Impact of COVID‐19 pandemic on patients with obstructing urinary stones complicated by infection

Abstract Objective To assess the influence of COVID‐19‐imposed life changes on presentation and outcomes of patients with obstructing urinary stones complicated by infection. Patients and methods All patients presenting with obstructing urinary stones and infection 1 year before the pandemic (March 2019 to February 2020; n = 66) and 1 year since its onset (March 2020 to February 2021; n = 45) were enrolled. Demographics, clinical presentation, laboratory panel, stone characteristics and outcomes were compared between groups. Univariate and multivariate logistic regression models were performed for analysis. Results The COVID‐19 period was characterised by younger patients, female predominance, higher temperature at presentation and more bilateral obstructing stones (p < 0.05). The admission rate to intensive care units was double that of the pre‐pandemic period, whereas time between diagnosis and treatment was similar. The univariate analysis revealed higher rates of severe sepsis (odds ratio [OR] = 3, p = 0.01), systemic inflammatory response syndrome (SIRS) ≥ 2 (OR = 2.9, p = 0.01) and risk, injury, failure, loss of kidney function and end‐stage kidney (RIFLE) criteria ≥ 1 (OR = 2.2, p = 0.04) in the pandemic period group. The multivariate analyses revealed the COVID‐19 period as being the sole variable associated with severe sepsis (OR = 3.1, p = 0.02), SIRS ≥ 2 (OR = 3.8, p = 0.005) and RIFLE ≥ 1 (OR = 2.6, p = 0.05). Conclusions The pandemic period was characterised by a worse clinical state at presentation of patients with obstructing urinary stones complicated by infection, probably reflecting delay in arrival to emergency services.


| INTRODUCTION
The global COVID-19 crisis led to enormous changes in the delivery of healthcare. The lockdowns that were imposed to control disease spread also contributed to difficulties in providing medical care. Public anxiety from exposure to the COVID-19 virus was also contributory to delays in diagnosis and treatment for various non-COVID-19-related emergencies. [1][2][3][4][5][6][7] This situation required reorganisation and modification in both elective and urgent medical prioritisation. Urologists practising in countries strongly affected by the first wave of the pandemic dealt with the immediate need to reclassify the levels of urgency of all key diagnoses and treatments. They produced altered recommendations and guidelines in order to overcome the unique challenges of the pandemic's effects and to ensure effective and timely urologic care. [8][9][10][11] Stone disease, although benign in nature, can have detrimental effects on quality of life by causing pain and leading to disability. It may affect kidney function and carry a substantial risk of infective complications. The kinds of infections related to obstructing urinary stones represent a potentially life-threatening medical emergency requiring urgent antibiotic treatment and kidney drainage. Delay in treatment and diagnosis has proved to be related to increased risk of mortality and morbidity. [12][13][14][15] As such, without exception, all recent guidelines published during the COVID-19 pandemic defined this situation as 'emergent'. [8][9][10][11] Previous studies that had evaluated the pandemic's impact on stone disease showed that there were significantly fewer patients seeking medical aid. [16][17][18][19] However, there is a paucity of information on the presentation for medical assistance on the part of patients with emergent stone-related infection. This study aimed to assess the influence of the COVID-19 pandemic on the presentation, evaluation and outcomes of patients with obstructing urinary stones complicated by infection. The study inclusion criteria were the presence of obstructing ureteral stones diagnosed by non-contrast computed tomography (NCCT) and at least one of the following signs of infection: fever (≥38 C) within 24 h prior the presentation and urine microscopy with ≥500 white blood cells (WBCs) per field and/or positive nitrites. All patients presenting during the pandemic period were assessed by rapid polymerase chain reaction (PCR) tests for COVID-19 at presentation, during hospitalisation and at release from the hospital. Once the diagnosis of a urinary infection was established, the patients underwent kidney drainage by retrograde ureteral stent insertion or, in case of failure of that procedure, by percutaneous nephrostomy.

| Outcomes
Outcomes were analysed by infection severity, admission to the intensive care unit (ICU) and overall hospital stay. Severity of infection was measured by the systemic inflammatory reaction syndrome (SIRS) criteria (negative ≤1 vs. positive ≥2), by severe sepsis as defined by organ dysfunction, hypotension or hypoperfusion and by the presence of bacteremia and/or bacteriuria. [20][21][22][23] Kidney injury was measured by the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) criteria. 24

| Statistical analysis
Descriptive statistics were used to assess patient characteristics. Continuous variables were reported as median and interquartile range (IQR) and compared between groups by means of the Mann-Whitney U test. Categorical variables were reported as frequencies and compared with Fisher's exact and chi-squared tests. Univariate and multivariate logistic analyses were performed to investigate the correlation between study outcomes and timeframe groups. All statistical analyses were two-sided, and significance was defined as p < 0.05. SPSS software (IBM SPSS Statistics, Version 25, IBM Corp., Armonk, NY, USA, 2017) was used for all statistical analyses.

