Andrew Kazibwe,Bonniface Oryokot,Andrew Peter Kyazze,Philip Ssekamatte,George Patrick Akabwai,Emmanuel Seremba,David Mukunya,Magid Kagimu,Irene Andia-Biraro,Robert Kalyesubula
The Effect of COVID-19 Restrictions on General and HIV Positive Inpatient Admissions and Treatment Outcomes: An Uncontrolled Before-and-after Study at a Ugandan Tertiary Hospital
HIV epidemiology,HIV Care continuum,COVID19,Treatment,Health systems,Africa
Measures to contain the Corona Virus Disease 2019 (COVID-19) pandemic curtailed access to prevention and treatment services for endemic infectious diseases like HIV. We used an uncontrolled before-and-after study design to compare general and HIV positive (HIV+) inpatient outcomes at a tertiary hospital in Uganda, using electronic records of medical inpatients. Data was downloaded, cleaned in Microsoft Excel, and exported to STATA for analysis. We determined the difference in number of admissions and median length of hospital stay using Mann-Whitney U test; and difference in median survival and incidence rates of mortality using Kaplan – Meier statistics, between the pre- and peri-COVID-19 groups. Of 7506 patients admitted to Kiruddu NRH, 50.8% (3812) were female and 18.7% (1,401) were aged 31–40 years, and 18.8% (1,411) were HIV+. Overall, 24.6% (1849) died. Total admissions were lower (2192 vs. 5314 patients), overall mortality rate higher (41.8% vs. 17.6%, p < 0.01), median length of hospital stay longer (6 vs. 4 days, p < 0.01) and median survival shorter (11 vs. 20 days, Chi-square = 252.05, p < 0.01) in the peri- than in pre-COVID-19 period. The adjusted hazard ratio (aHR) of death was 2.08 (95% CI: 1.85–2.23, p < 0.01) in the peri- compared to the pre-COVID-19 period. These differences were more pronounced in HIV + patients. Compared to pre-COVID-19, the peri-COVID-19 period registered lower inpatient admissions but poorer treatment outcomes for general and HIV + inpatients. Emerging epidemic responses should minimize disruption to inpatient care, especially for HIV + individuals. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-023-04092-2.
The Effect of COVID-19 Restrictions on General and HIV Positive Inpatient Admissions and Treatment Outcomes: An Uncontrolled Before-and-after Study at a Ugandan Tertiary Hospital

Measures to contain the Corona Virus Disease 2019 (COVID-19) pandemic curtailed access to prevention and treatment services for endemic infectious diseases like HIV. We used an uncontrolled before-and-after study design to compare general and HIV positive (HIV+) inpatient outcomes at a tertiary hospital in Uganda, using electronic records of medical inpatients. Data was downloaded, cleaned in Microsoft Excel, and exported to STATA for analysis. We determined the difference in number of admissions and median length of hospital stay using Mann-Whitney U test; and difference in median survival and incidence rates of mortality using Kaplan – Meier statistics, between the pre- and peri-COVID-19 groups. Of 7506 patients admitted to Kiruddu NRH, 50.8% (3812) were female and 18.7% (1,401) were aged 31–40 years, and 18.8% (1,411) were HIV+. Overall, 24.6% (1849) died. Total admissions were lower (2192 vs. 5314 patients), overall mortality rate higher (41.8% vs. 17.6%, p < 0.01), median length of hospital stay longer (6 vs. 4 days, p < 0.01) and median survival shorter (11 vs. 20 days, Chi-square = 252.05, p < 0.01) in the peri- than in pre-COVID-19 period. The adjusted hazard ratio (aHR) of death was 2.08 (95% CI: 1.85–2.23, p < 0.01) in the peri- compared to the pre-COVID-19 period. These differences were more pronounced in HIV + patients. Compared to pre-COVID-19, the peri-COVID-19 period registered lower inpatient admissions but poorer treatment outcomes for general and HIV + inpatients. Emerging epidemic responses should minimize disruption to inpatient care, especially for HIV + individuals.

The online version contains supplementary material available at 10.1007/s10461-023-04092-2.

