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Hospitalizations and mortality during the first year of the COVID-19 pandemic in Hong Kong, China: An observational study

Summary Background Hong Kong followed a strict COVID-19 elimination strategy in 2020. We estimated the impact of the COVID-19 pandemic responses on all-cause and cause-specific hospitalizations and deaths in 2020. Methods Interrupted time-series analysis using negative binomial regression accounting for seasonality and long-term trend was used on weekly 2010–2020 data to estimate the change in hospitalization risk and excess mortality occurring both within and out of hospitals. Findings In 2020, as compared to a 2010–2019 baseline, we observed an overall reduction in all-cause hospitalizations, and a concurrent increase in deaths. The overall hospitalization reduction (per 100,000 population) was 4809 (95% CI: 4692, 4926) in 2020, with respiratory diseases (632, 95% CI: 607, 658) and cardiovascular diseases (275, 95% CI: 264, 286) contributing most. The overall excess mortality (per 100,000 population) was 25 (95% CI: 23, 27) in 2020, mostly among individuals with pre-existing cardiovascular diseases (12, 95% CI: 11, 13). A reduction in excess in-hospital mortality (−10 per 100,000, 95% CI: −12, −8) was accompanied by an increase in excess out-of-hospital mortality (32, 95% CI: 29, 34). Interpretation The COVID-19 pandemic might have caused indirect impact on population morbidity and mortality likely through changed healthcare seeking particularly in youngest and oldest individuals and those with cardiovascular diseases. Better healthcare planning is needed during public health emergencies with disruptions in healthcare services. Funding 10.13039/501100005847Health and Medical Research Fund, Collaborative Research Fund, AIR@InnoHK and RGC Senior Research Fellow Scheme, Hong Kong.


Introduction
Beyond the direct COVID-19 disease burden, estimated at >500 million cases and 6 million deaths by July 2022, there are growing concerns about the indirect impact of interventions to control COVID-19, pandemic-related lifestyle changes, adverse consequences of reorganized health-care systems, and the potential secondary complications of SARS-CoV-2 infections. [1][2][3][4] Public health and social measures such as stay-at-home advisories and movement restrictions have led to delays in healthcare seeking. 5 Medical facilities have been forced to defer routine hospitalizations, consultations or screening appointments to maintain treatment capacity for COVID-19 patients, many of whom require resource-intensive isolation and clinical management, while preventing nosocomial infections. 3 Some individuals may also have hesitated to seek medical care due to fear of COVID-19. 3,6 Treatment-seeking delays risk exacerbation of untreated, non-COVID disease and a more severe average clinical presentation at hospital. Studies from the United States, France and Italy have observed excess deaths in-and out-of-hospital from cardiovascular diseases, diabetes, and other conditions during the pandemic. 2,3,7 Hong Kong implemented a strict COVID-19 elimination strategy in the initial period of the pandemic. 8 After the first imported case was detected on 23 January 2020 followed by an increasing number of imported cases, the government raised the Preparedness and Response Plan to the emergency level. 9 Measures including strict isolation of cases in hospitals or isolation facilities, strict quarantine of close contacts outside the home, travel restrictions, primary and secondary school class suspension, mask mandates, and compulsory social distancing were introduced. 9,10 Hong Kong has an advanced public and private healthcare system whereby private clinics comprise most primary care and government hospitals provide approximately 90% of hospital and related medical services, via the Hospital Authority (HA), at very low cost to patients. 11,12 To minimize hospital congestion and reduce the risk of cross infection, the HA in Hong Kong adjusted service provision to focus on emergency, essential and inpatient services. The number of elective surgeries and selected outpatient services were reduced by approximately half; appointments for non-emergency examinations such as endoscopy and gastroscopy were rescheduled, and some patients were diverted to private hospitals for treatment. 13,14 These measures successful restricted SARS-CoV-2 transmission in the early pandemic to just 7057 local confirmed cases (1 per 1000) and 181 deaths (2 per 100,000) in 2020. However, limited studies addressing the indirect effects of COVID-19 in Hong Kong suggested delays from illness onset to medical contact and from hospital admission to laboratory testing for patients with acute myocardial infarction, and a drastic reduction of pediatric hospitalizations for acute respiratory virus infections. 9,15 The medical impacts of the adjusted healthcare services and behavioural responses to COVID-19 epidemic waves in Hong Kong have not been described. We explored the indirect impact of the COVID-19 pandemic

