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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
COVID-19 observations from hospitalized ward patients in the Northern Emirates: A practice only preached


1 Department of Internal Medicine, Sheikh Khalifa General Hospital, Umm Al Quwain, UAE
2 College of Medicine, University of Sharjah, Sharjah, UAE
3 Department of Pathology and Laboratory Medicine, Sheikh Khalifa General Hospital, Umm Al Quwain, UAE

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Date of Submission20-Jan-2022
Date of Decision10-Mar-2022
Date of Acceptance11-Mar-2022
Date of Web Publication20-Apr-2022
 

  Abstract 

Background: The COVID-19 pandemic has established itself as the defining global health crisis of this time. The study describes the clinical profile of hospitalized, non-intensive care unit (ICU) patients with COVID-19 in the UAE during its second wave, through January–March 2021. It also highlights the use of antibiotic stewardship principles in patients admitted with COVID-19. Methods: An observational, retrospective study was conducted at a tertiary care hospital based in the Northern Emirates of UAE. A consecutive sample of 110 acutely hospitalized patients with COVID-19 participated in the study. Pregnant women, patients who were admitted to the ICU, and those receiving antibiotics prior to admission were excluded. Data were collected from the written and electronic health records of included patients and subsequently analyzed using IBM SPSS (v25). Results: Population was 58.2% male with a mean age of 51.2 years; 69.1% had at least one comorbidity and 61.8% had severe COVID-19 disease. Mean white blood cell count was 6.03 ± 2.70 × 109 cells/L with a mean C-reactive protein of 83.3 ± 14.6 mg/L. About 4.2% of the tested (20.9%) blood cultures were positive. Empiric antibiotic use was limited to 9.1% of the population. Conclusion: The UAE population admitted in the second wave of the COVID-19 pandemic was mostly male, older with higher prevalence of comorbidities. Given the limited knowledge of the disease, the calculated clinical measures were taken to bring antibiotic use to an extraordinarily low level, not previously seen during the COVID-19 pandemic.

Keywords: Antibiotics, comorbidities, COVID-19, C-reactive protein, UAE


How to cite this URL:
Qureshi S, Kampani DD, Al-Qutbi TA, Mohamed A, Alfaresi M. COVID-19 observations from hospitalized ward patients in the Northern Emirates: A practice only preached. Adv Biomed Health Sci [Epub ahead of print] [cited 2022 Aug 8]. Available from: http://www.abhsjournal.net/preprintarticle.asp?id=343628





  Background Top


The COVID-19 pandemic has firmly established itself as the defining global health crisis of this time and one of the greatest challenges that we continue to face as a global community. First discovered in December 2019, the world has come a long way since from battling a novel, unknown virus to rolling out international vaccination programs which are working to bring down the morbidity and mortality associated with the disease.

Globally, there is a sharp contrast between COVID-19 status and infection rate rising in many countries with few of them still at the peak of their infection curve whereas the other countries are displaying a downward trend [1]. Infection rates have largely been disproportionate, with some populations affected worse than the others due to a host of reasons ranging from high medical comorbidity profiles to socioeconomic challenges [2]. The absence of a “one-size fits all” strategy makes it essential to learn from the experiences of different centers around the world. Understanding which strategies worked and which strategies have the potential to work from a clinical perspective contributes to advancing global knowledge and pandemic preparedness.

In the UAE, COVID-19 infections have sharply increased with an average of 2803 new infections reported each day, at 75% of its peak (as of January 17, 2022) [3]. These figures are in comparison to the peak noted on January 31, 2021. UAE experienced a sharp increase in the number of cases, colloquially called the “second wave,” during the period from January to March 2021. Prior to this, the initial increase of COVID-19 infection rates or the “first wave” was seen from March to August 2020 [4].

Seven COVID-19 field hospitals were opened across the country in March 2021 [5]. However, in the early phase of the increase, when these field hospitals were still not functional, majority of the case load was borne by the government hospitals who were overwhelmed with the number of cases. Admission criteria for COVID-19 were revised to admit only symptomatic patients through the emergency department, who required clinical monitoring. In line with national guidelines and hospital policies, there was no elective admission with regard to COVID-19 at our institution, due to limited bed availability [6].

Through the pandemic, patients’ clinical profiles (including demographics, history of comorbidities, symptomatology, laboratory markers, and radiological features of disease) were extensively studied. In the USA, 80% of deaths associated with COVID-19 were among adults aged ≥ 65 years with the highest percentage of severe outcomes among persons aged ≥ 85 years [7]. In contrast, in a recent study published from the first COVID-19 center in the UAE, patients were young, had diabetes and/or hypertension, and associated with severe infection as shown by various clinical and laboratory data necessitating intensive care unit (ICU) admission [8]. Thus, there is mounting evidence that specific patient characteristics are associated with increased disease severity and risk.