The Corona virus Disease 19 (COVID-19), caused by the severe acute respiratory syndrome corona virus – 2 (SARS-Cov-2), was declared a pandemic by the World Health Organization (WHO) in March 2020 [1, 2]. To stem the spread of the pandemic, governments instituted containment measures such as quarantining of infected individuals, restriction of public and private transport, public sensitization; re-purposing and refocusing both human and other healthcare resources [3, 4]. These measures greatly impacted access to and utilization of essential health services, including those for HIV prevention, care and treatment [5]. Indeed, several mathematical modelling studies predicted that COVID-19 restrictions would result in reduced uptake of HIV testing and treatment as measured by the number of individuals tested, individuals newly diagnosed with HIV and linked to and retained on lifelong anti-retroviral therapy [6]. True to these projections, a number of subsequent observational studies reported significant declines in these indicators, potentially reversing gains made towards attaining the UNAIDS targets for ending HIV as a public health threat by 2030 [7, 8]. These declines were heterogenous across countries and population sub-groups largely determined by the intensity of COVID-19 containment measures and approaches to ensure continuity of non-COVID-19 related health services. In Italy for example, there was no significant impact of COVID-19 on HIV viral load suppression rates, and yet this was not the case in Southern USA [9, 10]. In Uganda, Izudi et al. showed that the adaptation of community drug delivery models and multi-month dispensing, limited the impact of COVID-19 on continuity on antiretroviral therapy and hence viral load suppression among PLHIV [3, 11]. One of the major limitations of these findings is that they did not measure the impact of COVID-19 on inpatient services for PLHIV. This limits our understanding of the magnitude of this impact on the entire cascade of HIV care and treatment; and yet Chanda-Kapata et al. emphasise the role of real-world country-specific data to document the impact of COVID-19 on the health care system and inform investments [8]. Not surprisingly, French et al. showed that there were worse outcomes among intensive care unit (ICU) non-COVID-19 patients in the United States of America, and this was attributed to a number of factors. Among these include diversion of health workers from routine ICU to COVID-19 services, non-compliance with standard-of-care guidelines for non-COVID-19 patients, since priority was on provision of emergency care to soaring numbers of critically ill COVID-19 patients; and delayed care-seeking for non-COVID-19 conditions that could have resulted in higher rates of disease progression and complications [12]. The authors contend that COVID-19 restrictions strained hospital capacity to provide care for non-COVID-19 inpatients. Furthermore, Hisham et al. argued that COVID-19 containment measures strained drug supply chain systems potentially resulting in stockouts for essential medicines, and use of alternative treatment regimens that may not have been as efficacious as standard regimens, leading to sub-optimal treatment outcomes [13]. The diversion of GeneXpert machines for multiplex testing for COVID-19 meant that individuals who needed testing for tuberculosis (TB) diagnosis had to wait longer and hence risked complications of delayed TB diagnosis [8]. Humphrey et al. documented that treatment outcomes for patients were suboptimal due to social isolation, COVID-related fear and anxiety and inadequate in-person consultations for patient complaints among patients admitted with terminal illness [14]. While tele-medicine interventions were useful in ameliorating the effects of these challenges, the lack of required robust information technology (IT) capacity to provide near-optimal care to the patients in a number of settings implied that such services were not available to suffering inpatients and their caretakers [14]. Unfortunately, few studies have examined the impact COVID-19 had on inpatient healthcare, more-so among PLHIV. We therefore aimed to determine the impact of COVID-19 on general medical and HIV-related inpatient admissions at a national referral hospital in Uganda, using retrospective data. We studied the differences in in-patient admissions, mortality incidence, median length of hospital-stay, and median survival time between patients admitted in 2019 (pre-COVID) and 2020 (peri-COVID) at this hospital, to provide evidence for better preparedness and management of non-pandemic emergency response health care services and minimise indirect health impacts of the same.

This was an uncontrolled before-and-after study design, using observational data from the pre-COVID-19 period (April to December 2019) and during the peri-COVID-19 period (April to December 2020), downloaded as MS Excel spreadsheets in May 2021.