| RESULTS
The study patients' baseline characteristics are summarised in Table 1.
The COVID-19 period group was characterised by younger patients (median age 63.5 vs. 71.5 years for the pre-COVID-19 group, p = 0.02), female predominance (73% vs. 50%, respectively, p = 0.02), higher temperature at presentation (median of 38.1 C vs. 37.6 C, p = 0.04) and more bilateral obstructing stones (18% vs. 9%, p = 0.04). In addition, there was a trend towards increased pain and heart rate, however, not statistically significant (p = 0.08 for both). No differences were found in baseline kidney function as measured by the calculated estimated glomerular filtration rate (eGFR), WBC counts, CRP values and stone characteristics. The time that had elapsed from presentation to NCCT and kidney drainage did not differ significantly between the study groups (p = 0.68 and p = 0.08, respectively). Retrograde drainage by an internal stent was performed in 110 patients, and it failed in one patient who then underwent percutaneous nephrostomy.
The rates of bacteremia, bacteriuria and septic shock were similar for both study groups. The ICU admission rate during the pandemic was double that of the previous period; however, this trend did not reach a level of statistical significance (22% during COVID-19 vs. 11% before COVID-19, p = 0.11). The average hospital stay was 7 days for both groups (p = 0.9). None of the patients in the pandemic era group was COVID-19-positive at presentation nor had become positive during hospitalisation.

| DISCUSSION
The COVID-19 pandemic has been characterised by an exponential increase in the need for hospitalisation, a considerable burden on ICUs for advanced resuscitative interventions, assisted ventilation or use of extracorporeal membrane oxygenation (ECMO) and an expanded number of beds needed for rehabilitation programmes. 25 These sudden changes resulted in quick adaptive measures taken by medical systems, including modifications to the ER triage process, reduction or cancellation of elective medical activities, transfer of medical personnel from other medical fields to the newly organised designated COVID-19 spaces and re-directing much of the medical budgetary resources to fund these alterations. In addition, general national steps, such as lockdowns and quarantining, as well as alarming mass media reports-possibly exaggerated on occasioninduced an atmosphere of panic that resulted in restraints and delays in the public's seeking of medical aid for non-pandemic-related morbidities.
One U.S. study reported that 40.9% of adults having avoided medical care during the pandemic because of concerns about exposure to COVID-19, including 12.0% who avoided urgent or emergency care and 31.5% who avoided routine care. 4 A multicentre study that T A B L E 1 Demographic, clinical and laboratory characteristics at presentation We believe that our comparative study that followed a year-long influence of pandemic on characteristics and outcome of patients  [12][13][14][15]19 We are aware that our study has some limitations. First, it represents the experience of a single tertiary referral medical centre in a highly developed urban region with sufficient resources to cope with regular emergencies as well as the extra burden caused by COVID-19-infected patients. It is possible that the outcomes would have been different in lesser endowed circumstances. However, our experience showed that shifting resources to ensure medical care for pandemic needs and still provide urgent interventions should begin with reducing elective procedures. 27,28 Second, the retrospective design of this study can pose a limitation although we believe that the sudden onset, the unpredictable course, and the confusion among the pandemic prediction models precluded any possibility to initiate a prospective comparison of medical issues related to COVID-19.

| CONCLUSIONS
The first year of the COVID-19 pandemic was characterised by patient delay in seeking emergency care for infections related to obstructive urinary stones as well as by worse clinical states at presentation. Although well-coordinated and optimised resources were able to maintain the capabilities to accommodate these cases with good results, the public will need to be convinced that treatment for other emergencies can be delivered safely without increased risk of COVID-19 exposure.

ACKNOWLEDGMENTS
No other acknowledgements for this study.

CONFLICT OF INTEREST
No competing financial interests exist.

AUTHOR CONTRIBUTIONS
Haim Herzberg was responsible for the design, data acquisition and drafting. Ziv Savin did the statistical assessment. Rinat Lasmanovich performed the data acquisition. Ron Marom did the data acquisition and computerization of data. Reuben Ben-David performed the data acquisition and completion of ethical requirements. Roy Mano did the scientific supervision. Ofer Yossepowitch was responsible for the scientific and ethical supervision. Mario Sofer did the overall supervision and final editing.