Furthermore, in clinically deteriorating patients with viral infections, such as those admitted during the second wave, a major concern is usually a secondary or co-infection with bacteria contributing to increased morbidity and mortality. A similar belief about COVID-19 was widely prevalent [9]. Antibiotic stewardship programs, described as a systematic effort to follow evidence-based antibiotic prescription to combat growing antibiotic resistance and overuse, were strongly impacted during the pandemic. Initial reports highlighted the increased rates of antibiotic prescription in COVID-19 patients, despite a lack of direct activity against the causative virus. Several reasons for empiric use of antibiotics in the emergency departments were identified by Pulia et al. [10] in their review; the most particular being the difficulty to differentiate COVID-19 symptoms from other respiratory conditions that require empiric antibiotics, in the absence of rapid testing.

Unfortunately, there is limited knowledge about such prescription practices in the UAE, especially in the context of the pandemic. This study hopes to highlight the use of antibiotic stewardship principles in patients with COVID-19 in Umm-Al-Quwain, by identifying the prevalence of antibiotic use in non-intensive care unit (ICU), hospitalized COVID-19 patients and measuring alongside outcomes of mortality and length of stay in the hospital.

To our knowledge, there has been no formal publication that describes the clinical profile of hospitalized, non-ICU patients with COVID-19 in the UAE during the second wave in 2021. This study, conducted in a tertiary care hospital, additionally aims to retrospectively review the clinical profile of these patients.


  Materials and Methods Top


Ethics

The study was reviewed by the Research Ethics Committee of University of Sharjah (REC 21-07-15-01-S) and approved by the hospital board. Data were collected from the written and electronic health records of included patients within the hospital. Pooled data were anonymized, and confidentiality of patients was maintained throughout the length of the study.

Study design

Selection and description of participants

This clinical observational study included symptomatic confirmed COVID-19 patients admitted to general wards in Sheikh Khalifa General Hospital, Umm Al Quwain (SKGH-UAQ), UAE between January 15 and March 31, 2021. SKGH-UAQ is a federal hospital operated by the Ministry of Presidential Affairs, serving the population of the Umm Al Quwain emirate and adjacent northern emirates of UAE.

Patients who are 20 years old or above and were diagnosed with COVID-19 through a confirmed positive reverse transcriptase–polymerase chain reaction test were included. Pregnant women, patients who were admitted to/transferred to/discharged from the ICU, and patients who were receiving antibiotics prior to admission were excluded from the study.

Sample size calculation with a confidence level of 95% and margin of error of 5% for the population of UAE of 9.89 million in 2020 [11] determined the minimum required sample size to be 384 participants. However, this study includes a total of 128 patients. Every subject meeting the criteria of inclusion has been selected within the specified time frame from January to March 2021 through consecutive sampling. The time frame cannot be extended to include the calculated sample size as the variables of the study are representative of the “second wave” of COVID-19 and are therefore time-sensitive. Moreover, the limitation in hospital bed availability during the specified time frame capped the number of patients for inclusion.

Management protocol

Our protocol for the management of COVID-19 in the wards, with immunomodulator, antiviral, and prophylactic anti-coagulant drugs, was based on national guidelines set by the UAE Ministry of Health and Prevention, published on 27th December 2020 [6].

Data collection

Data covered the following sections: (i) demographic data (age, gender); (ii) preexisting chronic comorbidities such as diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), chronic lung disease, chronic kidney disease (CKD), stroke/transient ischemic attack (TIA), cancer, and any other documented comorbidities; (iii) radiological features on chest X-ray and/or high-resolution computed tomography (HRCT) scan; (iv) COVID-19 disease severity (mild, moderate, severe, critical); (v) laboratory investigations [white blood cell (WBC) count, platelet count, C-reactive protein (CRP), ferritin, D-dimer, blood culture, respiratory panel]; (vi) pharmacological regimens (immunomodulators, anticoagulants, antiviral drugs, supplements, empiric antibiotics); and (vii) duration of stay in the hospital.

Disease severity was classified based on the National Institute of Health COVID-19 Treatment Guidelines: (a) mild disease, if patients have any signs or symptoms of COVID-19 without dyspnea, shortness of breath, or abnormal chest imaging; (b) moderate disease, if patients have evidence of lower respiratory disease by clinical assessment or imaging and oxygen saturation above 94% on room air at sea level; (c) severe disease, if respiratory rate ≥ 30/min, blood oxygen saturation (SpO2) < 94%, the fraction of inspired oxygen (FiO2)] <300, and/or lung infiltrates >50% within 24–48 h; (d) critical disease, if patients have respiratory failure, septic shock, and/or organ failure [12].