This study was conducted using electronic medical records on all patients admitted to Kiruddu national referral hospital (KNRH) during the study periods. KNRH was upgraded from a divisional hospital in 2014, to provide specialized medical and plastic surgery services. It is a 200-bed hospital, located in Makindye division in Uganda’s capital city, Kampala [15]. The medical wards are led by specialist physicians and admit seriously ill patients in the respective sub-specialties of nephrology, endocrinology, infectious diseases, cardiology, pulmonology, gastroenterology, hepatology, neurology, hemato-oncology and rheumatology. Records of admitted patients are captured through the Rainer-Arnolds Senior House Officer Training support (RASHOTs) database, that was the data source for this the study. During the COVID-19 outbreak, KNRH screened and referred patients with suspected COVID-19 to national treatment centers, while continuing to provide care and treatment to patients with non-COVID-19-related illnesses. The Uganda Ministry of health instituted strict country wide lockdown measures to contain the spread of the COVID-19 pandemic, starting at the end of March 2020, further tightening these measures in May 2020, with an intermittent period of relative easing in July – September 2020 [3, 16]. This period was followed by a second peak in the number of individuals diagnosed with COVID-19, leading to stricter lockdown measures in October – December 2020. Two national COVID-19 treatment centers were set up at Mulago National referral and Entebbe regional referral hospitals.

We extracted records for all patients admitted to the medical wards of KNRH during the study period (January 2019 – December 2020), from the RASHOTs database. Since the COVID-19 lockdown measures were first instituted in March 2020, we excluded patients admitted in the January – March periods to ensure comparable cohorts and eliminate the effect of seasonal variation.

The primary exposure was, being admitted to KNRH. Secondary variables included age, sex, and HIV status. Age was routinely captured in patient medical records as completed years at the time of admission, rounded to the nearest whole number. HIV status was extracted from patient medical records of test carried out according to Ministry of health guidelines. The outcome variables were mortality (death documented in the electronic record as an outcome of the patient admission, during the study period), median survival time (median time in days between date admission and date of death among those who died) and length of hospital stay (number of days spent in hospital, regardless of outcome) for all admitted. We compared these variables for patients admitted in the pre-COVID-19 restrictions period (pre-COVID-19) and the peri-COVID-19 restrictions period (peri-COVID-19), and did further sub-group analysis for those with and without HIV.

We retrieved and downloaded electronic data for all eligible patients as Microsoft Excel version 19 spreadsheets. We cleaned the data and exported it to STATA BE version 16 for further analysis. We summarized total number of admissions and deaths for each year by patient characteristic and HIV status. Median length of hospital stay in days, was computed by subtracting date of treatment outcome (death or no death) from date of admission. We used the Mann Whitney-U test to compare median length of hospital stay between patient categories and between the pre-COVID-19 and peri-COVID-19 periods. Patient outcomes categorized under “no death” included those discharged, transferred out, and those who left without formal discharge (“run-away”). The date of treatment outcome captured in the medical record was used for censoring observations. We used Chi-square statistics to compare sex, age-group, HIV status and treatment outcome (death or no death) between the pre- and peri-COVID-19 periods. We used Kaplan Meier (KM) survival curves to illustrate differences in survival and the log-rank test to evaluate equality of survivor functions between the pre- and peri-COVID-19 periods. In addition, we computed hazard ratios of death between the two periods, and used Cox proportional hazards model to adjust for sex, age category and HIV status. Median survival time was the time at which half of all patients were still alive, and this was computed from Kaplan – Meier statistics.

This study was nested in the machine learning study, approved by the Makerere University school of medicine, research ethics committee (Number: 2020/098) and the Uganda National Council of Science and Technology (Number: HS745ES). The study was conducted according to the principles of the Declaration of Helsinki, and study participant records were identified using hospital numbers, excluding names. We received a waiver for patient level consent since only secondary data was utilized in the analysis.

In this section, we present the results of our study. In Fig. 1 below, we show that we analysed a total of 7506 records for this study (Fig. 1).