Research in context
Evidence before this study In addition to the respiratory morbidity and mortality caused by SARS-CoV-2 infection, increasing attention has been focused on the indirect impact of the COVID-19 pandemic and related policy responses on a broader range of public health outcomes. Studies have described hospitalization reductions, including for cardiovascular and respiratory diseases, which logically would be accompanied by increased mortality if life-threatening events fail to receive timely medical intervention. We (HX and JW) searched PubMed on 30 September 2022 using the following search terms: "(("COVID-19") OR ("SARS-CoV-2")) AND (("hospital") OR ("hospitalization") OR ("hospitalizations")) AND (("reduction") OR ("reduce") OR ("reductions") OR ("decline") OR ("declining") OR ("declines") OR ("change") OR ("changes") OR ("different from")) AND (("deaths") OR ("mortality")) AND ("excess")". After title, abstract and full text screening on the 135 studies searched, we identified 31 studies (Summary information of these studies were listed in Supplementary Table 1) that evaluated the impact of the COVID-19 pandemic on overall or cause-specific excess mortality or hospitalizations/procedures/emergency visits, among which two studies described both the changes in hospitalization rates and concurrent changes in cause-specific excess deaths. However, most studies describing all-cause and cause-specific COVID-19 related excess deaths were in jurisdictions applying mitigation rather than containment or strict elimination strategies as employed in Hong Kong where excess health burden can therefore be more reliably attributed to pandemic responses rather than to SARS-CoV-2 infection.

Added value of this study
We analysed all-cause and cause-specific hospitalizations and deaths between 2010 and 2020 in Hong Kong and identified an absolute reduction of 359,790 (4809 per 100,000 population, a 23% reduction) hospitalizations and 1873 (25 per 100,000 population) excess deaths in 2020 which would not have been expected in the absence of the COVID-19 pandemic and associated policy and population responses. Most excess mortality was associated with cardiovascular diseases and among high-risk population groups, indicating target groups for public health intervention in case of future COVID-19 or other epidemics. The observation of decreased in-hospital and increased out-of-hospital mortality in 2020 was suggested to result from the lack of/inability to seek urgent medical care during the pandemic.

Implications of all the available evidence
The indirect impact of the COVID-19 pandemic, likely resulting from concern about SARS-CoV-2 exposure or other challenges to timely access of medical services has caused reduced hospitalization and excess deaths in some jurisdictions and high-risk population groups which may outweigh even the direct consequences of SARS-CoV-2 infection. With the possible emergence of more virulent or transmissible strains of SARS-CoV-2, medical institutions and policymakers should prepare adequate resources, including risk communication, to provide better healthcare for patients with non-COVID-19 diseases.
Articles on healthcare use and population health, indicated by the change in all-cause and cause-specific hospitalizations and deaths in 2020.
Individual death data recorded in Hong Kong from 2010 to 2020, including age, sex, date, primary cause of death and residence, were collected from the Census and Statistics Department of Hong Kong. The age-and sex-specific mid-year population from 2010 to 2020 were extracted from official statistics of the annual census data published by the Census and Statistics Department of Hong Kong. 16