The laboratory information collected has the following reference values, uniform across genders: (a) WBC count (4.0–10.0 × 109 cells/L), (b) platelet count (150–450 × 109 cells/L), (c) CRP (0–10.0 mg/L), (d) ferritin (15–200 μg/L), and (e) D-dimer (0–0.49 μg/mL). The respiratory pathogen panel was performed whenever possible, with the primary goal of ruling out influenza infections.

Outcomes

Variables describing the clinical profile of non-ICU, hospitalized COVID-19 patients in the UAE will be described in the context of three outcomes: (a) mortality rate in the ward, (b) length of stay in the hospital, and (c) prevalence of antibiotic use in treatment.

Statistics

Data were imported from Microsoft Excel to IBM SPSS, version 25 (IBM Corp., Armonk, NY, USA), for analysis and interpretation. After applying the exclusion criteria, data for 110 participants were analyzed.

For continuous variables, data have been presented as mean and standard deviation. For specific variables, median and range have also been used to describe central tendency. Categorical variables have been represented using frequencies and percentages. The χ2 test was carried out to test for association between two nominal variables. The non-parametric Kruskal–Wallis test was carried out to assess one of the primary outcomes (length of hospital stay) in relation to severity of disease, followed by post hoc Dunn’s pairwise test. Data were visualized using Canva Chart Designer (Canva®) to prepare the figures. There were no missing data in the variables of this study.


  Results Top


A total of 110 participants were included in the study. Out of these participants, 58.2% (n = 64) and 41.8% (n = 46) identified as males and females, respectively, with a mean age of 51.2 (± 14.6, range = 20–89) years.

The majority of the patients (60.9%, n = 67) had at least one comorbidity, prior to the diagnosis of COVID-19. The type and percentage of patients with their respective comorbidities are represented in [Figure 1].
Figure 1: Graphically represents the distribution of comorbidities in the population of patients admitted with COVID-19 in the general ward between January and March 2021.

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WBC count, platelet count, CRP, ferritin, and D-dimer levels were assessed in admitted patients as prognostic factors, recommended under the UAE Ministry of Health and Prevention (MOHAP) guidelines [6]. They are described in [Table 1].
Table 1: The mean value of laboratory investigations undertaken for patients admitted with COVID-19 in the general ward between January and March 2021.

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Blood culture was performed in 20.9% (n = 23) of the patients, of which 95.6% (n = 22) showed no growth, whereas 4.2% (n = 1) had blood culture positive for Staphylococcus hemolyticus. The investigation was not performed for the remaining 79.1% (n = 87) of the patients; decision was made on clinical assessment. Coinfection with influenza was tested for 52.8% (n = 58) of the patients and was reported as negative in all of them.

Chest X-ray was performed for all patients with the following findings: increased bronchovascular markings (21.8%, n = 24), bilateral opacities (65.5%, n = 72), unilateral lobe opacity (1.8%, n = 2), and no appreciable disease (10.9%, n = 12). HRCT was performed only in 5.5% (n = 6) of the patients, showing diffuse ground-glass opacities in these patients.

The patient’s clinical and radiological assessment determined whether the patient’s disease was classified as mild, moderate, and severe. [Figure 2](a) demonstrates the distribution of patients, further highlighting that majority of the patients had severe COVID-19 disease.
Figure 2: (a) The spectrum of COVID-19 disease in the wards based on the UAE MOHAP guidelines. (b) The limited use of empiric antibiotic therapy in patients admitted to the ward.

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[Table 2] highlights the status of laboratory parameters across the three disease severity categories. Gender differences in disease severity have also been reviewed in [Table 3].
Table 2: The mean and median values of laboratory investigations undertaken for patients admitted with COVID-19 in the general ward during January–March 2021, classified based on the disease severity.

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Table 3: Prevalence of COVID-19 severity based on gender distribution, in non-ICU hospitalized COVID-19 patients in the UAE.

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Three lines of pharmacotherapy were used to manage the patients in our wards: (a) immunomodulators, (b) prophylactic anticoagulants, and (c) antiviral drugs as elaborated in [Table 4]. Empiric antibiotics were used for very few patients as elaborated in [Figure 2](b).
Table 4: Part of the pharmacotherapy used to manage COVID-19 in patients admitted to the ward between January and March 2021, based on UAE MOHAP guidelines.