Of the 7506 patients admitted over the study period, 50.8% (3,812) were female, 18.7% (1,401) were aged 31–40 years and there were 18.8% (1,411) who were HIV positive (Table 1). Overall, fewer patients were admitted in the peri-COVID-19 compared to the pre-COVID-19 period (2192 vs. 5314 patients) with a higher proportion of males admitted in the peri- than in the pre-COVID-19 period (51.0% vs. 48.5%, p = 0.05). In addition, while the overall median age of study participants was 45 years (IQR: 31–40 years), patients admitted were older in the peri- than in the pre-COVID-19 period (median age: 47, IQR: 34–63 vs. median: 44, IQR: 30–60 years, p < 0.01). The absolute number of HIV positive patients admitted was markedly lower (390 vs. 1021), and the proportion of HIV positive patients tended to be lower in the peri- compared to the pre-COVID-19 period (17.8% vs. 19.2%, p = 0.15).

The median duration of hospital stay for both study periods was 4 days (IQR: 2–8). There was no difference in overall length of hospital stay between females and males (median = 4 days, IQR: 2–8 vs. median = 4 days, IQR: 2–8, p = 0.92). There were no significant differences in length of hospital stay by age group, but it was longer among HIV positive compared to HIV negative patients (median = 5 days, IQR: 3–8 vs. median = 4 days, IQR: 2–7, p < 0.01). The length of hospital stay was longer in the peri-COVID-19 (median = 5 days, IQR: 3–9) compared to the pre-COVID-19 period (median = 4 days, IQR: 2–7, p < 0.01). While there were no sex differences in changes in length of hospital stay, these were observed in the young patients in the age categories of < 20 years, 21–30 years, whose median length of hospital stay increased from 4 days (IQR: 2–7) in the pre-COVID-19 to 6 days (IQR: 3–9) in peri-COVID-19 period. For those aged 31–40 years, median length of hospital stay increased from 4 days (IQR: 2–7) to 5 days (IQR: 3–8) in the pre-COVID-19 and peri-COVID-19 periods respectively. The older age groups did not experience any changes in median length of hospital stay. Among HIV positive patients, there was no difference in median length of hospital stay between the peri- and pre-COVID-19 periods (median: 5, IQR: 3–8 vs. median: 5, IQR: 3–9 days, p = 0.20).

Overall, 24.6% (1,849/7,506) patients died during the study period, representing a mortality incidence rate of 4.1 per 100 person-days over a total of 44,945 person-days. Overall, mortality among females was 24.1% (918/3,812) and 25.2% (931/3,694) among males (Chi-square = 1.27, p = 0.26). By age group, the highest mortality rate was observed in those aged over 70 years (33.2% (331/996)) followed by those aged 31–40 years (27.4% (384/1,401)) with the lowest among those aged less than 20 years (14.5% (82/567)). Mortality rate was 21.5% (1,310/6,095) and 38.2% (539/1,411) among HIV negative and HIV positive patients respectively (Chi-square = 172.26, p < 0.01). Mortality rate in the pre-COVID-19 period was 17.6% (933/5314) and this rose to 41.8% (916/2192) in the peri-COVID-19 period (Chi-square = 490.78, p < 0.01). Patients admitted in the pre-COVID-19 period contributed 30,385 person-days while those in the peri-COVID-19 period contributed 14,560 person-days. Incidence rate of death was 3.1 per 100 person-days in the pre-COVID-19 and 6.3 per 100 person-days in the peri-COVID-19 period, resulting in an absolute incidence rate difference of 3.2 (95% CI: 2.8–3.7) per 100 person-days and an incidence rate ratio of 2.05 (95% CI: 1.87–2.25). The hazard ratio (HR) of death in the peri-COVID-19 compared to the pre-COVID-19 period was 2.03 (95% CI: 1.85–2.23, p < 0.01) and when adjusted for sex, age category and HIV status the hazard ratio was 2.08 (95% CI: 1.90–2.28, p < 0.01). Similarly, for males compared to females, aHR was 1.08 (95% CI: 0.99–1.19, p = 0.09), and for HIV positive compared to HIV negative patients aHR was 1.82 (95% CI: 1.63–2.03, p < 0.01).

