Objective:

To determine whether household contacts of confirmed cases of COVID-19 have an increased risk of hospitalisation or death.



Methods:

We used the HOSTED dataset of index cases of COVID-19 in England between June and November 2020, linked to Secondary Uses Service data on hospital episodes and Office for National Statistics’ mortality data. Multivariable logistic regression models of the odds of household contacts being hospitalised or dying within six weeks of an index case, adjusted for case type, age, sex and calendar month were calculated. Excess risk was determined by comparing the first six weeks after the index case with 6-12 weeks after the index case in a survival analysis framework.



Results:

Index cases were more likely to be hospitalised or die than either secondary cases or non-cases, having adjusted for age and sex. There was an increased risk of hospitalisation for non-cases (adjusted hazard ratio (aHR) 1.10 (95% CI 1.04, 1.16)) and of death (aHR 1.57 (95% CI 1.14, 2.16)) in the first six weeks after an index case, compared to 6-12 weeks after.



Conclusion:

Risks of hospitalisation and mortality are predictably higher in cases compared to non-cases. The short-term increase in risks for non-case contacts following diagnosis of the index case may suggest incomplete case ascertainment among contacts, although this was relatively small

Dabrera, Gavin

Dunbar, J Kevin

Hall, Jennifer A

Harris, Ross J

Zaidi, Asad

English

UCL Discovery

Journal Pre-proofRisk of hospitalisation or death in households with a case of COVID-19 in England: ananalysis using the HOSTED datasetJennifer A. Hall, Ross J. Harris, Asad Zaidi, Gavin Dabrera, J Kevin DunbarPII: S0033-3506(22)00208-6DOI: https://doi.org/10.1016/j.puhe.2022.07.013Reference: PUHE 4666To appear in: Public HealthReceived Date: 11 April 2022Revised Date: 16 July 2022Accepted Date: 19 July 2022Please cite this article as: Hall JA, Harris RJ, Zaidi A, Dabrera G, Dunbar JK, Risk of hospitalisationor death in households with a case of COVID-19 in England: an analysis using the HOSTED dataset,Public Health, https://doi.org/10.1016/j.puhe.2022.07.013.This is a PDF file of an article that has undergone enhancements after acceptance, such as the additionof a cover page and metadata, and formatting for readability, but it is not yet the definitive version ofrecord. This version will undergo additional copyediting, typesetting and review before it is publishedin its final form, but we are providing this version to give early visibility of the article. Please note that,during the production process, errors may be discovered which could affect the content, and all legaldisclaimers that apply to the journal pertain.Crown Copyright © 2022 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.   Risk of hospitalisation or death in households with a case of COVID-19 in England: an analysis using the HOSTED dataset   Authors and affiliations Jennifer A Hall COVID-19 National Epidemiology Team 1 Ross J Harris Statistics, Modelling and Economics Department 1 Asad Zaidi COVID-19 National Epidemiology Team 1 Gavin Dabrera COVID-19 National Epidemiology Team 1 J Kevin Dunbar COVID-19 National Epidemiology Team 1  1UK Health Security Agency, London, United Kingdom.  Corresponding author Ross J Harris  Modelling and Economics Department UK Health Security Agency 61, Colindale Avenue London NW9 5EQ  Email: Ross.harris@phe.gov.uk Phone: +442083276428   Conflict of interest statement  None declared  Journal Pre-proof1  Abstract 1 Objective 2 To determine whether household contacts of confirmed cases of COVID-19 have an increased risk of 3 hospitalisation or death. 4 Methods 5 We used the HOSTED dataset of index cases of COVID-19 in England between June and November 6 2020, linked to Secondary Uses Service data on hospital episodes and Office for National Statistics’ 7 mortality data. Multivariable logistic regression models of the odds of household contacts being 8 hospitalised or dying within six weeks of an index case, adjusted for case type, age, sex and calendar 9 month were calculated. Excess risk was determined by comparing the first six weeks after the index 10 case with 6-12 weeks after the index case in a survival analysis framework. 