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The preliminary outcome of the study was to determine mortality on the ward during the duration of the study. About 100% (n = 110) of the patients included in the study who received treatment in the general ward were discharged alive, marking mortality rate in the ward as 0%.

As a secondary outcome, duration of stay was assessed in the ward. The mean duration (in days) of stay from presentation to discharge was 6.2 (± 3.8 days, range = 0–25) days, with a mode of 3 days. Patients with (a) mild disease (4.00 ± 2.45 days), (b) moderate disease (4.70 ± 2.38 days) and (c) severe disease (7.20 ± 4.20 days) showed significant variation in the length of stay. The non-parametric Kruskal–Wallis test showed P < 0.001. Dunn’s pairwise tests were carried out for the three pairs of groups. There was very strong evidence (P = 0.005, adjusted using the Bonferroni correction) of a difference between those with severe and moderate diseases. Similarly, there was a significant difference (P = 0.012, adjusted using the Bonferroni correction) between those with mild and severe diseases.


  Discussion Top


The COVID-19 pandemic ushered in a healthcare crisis that left behind more questions than the ones it answered. In such uncertain times, experience from single centers serves as important pieces in the large puzzle. Our study is the first formal publication to describe the clinical profile of hospitalized non-ICU patients during the country’s second wave. They were mostly male with severe presentation of disease, which led to significantly longer hospital stay. Despite severity of presentation, empiric antibiotic use was limited.

Hannawi et al. [8] conducted a case series study outlining the clinical and laboratory profile of hospitalized symptomatic COVID-19 patients in the first wave of the pandemic in the UAE. It was identified that patients were males (78%), relatively young (49 ± 15 years) and at least one comorbidity was present in 54% of the patients. In comparison, our population in the second wave was older at 51.2 ± 14.6 years with at least one comorbidity in 60.9% of the patients. This highlights a shift in the demographic of the population over the two major waves of the pandemic in the country and underscores the importance of tracking future infection peaks closely to delineate trends in populations most at-risk.

The role of gender response in the pathophysiology of COVID-19 is increasingly being recognized and reported, with greater negative outcomes affecting men [13]. However, our population did not differ significantly in disease severity and recovery, possibly due to limited sample size.

The previous study also identified laboratory and radiological parameters with 35% of the patients exhibiting WBC count below the reference range and 60% of the patients had high D-dimer levels in the first wave of the pandemic. Approximately 64% of their population showed positive radiological findings on chest X-ray [8]. The results of the second wave in the UAE show a comparative decrease in patients with lymphopenia and a steep increase in levels of inflammatory markers: D-dimer, ferritin, and CRP. It is worth noting that 90.1% of the population studied in the second wave showed appreciable disease on chest X-ray.

Although there are no public data on genomic variants of COVID-19 prevalent in the UAE during the same time frame, it can be hypothesized that this shift in inflammatory activity of the disease could be attributed to increased prevalence of the beta-variant of SARS-CoV-2 in comparison to the previously common alpha-variant of the same virus. It is worthwhile to note that the beta-variant was first reported in the world in December 2020 and labeled as a variant of concern [14]. Retrospectively, UAE’s Genetic Testing Registry reported in June 2021 that the beta-variant was the most prevalent at 39.2% [15].

Patients admitted to the ward with COVID-19 during January–March 2021 had failed outpatient care and were rapidly worsening; they were severely sick patients requiring oxygen. Yet less than 5% of the patients at our center were moved to ICU due to requirement of high flow nasal cannula to maintain oxygen levels >94%. This is in sharp contrast to 55% of the patients being shifted to the ICU in the previous study from the first wave in UAE [8]. We followed guidelines for treatment as per UAE’s Ministry of Health and Prevention (MOHAP) updates and treated majority of our hypoxic patients with close observation [6]. The improvement may be credited to a better understanding of the disease, leading to focussed resource optimization during the crisis.

Since the onset of the pandemic, there has been increasing debate about the use of empirical antibiotics to mitigate the risk of morbidity and mortality associated with bacterial co-infections in patients with viral respiratory infections. This led to the use of empirical antibiotics in patients with COVID-19 through the pandemic. In a recently published review, the mean rate of antibiotic use in COVID-19 patients globally was 74.0% of the cases. However, only 17.6% of the patients who received antibiotics had secondary infections and pooled data of four studies highlighted that more than 50% of patients receiving antibiotics were neither severe nor critical [16]. Furthermore, another review study revealed that the overall proportion of COVID-19 patients with bacterial infection is merely 6.5%, with majority in those who were critically ill [17]. Through 2020, we noticed increasing analyses of bacterial co-infections showing an average of 3% community-acquired bacterial superinfection to as high as 14% hospital-acquired superinfection [18]. A regional COVID-19 study also showed similar infection rate data [19].