Using Kaplan – Meier statistics, overall median survival time was 16 days (IQR: 8–31), for 7,503 patients (this excludes 3 of the patients whose deaths occurred on the same day of admission and therefore had zero days interval between admission and death). Using the log-rank test, we found no difference in median survival time between females and males (16 days, IQR: 8–31, Chi-square = 1.34, p = 0.25). Median survival time was shorter among HIV positive (12 days, IQR: 5–21) compared to HIV negative patients (18 days, IQR: 9–38) (Chi-square = 89.03, p < 0.01). Median survival time was shorter in the peri-COVID-19 period (11 days, IQR: 5–23) compared to the pre-COVID-19 period (20 days, IQR: 10–38) (Chi-square = 252.05, p < 0.01) (Fig. 2). Similarly, among HIV positive patients, the median survival time was much shorter in the peri-COVID-19 period (6 days, IQR: 3–12) compared to the pre-COVID-19 period (18 days, IQR: 9–29, Chi-square = 191.2, p < 0.01) (Fig. 3).

In this uncontrolled before-and-after study, we compared medical ward in-patient admissions and treatment outcomes at a national referral hospital in Uganda between the pre- and peri-COVID-19 periods. The number of total hospital admissions declined between the two periods, with fewer HIV positive people admitted in the peri- than in the pre-COVID-19 period. Incidence rate of mortality was higher among HIV positive than HIV negative individuals, and more than doubled between the peri-COVID-19 and pre-COVID-19 periods. Overall, patients stayed at least a day longer on the wards in the peri-COVID-19 compared to the pre-COVID-19 period, and the median survival of inpatients reduced from 20 days in the pre-COVID-19 period to 11 days in the peri-COVID-19 period. These changes were more pronounced among HIV positive than among HIV negative patients. The reduction in total hospital admissions between the pre- and peri-COVID-19 periods is similar to what was observed in the United States of America, where COVID-19 pandemic restrictions led to sharp declines in non-COVID-19-related admissions [17]. This decline was likely due to stringent restrictions on human movements and public transport, that characterized Uganda’s COVID-19 countermeasures. This could have deterred individuals from seeking care at this hospital, further compounded by fear of contracting COVID-19 from the hospital environment [18, 19]. Similarly, an Ethiopian study found that fear of potentially catching COVID-19 and transport interruptions constrained hospital visits [20]. The COVID-19-related reduction in healthcare seeking led to reductions in HIV testing and anti-retroviral therapy initiations in South African primary care clinics [21]. These effects mirrored those reported by Tumwesigye et al. who showed reduced hospital attendance across Uganda during the peri-COVID-19 period [22]. They found a 17% drop in outpatient department (OPD) attendance, an important indicator of utilization of health facility services. Conversely, some authors have argued that the reduction in inpatient admissions could have been due to informed choice by both patients and their health workers to defer hospital health care seeking to minimize exposure to COVID-19 [17]. Whereas this could not be ascertained in our study, our findings seem to confirm assertions by the same authors that the delayed care-seeking for non-COVID-19 conditions during the COVID-19 lockdown period could have resulted in progression and development of complications for non-COVID-19 illnesses [17]. This is demonstrated by the poorer treatment outcomes for admitted patients in the peri-COVID-19 compared to the pre-COVID-19 period. We considered three parameters to assess for differences in patient treatment outcomes and these included median length of hospital stay, mortality incidence and median survival time. In terms of length of hospital stay, patients admitted to hospital in the peri-COVID-19 period stayed longer in hospital than those in the pre-COVID-19 period. This could have resulted from admission of very ill patients who required longer in-patient care, as a consequence of disease complications arising out of delayed care seeking from transport restrictions [22]. In addition, the longer duration of hospital stay could also have resulted from diversion of hospital resources to care of COVID-19 patients, which could have resulted in sub-optimal care to other admitted patients, leading to prolonged recovery periods. As was seen in American ICUs, it is plausible that even in KNRH, there could have been failure to comply with standard treatment guidelines occasioned by challenges in drug supply chains, absence of requisite medical expertise to institute appropriate therapy and late diagnosis of medical complications that characterized the peri-COVID-19 period [12]. The same factors could explain the earlier death of admitted patients (as demonstrated by the shorter median survival) and the higher rates of mortality in the peri-COVID-19 period. The fact that the longer hospital stay was more pronounced among HIV positive patients highlights their disproportionate vulnerability to adverse consequences of health system disruptions. Notably, our study found a three-fold increase in mortality among HIV positive individuals, far higher than what was predicted from a modelling study that estimated that HIV deaths would increase by 10% during the peri-COVID-19 period [23]. This highlights the vulnerability of HIV + inpatients to health system disruptions and could have been due to interruption of antiretroviral therapy care, as was shown by two Ugandan studies, where retention in care among PLHIV reduced during the peak of COVID-19 period in Uganda [24, 25]. Further, Chanda-Kapata et al. noted that COVID-19 disrupted normal health service provision, potentially reversing progress attained in controlling not only HIV but also tuberculosis and malaria [26]. On the other hand, some of the patients could have suffered from direct effects of COVID-19 infections. Several studies have suggested that HIV positive individuals co-infected with COVID-19 were more likely to be admitted to hospital and die than their negative counterparts [27–32]. This study however, did not include data on COVID-19 status of admitted patients. Our study has demonstrated the adverse effects the COVID-19 pandemic had on inpatient quality of care indicators at a national referral hospital, more-so among HIV positive patients. This implies that in preparing pandemic response plans, stakeholders need to take into consideration the potential impact of such response plans on individuals seeking care for non-pandemic related illnesses. For this reason, we concur with French et al. who proposed that aggressive, unlike slower scale up of infection prevention and control measures and vaccination are critical at the outset of an epidemic response, to rapidly curtail epidemic spread and hence minimize the strain on hospital human resources and infrastructure, and thus allow for continuity of quality service provision for other conditions, as has been demonstrated in this study [12]. Similarly, Hisham et al., recommended that epidemic response plans should detail continuity plans for non-epidemic-related services such as emergency procurement methods for essential drugs, capacity-building for task-shifting among lower cadres of health workers and provision for tele-consultation to assure timely decision making for optimal patient care [13]. For clients already enrolled in care for chronic disease management programs, home visits and check-in assessment phone calls could facilitate timely screening for and prevention of progression of complications.