Statistical analysis
Weekly hospitalization and mortality risk was calculated by dividing the number of weekly hospitalizations and deaths by mid-year populations, respectively, by age, sex and cause of admission or death, while the annual risk was estimated using the annual number of hospitalizations and deaths as the numerator. An interrupted timeseries analysis was used to estimate the hospitalization reductions and excess mortality occurring in 2020 through a counterfactual which assumed trends from 2010 to 2019 would continue in 2020. 17 Weekly hospitalization and death data from 2010 to 2018 were fitted to negative binomial regression models separately accounting for seasonality and temporal trends, using the population in Hong Kong as an offset. A group of models were developed using different Fourier terms with or without the variable "week" to explore the impact of seasonality and using calendar year and the week sequence (from the first week of 2010 to the last week of 2018) to indicate the temporal trends. Selection of the final model was based on the model performance which was examined by comparing the model-predicted values with the observed values in 2019 (full model selection process described in Supplementary Materials). The COVID-19-associated annual hospitalization reduction and excess mortality risk in 2020 and the weekly average hospitalization reduction and excess mortality risk during an epidemic wave were estimated from the variances of the weekly hospitalization and mortality risk predicted by the selected model (Supplementary Materials). The results were presented as overall estimates as well as by sex, age, and cause of admission or death. These analyses were repeated to explore the impact of health seeking and access on mortality patterns, using overall and cause-specific a) in-hospital mortality, and b) out-ofhospital mortality, with the Hong Kong population as an offset (Supplementary Materials).
Hong Kong experienced four COVID-19 "epidemic waves" in 2020, each defined as an epidemic after which the local transmission was suppressed, although the fourth wave which started in November 2020 did not end until the spring of 2021. We defined weeks 5-9 as epidemic wave 1, weeks 10-19, weeks 20-42, and weeks 43-53 as wave 2, wave 3 and wave 4, respectively. The weekly average all-cause and cause-specific hospitalization reduction and excess mortality were estimated for waves 1 and 2 (combined), wave 3, and wave 4, using the same aforementioned method, including in-and out-ofhospital mortality estimates for each wave (Supplementary Materials).
The proportion of deaths occurring in hospital was calculated by dividing the in-hospital deaths by the total number of deaths in Hong Kong, and we compared the proportions between 2020 and 2010-2019 using Pearson's chi-square test. We calculated the weekly inhospital mortality risk from 2010 to 2020 by dividing the number of in-hospital deaths by the number of hospitalizations occurring in each week of the year. To identify the change in in-hospital mortality risk in 2020, we estimated the overall, age-and sex-specific excess inhospital mortality risk using a similar negative binomial regression model as used for the overall excess mortality estimation, with the number of hospitalizations as an offset (Supplementary Materials). Analyses were conducted in R version 4.1.0 (R Foundation for Statistical Computing, Vienna, Austria).

Excess deaths
Between 2010 and 2019, a slightly increasing trend in population mortality risk was identified from 589 (per 100,000 population per year) in 2010 to 639 in 2019 (Fig. 4A). In 2020, the mortality risk was 661 per 100,000, higher for males (796) than females (548). The three leading causes of death were malignant neoplasms (197 per 100,000 per year), respiratory diseases (151), and cardiovascular diseases (137).

Discussion
We conducted an interrupted time-series analysis of hospitalizations and deaths from 2010 to 2020 in Hong Kong and identified a significant reduction in hospital admission, an increase in mortality and changing patterns of deaths coinciding with SARS-CoV-2 circulation and accompanying public health and social measures. These findings are indicative of changing patterns of healthcare use associated with the COVID-19 pandemic as observed elsewhere, 6,18-21 which may have resulted in an increase in preventable, non-COVID-19 mortality in Hong Kong. Our study observed an overall reduction of 4809 (95% CI: 4692, 4926) hospitalizations per 100,000 population in 2020 particularly in respiratory diseases at the two extremes of age (Figs. 2 and 3). The observed decline in respiratory infections during the pandemic was likely due to the public health responses to the COVID-19 pandemic 10 while changes in healthcare seeking behaviors might also contribute to the observed disease burden. While we lack data to describe the underlying population behaviour or healthcare factors potentially contributing to these changes, data from Hong Kong and other countries may have suggested some likely mechanisms. First, individuals might have a fear of exposure to SARS-CoV-2 by changing their behavior to minimize social contacts, and were reluctant to seek medical care. These behavioral modifications were likely magnified during periods of the strictest social distancing including school suspensions and restricted public gathering, concurrent with alarming media reports on exposure risk and its consequences. 3,6,22,23 This effect has been documented by a study in the UK describing reluctance to seek medical care due to fear of COVID-19, 24 the consequence of which would be a more serious average clinical presentation at hospital and a proportion of patients failing to receive the treatment that they needed. 25 Second, the difficulty in accessing medical care due to reorganized healthcare services, deferral of milder cases, elevated emergency triage thresholds and reduced ICU capacity would have resulted in lower utilization of non-COVID healthcare. 6 Although these measures helped control nosocomial infection of COVID-19, the stringent infection control measures might have discouraged patients from accessing care, resulting in elevated fatality risk from acute and life-threatening conditions such as myocardial infarction. 15 We identified a notable hospitalization reduction and a higher inhospital mortality risk in 2020, indicative of reluctance to seek healthcare and perhpas an increased severity among admitted patients, particularly older adults, which supports the hypothesis of changing care-seeking and stricter admission thresholds during the outbreak. Telemedicine may be a useful alternative to improve access to healthcare during the pandemic 26 while the implementation barriers should be addressed to ensure health equity in the population. 27 We also observed a declining trend of hospitalization reduction through 2020 consistent with declining adherence to voluntary social distancing measures and "epidemic fatigue" resulting in healthcare use patterns more similar to previous years. 10,28 Besides, the experience from the early COVID-19 pandemic suggested that better management in healthcare system might help mitigate the indirect negative impact of the pandemic on population health. 29 Despite the hospitalization reductions identified among cardiovascular and respiratory diseases, we did not observe comparable reductions in hospitalization for other causes, particularly the malignant neoplasms and kidney diseases with a higher hospitalization rate than cardiovascular and respiratory diseases in 2020. This is likely because while there was a planned reduction in almost half of the elective surgeries and some outpatient services in public hospitals, treatment of some diseases such as cancer was unaffected. 13,14 The perceived severity and clinical consequences of untreated diseases such as malignant neoplasms and kidney diseases might also have outweighed any impulse to avoid healthcare facilities for fear of SARS-CoV-2 infection.