11 Results 12 Index cases were more likely to be hospitalised or die than either secondary cases or non-cases, 13 having adjusted for age and sex. There was an increased risk of hospitalisation for non-cases 14 (adjusted hazard ratio (aHR) 1.10 (95% CI 1.04, 1.16)) and of death (aHR 1.57 (95% CI 1.14, 2.16)) in 15 the first six weeks after an index case, compared to 6-12 weeks after. 16 Conclusion 17 Risks of hospitalisation and mortality are predictably higher in cases compared to non-cases. The 18 short-term increase in risks for non-case contacts following diagnosis of the index case may suggest 19 incomplete case ascertainment among contacts, although this was relatively small.Abstract word 20 count: 215 21   22 Journal Pre-poof2  Introduction 23 The Household Transmission Evaluation Dataset (HOSTED) [1] provides a unique opportunity to 24 explore the risk of hospitalisation and death in household contacts of confirmed cases of COVID-19 25 to determine if there is any excess risk to them, regardless of whether they are diagnosed with 26 COVID-19 themselves. This is particularly important in the scenario of limited testing where cases 27 may be missed, as was the case in England early in the pandemic.  28 Methods 29 The HOSTED methodology has been described elsewhere[1]; in brief, it is an ongoing surveillance 30 system that has identified the residential household contacts of laboratory confirmed cases in 31 England since 20th April 2020, including both Pillar 1 ( testing of persons for a clinical need in 32 healthcare or as part of a public health investigation) and Pillar 2 (community-based testing 33 accessible to members of the public). Linkages with  hospital episodes from Secondary Uses Service 34 (SUS) data (a national administrative dataset based on healthcare providers’ clinical activities)  and 35 ONS (Office for National Statistics) mortality data for all anonymised cases and contacts within 36 HOSTED enable us to investigate whether there is any increase risk in hospitalisation or death for 37 household contacts of confirmed cases of COVID-19.  38 There is very limited evidence on hospitalisation and deaths of household contacts of confirmed 39 COVID-19 cases. Data from a cohort study in Scotland has shown that between 1st March and 6th 40 June 2020 household contacts of cases of COVID-19 in the general public had a risk of admission 41 with COVID-19 of 0.05%; it was higher for healthcare workers and their household contacts[2].  42 We considered individuals in households where the index case occurred between 1st June 2020 and 43 8th November 2020, extracted on the 31st January 2021, to allow for complete follow up of 44 hospitalisations within six weeks of the index case, and a further six weeks buffer in case of reporting 45 delays in the SUS data. Hospitalised individuals were grouped using ICD-10 codes in to “COVID” (U07 46 and derivatives), “pneumonia (B97 and J12) and possible interest”, and “other” (all other ICD-10 47 Journal Pre-proof3  codes). ICD-10 codes of ‘possible interest’ were co-morbidities thought to be risk factors for adverse 48 outcomes of COVID-19 on discussion with clinicians. This predominantly included diseases of the 49 cardiovascular, cerebrovascular, respiratory and renal systems, cancer, diseases that cause 50 immunosuppression or require treatment with immuosuppressives, diabetes, and obesity. The 51 pneumonia codes were selected in case of misdiagnosis of a COVID-19 case as another viral 52 pneumonia. This grouping together captured people in whom a diagnosis of COVID-19 could have 53 been missed. We had data on whether the person had died, but not their cause of death. 54 Statistical analysis 55 The proportion hospitalised or dying within 6 weeks of the index case testing positive (starting from 56 the specimen date of the positive test) was modelled using logistic regression; covariates included 57 case category (index case, secondary case, contact without positive test), age group (0-34, 35-54, 55-58 69 and 70+) and sex. Time trends were considered by including calendar month, and age-specific 59 trends. In order to ascertain whether there was any excess risk of hospitalisation in non-cases, we 60 examined hospitalisation rates in the first six weeks after the index case compared to 6-12 weeks in 61 a survival analysis framework. Hazards were assumed constant within each time interval and 62 estimated hazard ratios (HR) adjusted for age, sex and calendar time. Analysis was restricted to 63 patients with 18 weeks observable follow-up. 64 Ethics approval  65 The HOSTED surveillance system was reviewed and approved by the PHE Research Ethics 66 Governance Group.  