Our findings highlight the negative effects of COVID-19 restrictions on hospital admissions as a proxy marker of healthcare seeking; and treatment outcomes as an indicator of quality of care among general and HIV positive patients. These demonstrate that the COVID-19 countermeasures led to reduced healthcare seeking among patients with medical conditions, additional costs to the healthcare system due to longer hospital stay and additional non-COVID-19-related deaths among patients admitted to this national referral hospital. It is therefore important that inpatient services for chronic diseases such as HIV are highly prioritized even during pandemics such as that of COVID-19, to prevent reversal of gains made in reducing preventable morbidity and mortality.

This study had some strengths, including using retrospective service delivery data which allowed for comparison of actual inpatient outcomes between the pre- and peri-COVID-19 periods. This is the first study to document impact of COVID19 restrictions on inpatient outcomes for HIV in our setting. This study was not without limitations. Firstly, we only used data available from the RASHOTs database. This did not include data from the national COVID-19 treatment center based at Mulago National referral hospital nor other semi-autonomous national referral centers such as the Uganda Cancer Institute and Uganda heart institute. This could have resulted in an underestimation of the study outcomes. In addition, our study used electronic medical records of routinely collected inpatient data. It was therefore not possible to study additional patient factors that could have influenced outcomes such as functional status at admission, socio-economic status and number of previous hospital admissions that were not available in our database. Additionally, our study did not include data on the later peri-COVID-19 period (2021) during which COVID-19 vaccination became available and majority of the transport restrictions were lifted. The effect of COVID-19 on the study outcomes could have been attenuated in this period.

Compared to the pre-COVID-19 era, the peri-COVID-19 period was characterized by a reduction in overall inpatient admissions; but higher mortality rates, shorter median survival and longer median hospital stay. These effects were more profound among HIV positive individuals. Future pandemic containment strategies should sustain quality inpatient care for endemic diseases such as HIV, to minimize reversal of gains made. This can be achieved through comprehensive care continuity plans, adoption of tele-medicine approaches, appropriate capacity building for lower health care workers and proactive community follow up of individuals already enrolled in chronic care disease programs.

Below is the link to the electronic supplementary material. Supplementary Material 1