Comparatively, antibiotic prescription was a mere 9.1% in our population, in line with antibiotic stewardship principles. We based our use of antibiotics on our initial and daily assessments. We clinically assessed our patients for signs and symptoms of bacterial superinfection. Our assessment included the following: (a) cough with sputum production, (b) change in sputum color over the past 48 h, (c) WBC count with neutrophilia, and (d) evidence of dense lobar consolidation on radiography. Our success with minimal use of antibiotics was made possible by daily close observation, a well-informed close team, and daily examination of our patients.

Prior to the COVID-19 pandemic, higher CRP levels have traditionally been considered to be associated with a bacterial infection source [20]. The value of this practice has been called into question in our set of patients. The elevated levels of CRP might be linked to the overproduction of inflammatory cytokines in severe patients with COVID-19. Thus, CRP production is induced by inflammatory cytokines and by tissue destruction in patients with COVID-19. From the perspective of the clinical manifestations, the essence of COVID-19 should be viewed as a sepsis induced by viral infection [21].

The viral sepsis induced by SARS-CoV-2 has the typical pathophysiological characteristics of sepsis, that is, the early cytokine storm and the subsequent immunosuppressive stage. Upon SARS-CoV-2 virus challenge, alveolar macrophages and epithelial cells release a large number of cytokines and chemokines [22,23]. Monocytes and neutrophils may be recruited to the site of infection and clear the exudate containing virus particles and infected cells, which in turn lead to uncontrolled inflammatory response. During this process, adaptive immunity is difficult to start effectively due to the significant decrease in lymphocyte number and T-cell-mediated immune dysfunction. Therefore, a deep understanding of the clinical significance of CRP in the diagnosis, treatment, and prognosis of sepsis in SARS-CoV-2 infection is helpful to the early rationale in using antibiotics [24].

There is growing concern for a potential rise in antimicrobial resistance due to increased antibiotic prescription for COVID-19 patients around the world [17]. The potential of bold strategies, as adopted in our study, paves the way forward to cement existing antimicrobial stewardship programs. A recent study conducted in the UAE identified that 63.4% of the medical professionals follow national health authorities as their primary source of COVID-19 information [25]. Thus, a national framework would serve as a context-specific reference covering education about antimicrobial resistance, tracking local patterns, development of clinical guidelines, and antibiotic control.


  Conclusion Top


The second wave of the COVID-19 pandemic came at a difficult time with challenging patients for the UAE. Our study is the first to describe the clinical profile of hospitalized non-ICU patients during the country’s second wave. The lower mortality in our population compared with the first wave reported earlier could be attributed to better preparedness, more understanding of the virus, experience with COVID-19 patients, and availability of trialed medications. Given the limited knowledge of the new disease, we took bold but calculated clinical measures to maintain antibiotic stewardship practice and brought antibiotic prescribing to an extraordinarily low level previously not seen during the COVID-19 pandemic.

Study limitations

The limitation of this study lies in its relatively small sample size. Combined with its design as a single-center study, there is limited generalizability of the results. Clinical characteristics of asymptomatic patients who constitute a larger proportion of COVID-19 patients are excluded from the scope of this study, which may limit the full picture of our understanding of the disease. Lack of information on post-discharge health status of these patients could be a potential limitation addressed by future studies to expand knowledge on management of this illness.

Acknowledgements

We extend our acknowledgements to Dr. Zuhair Afaneh for his support in facilitating the resources for this study.

Authors’ contributions

SQ conceived the study. SQ, DDK, and TAHA were involved in data collection, facilitated by AM and MA. Methodology was designed by SQ, DDK, and TAHA. DDK performed the formal analysis and TAHA visualized the data. AM and MA were involved in organizing the resources for the project. SQ, DDK, and TAHA were responsible for the original draft of the article. All authors—SQ, DDK, TAHA, and AM, MA—were involved in reviewing and editing the final draft.

Ethical policy and Institutional Review Board statement

The study was reviewed by the Research Ethics Committee of University of Sharjah (REC 21-07-15-01-S) and approved by the hospital board (dated July 12, 2021). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

Data availability statement

All data supporting the findings of this study are available within the article or are available from the corresponding author on request.

Patient declaration of consent statement

Formal ethical approval was taken from University of Sharjah, in addition to no objection certificate from the hospital board.



 
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Correspondence Address:
Drishti D Kampani,
College of Medicine, University of Sharjah, Sharjah
UAE
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abhs.abhs_2_22



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