The data was collected and linked by NHS Digital.  The data was processed 67 lawfully under GDPR Article 6(1)e and 9(2)i and shared under Regulation 3(4) of the Health Service 68 (Control of Patient Information) Regulations 2002.     69  70 Journal Pre-proof4  Results 71 In England there were 1.68 million individuals living in a household in which a confirmed case 72 occurred between 1st June and 8th November 2020. The median household size was 4 (interquartile 73 range, IQR: 3-5); the median age of individuals in the dataset was 32 (IQR 19-50), with 326,606 74 children under age 16 (19.4%) and 63,994 age 70+ (3.8%). In 74.5% of the data for this time period, 75 the index case occurred in October/November, when cases were increasing rapidly in England, but 76 before the emergence of the Alpha variant. 77 Hospitalisation 78 49,516 individuals (2.95%) were hospitalised within 42 days of the index case date.  28,843/477,034 79 (6.05%) index cases were hospitalised and 4,685/92,243 (5.08%) secondary cases. In comparison, 80 among household contacts without laboratory diagnosed COVID-19, 13,876 were hospitalised out of 81 1.05 million (1.32%).  82 In logistic regression of all persons in the dataset, index cases were most likely to be hospitalised 83 (aOR 4.49 95%CI 4.40, 4.59) compared to non-cases, after adjusting for age and sex, as were 84 secondary cases (aOR 3.54 95%CI 3.40, 3.65). Rates of hospitalisation increased with age, as did the 85 risk associated with being a case compared to a contact, regardless of reason for admission. Of those 86 aged over 70, 27.9% were admitted with COVID-19 within six weeks of laboratory confirmation and 87 4.14% were admitted with pneumonia or other potentially relevant ICD-10 code, compared to 1.26% 88 and 0.35% respectively in index cases aged 0-34. Among household contacts who were not 89 laboratory confirmed COVID-19 cases, 0.35% of over 70s were admitted with COVID-19, 3.18% with 90 pneumonia or other relevant condition and 0.58% for other reasons, according to the SUS data. For 91 every age group the percentages of non-COVID-19 admissions are higher in COVID-19 cases than 92 those not diagnosed with COVID-19. 93 Journl Pre-proof5  Hospitalisations due to any cause in index cases of COVID-19 fell in all age groups from June to 94 October 2020, though the risks decreased most for those under 35. Hospitalisation in non-cases also 95 fell slightly in every age group between June-October 2020, and younger age groups were 96 consistently more likely to be hospitalised for reasons other than COVID-19/pneumonia.  97 Examining only the non-COVID-19 admissions, both index and secondary cases were more likely to 98 be admitted to hospital in the six weeks following a positive test for SARS-CoV-2, particularly if they 99 were over 70 years old, both for pneumonia/other relevant conditions or for another reason. 100 Mortality 101 6,414 individuals (0.38%) died within 42 days of the index case date. 5,230 of 477,034 index cases 102 died (1.10%), 596 of 92,243 secondary cases died (0.65%), and 419 of 1.05 million non-cases died 103 (0.04%).  104 Death was considerably more likely in index cases (aOR 22.9 95%CI 20.7, 25.3) and secondary cases 105 (aOR 13.1 95%CI 11.5, 14.8) than in individuals not diagnosed with COVID-19, having adjusted for 106 age and sex. In terms of trends, risk of death in index cases reduced over time with a similar pattern 107 to hospitalisation, with the greatest reduction over time in the younger groups. Trends are more 108 stable for secondary cases, although data are sparse and confidence intervals wide. For those not 109 diagnosed, there are declining trends in the youngest and oldest age groups, similar to 110 hospitalisations, but confidence intervals are wide and the results are not significant. 111 Excess risk 112 The adjusted hazard ratio (HR) for hospitalisation within six weeks vs. 6-12 weeks was 1.10 (95% CI 113 1.04, 1.16), indicating a modest increase in hospitalisation rates in non-cases around the time of the 114 index case. For mortality, the adjusted HR was 1.57 (95% CI 1.14, 2.16) for the first six weeks after 115 Journal Pre-proof6  the index case compared to 7-12 weeks after. As shown in Figure 1, this was driven by increased 116 hospitalisation and deaths in the over 55s. 117 <<< FIGURE 1 HERE >>>> 118 Discussion 119 Index cases had the highest risk of hospitalisation and death followed by secondary cases compared 120 to household contacts who did not become laboratory-confirmed cases (non-cases). The higher risk 121 in index cases could be due to testing being biased towards more severe index cases, whereas case 122 ascertainment may be less dependent on severity for secondary cases.  