We identified for new or post at 5 months, including pre-existing and hospital Further has also in of the with and an We undertook using measures of physical and at 5 months and The severity of most of the health in the and the was by (Figure The more severe were with body a of symptoms, physical function and C-reactive The was with continuous of physical total time and in Although these are for which of effect have not been these data of the of and physical health with The the of the and the of identified that were with the after rate; 2; 3 2; To investigate the of were measured at 5 including were in the and the with with the (Figure These of and provide biological mechanisms the and health with severe long The of clinical with the biological research PHOSP-COVID of the of hospitalized COVID-19 survivors in the and are measured in Tier 2 These underlying mechanistic in and inform trials. We have participants in PHOSP-COVID to the and study where This additional information and linkage to samples taken during acute hospital admission. We are to other including viral data and electronic healthcare records, The results by the PHOSP-COVID cohort are to and of clinical care at when the national health and are pressure after the research and groups the of clinical and at the volume of patients with long The study was designed as a with the study as COVID-19 hospitalized survivors with a range of outcomes captured nested no groups COVID-19 individuals hospitalized with other viral were recruited to the study. However, has been by using or to examine participants were recruited following discharge from data to health status were only available from healthcare records or by the for There is also as of the participants might have the to the study due to the severity of their ongoing This is to Tier 2 participants, who were more and required more respiratory support with the participants included in the which are more of the hospitalized in the However, the linkage to and other databases to and the PHOSP-COVID cohort included participants from 83 different sites and due to the pressure with clinical and during the of the there were in the of collected data across these multiple sites. However, the of recruited participants the PHOSP-COVID of the multicentre recruitment began in August 2020, the cohort patients who were admitted to hospital during the first year of the pandemic and the of the and and the wide of acute In as in the UK did not 2020, a of the cohort were at hospital admission and at the 5-month The PHOSP-COVID study an of the information about and Research using the study is organized across a of groups (Figure These were established at the of the study to research, of and across research and clinical in research using PHOSP-COVID are to the in the first The data are held in the Data to these data are to for information and to be to A the of PHOSP-COVID at approach to the clinical care and with the different groups of the Post-Hospitalisation COVID-19 (PHOSP-COVID) and A A A A A A A and from the and A A A A A A A A A A A A A A A A A A A A A A A A A in A A A A A A A A A A A A A A A A A A A A A A A A A A A White A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A UK and A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A The study was by the Research and is on the See of the Supplementary data are available at IJE The was by and and further by the and to the conception and of the and to the of All to data and of the and have accessed and the underlying and were for the to the and are for all of the in that to the or of any of the are and This was by a from the UK Research and and of Health Research and The in the are of the and not of the Health the or the of Health and The research was in by the This study not be all the participants who have their time and support. We all the participants and their We the research and healthcare and social-care who to up and the study at all of the and 25 research across the UK, as as all the at the Research Health Research Research of Health and Health Scotland and Health England, and support from the We at the for Research for support in the The PHOSP-COVID was to provide and support in and we the of the as for We are to all the that have provided to the Research UK, UK, UK, Research UK, UK, UK, and the We the Research and and For the of the has a to any from has on a of UK and COVID-19 all these were that their was a from to the from and and to their from and that their was a from the UK Research and and support from to the from of and Research and for and and for The the from to the to support a study of remote rehabilitation after COVID-19. is by an from and research support from and from and the also the for and to attend from the from and during the of the and from and the All other no