Articles
In a scenario with reduced and delayed hospitalizations as outlined above, it is reasonable to expect an increase in mortality caused by late treatment seeking for potentially life-threatening disorders. Excess deaths were observed in our study concurrent with COVID-19 epidemics, in agreement with studies conducted in other regions. 7,17,30 While COVID-19 may aggravate existing cardiovascular disease, 31,32 infections were closely tracked in Hong Kong, and we believe the most likely explanation for excess deaths was the indirect impact of the COVID-19 pandemic. Most excess deaths occurred among older people with cardiovascular diseases without inpatient treatment, consistent with an Italian study indicating a significant increase in out-ofhospital cardiac deaths during the pandemic. 33 The risk of mortality can increase over time due to clinical complications for conditions such as atrial fibrillation, and early use of reperfusion therapy is needed for patients with acute coronary syndromes 34 and delays in reperfusion following some acute cardiac conditions have contributed to a significant increase in out-of-hospital cardiac deaths during the COVID-19 pandemic. 6 This treatment dynamic possibly explains the lag effect observed in our study whereby reduced hospitalizations in early 2020 were followed by excess cardiovascular deaths later in the year, but other reasons such as postponed scheduled interventions or consultations in older adults with existing illness, and increased psychological stress triggering cardiac events, are also possible. 3 We studied the indirect impact of the COVID-19 pandemic using a comprehensive sample of causespecific hospitalizations and deaths in a region where a strict elimination strategy was implemented to cope with COVID-19 but our study has four distinct limitations. First, it is possible some observed reductions in hospitalization sought care in private hospitals while our study was based on hospitalizations in public hospitals which constituted over 90% of all hospital admissions in Hong Kong. The declined hospitalization illustrated in our study might have overestimated reductions in careseeking during the COVID-19 pandemic. Second, our analysis on in-hospital deaths did not include deaths in accident & emergency or private hospitals, potentially leading to an underestimate of the in-hospital mortality and an overestimate in the out-of-hospital mortality. Third, we did not model concurrent healthcare system or behavioural changes occurred in 2020 in Hong Kong that might also have contributed to the changing patterns in hospitalization and death. Finally, we included only the primary diagnosis for hospitalization or the disease or condition leading directly to death, omitting contributing causes which in some fatalities may provide additional information on the relationship between changes in hospitalization and deaths.
In conclusion, the hospitalization reductions and excess deaths identified in Hong Kong in 2020 indicated the potential indirect impact of the COVID-19 pandemic on population morbidity and mortality. Studies during future COVID-19 epidemics and other public health emergencies are needed to provide further evidence on the relationship between healthcare seeking and health impact in the population.