123 We found some evidence of a modest increase risk of hospitalisation in household contacts of 124 laboratory confirmed cases of COVID-19 who did not become laboratory confirmed cases 125 themselves. This suggests that, over the timeframe considered, case ascertainment has been good, if 126 not complete. We found a higher risk of admission than the Scottish study which is likely because we 127 included all hospitalisations, not only those for COVID-19(2). 128 Mortality may be increased by around 50% in non-cases immediately following the index case, 129 although absolute mortality rates remain low and confidence intervals for any excess risk were 130 relatively wide. This may indicate incomplete case ascertainment if a person died before being 131 tested. Routine post-mortem testing for SARS-CoV-2 could reveal the true burden of the disease[3]. 132 Strengths and Limitations 133 The HOSTED dataset is large, covering all laboratory confirmed cases and their household contacts in 134 the England. However, as a passive surveillance system, the data are subject to a number of 135 limitations, including incomplete case ascertainment and a lack of information on testing uptake 136 which could introduce bias. Without genomics data we cannot confirm household transmission 137 versus secondary cases having acquired their infection elsewhere. However, self-isolation of 138 households following COVID-19 symptoms even prior to confirmation reduces the likelihood of 139 Journal Pre-proof7  acquiring an infection outside of the household. Previous sensitivity analysis showed that secondary 140 attack rates within the household were robust to changing the definition of a secondary case from 2-141 14days after the index case to 4-14 days after the index case. 142  143  144  145  146   147 Journal Pre-proof8  Funding  148 This work was undertaken as part of the core functions of Public Health England in relation to the 149 surveillance of communicable diseases and outbreak response. Funding: None 150  151 Conflict of interest statement  152 None declared 153  154 Acknowledgements  155 The authors wish to thank Heather Pinches, Phillip Bowker and Paul Ellingham as well as the rest of 156 the NHS Digital team whose hard work and dedication enabled the creation of these data during the 157 UK Covid19 pandemic response. The authors also wish to thank Sarah Woodhall for her integral role 158 in developing the HOSTED project. 159  160 Data Availability Statement  161 The data underlying this article cannot be shared publicly due to the legal and policy controls placed 162 on data used as part of the government’s response to the Covid19 pandemic.    163  164  165  166  167  168   169 Journal Pre-proof9  References 170  171 1. Hall JA, Harris RJ, Zaidi A, Woodhall SC, Dabrera G, Dunbar JK. HOSTED-England's Household 172 Transmission Evaluation Dataset: preliminary findings from a novel passive surveillance system of 173 COVID-19. Int J Epidemiol 2021. 174 2. Shah ASV, Wood R, Gribben C, et al. Risk of hospital admission with coronavirus disease 2019 in 175 healthcare workers and their households: nationwide linkage cohort study. BMJ 2020; 371:m3582. 176 3. Hall JA, Harris RJ, Emmett HE, et al. On the sensitivity and specificity of post-mortem upper 177 respiratory tract testing for SARS-CoV-2. J Infect Dis 2021. 178  179   180 Journal Pre-proof10  Figure legend 181  182 Figure 1. Proportion of non-diagnosed contacts hospitalised (any cause) or dying per week since date 183 of index case positive, by age. Y-axis scales vary between panels. 184  185 Journal Pre-proofJournal Pre-proof

Risk of hospitalisation or death in households with a case of COVID-19 in England: an analysis using the HOSTED dataset

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Risk of hospitalisation or death in households with a case of COVID-19 in England: an analysis using the HOSTED dataset

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