Part Ⅰ Angiotensin Converting Enzyme Inhibitors May Increase While Active Vitamin D May Decrease The Risk Of Severe Pneumonia in SARS-CoV-2 Infected Patients With Chronic Kidney Disease On Maintenance Hemodialysis

Abstract

The group most at risk of death due to COVID-19 are patients on maintenance hemodialysis (HD). The study aims to describe the clinical course of the early phase of SARS-CoV-2 infection and find predictors of the development of COVID-19 severe pneumonia in this population. This is a case series of HD nonvaccinated patients with COVID-19 stratified into mild pneumonia and severe pneumonia group according to the chest computed tomography (CT) pneumonia total severity score (TSS) on admission. Epidemiological, demographic, clinical, and laboratory data were obtained from hospital records. 85 HD patients with a mean age of 69.74 (13.19) years and dialysis vintage of 38 (14–84) months were included. On admission, 29.14% of patients had no symptoms, and 70.59% reported fatigue followed by fever—44.71%, shortness of breath—40.0%, and cough—30.59%. 20% of the patients had a finger oxygen saturation of less than 90%. In 28.81% of patients, pulmonary parenchyma was involved in at least 25%. The factors associated with severe pneumonia include fever, low oxygen saturation and arterial partial pressure of oxygen, increased C-reactive protein, and ferritin serum levels, low blood count of lymphocytes as well as chronic treatment with angiotensin-converting enzyme inhibitors; while the chronic active vitamin D treatment was associated with mild pneumonia. In conclusion, even though nearly one-third of the patients were completely asymptomatic, while the remaining usually reported only single symptoms, a large percentage of them had extensive inflammatory changes at diagnosis with SARS-CoV-2 infection. We identified potential predictors of severe pneumonia, which might help individualize pharmacological treatment and improve clinical outcomes.

Keywords

COVID-19; SARS-CoV-2; pneumonia; ACE inhibitors; vitamin D; chronic kidney disease; hemodialysis.

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Introduction

The COVID-19 pandemic has been going on for more than two years, its death toll devastating healthcare systems around the world, and it had already led to the death of nearly 6 million of the world’s population by the end of February 2022. The global fatality rate is currently estimated in most countries to be between 1% and 2%. This changes over time and is dependent on many factors, including the number of tests performed (which helps identify more asymptomatic and mild cases), the dominant virus variant, increased rate of infection in younger people, improvements in health care management, and more recently, the vaccination rate of the population [1].

The group most at risk of death are patients with chronic kidney disease on maintenance hemodialysis (HD) [2]. The 28-day probability of death before commencing field vaccination was 25% for all patients, and 33.5% for subjects who were admitted into hospitals according to the European Renal Association COVID-19 Database (ERACODA) report [3]. In our previous study, we showed the extremely high mortality of COVID-19 HD patients from the North of Poland, with a fatality rate of up to 43.81% in subjects over 74 years old [4]. In addition, the survivors suffer from a persistent symptom complex called post-COVID-19 syndrome [5]. We demonstrated that as many as 81% of HD patients report that at least one symptom of COVID-19 persists after six months [6]. These symptoms are dominated by fatigue and shortness of breath resulting from permanent pulmonary architectural distortion and irreversible pulmonary dysfunction [7,8]. It translates into a reduction in the quality of life, which in this group of patients remains at a very low level [6,9].

Vaccines significantly reduced the risk of severe disease and mortality during COVID-19 [10]. Today, however, we already know that breakthrough SARSCoV-2 infections develop in some vaccinated HD patients. This is due to the weakening of vaccine immunity over time and the emergence of new, more infectious, and immune-bypassing variants of the virus [11]. In addition, HD patients are characterized by impaired innate immunity and a worse humoral and cellular response to vaccines than the general population [12–14]. Various methods of pharmacological treatment, including inhaled steroids, casirivimab-imdevimab, remdesivir, and tocilizumab are highly hoped for, which, as research shows, if applied early enough, can significantly improve the prognosis [15–18]. Therefore, the need to identify patients infected with SARS-CoV-2 and those who develop pneumonia, which may be fatal or have persistent sequelae, remains as urgent as possible. Studies conducted in the general population identified the following predictors for COVID-19 pneumonia: older age, obesity, higher fever at presentation, hypoxemia, laboratory markers of inflammation, and lymphopenia [19–21]. The aim of the study below is to describe the clinical course of the early phase of SARS-CoV-2 infection in HD patients and find predictors of the development of COVID-19 severe pneumonia in this population.

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Materials and Methods

1. Study Design and Settings

This is a case series of HD patients with COVID-19 conducted at the 7th Naval Hospital in Gda ´nsk. Through a decision of the local health authorities, all HD patients from the Pomeranian Voivodeship with SARS-CoV-2 infection during the second wave of the pandemic were obligatorily hospitalized and hemodialyzed in a dedicated unit at the 7th Naval Hospital [4]. We included all individuals aged 18 years and older with laboratory confirmation of SARS-CoV-2 infection and available chest CT scan on admission, hospitalized between 6 October 2020 and 28 February 2021. The study patients were not vaccinated against COVID-19. The vaccination process for dialysis patients in Poland was only initiated in late January 2021. Stratification based on median chest computed tomography (CT) COVID-19 pneumonia total severity score (TSS) on admission divided the cohort into a severe changes group with extensive inflammatory changes (severe pneumonia) and a mild changes group with limited inflammatory changes (mild pneumonia).

2. Definitions

Laboratory confirmation for SARS-CoV-2 infection was defined as a positive result of the RT-PCR assay of a nasal or pharyngeal swab. COVID-19 pneumonia was diagnosed by the presence of opacity on chest CT in an amount exceeding 1% of the lungs and confirmed by a radiologist’s assessment. The Charlson comorbidity index (CCI) was calculated by summing the assigned weights of all comorbid conditions presented by the patients, according to the formula of Charlson et al., on admission [22]. The frailty index was calculated on a scale of 1–9, according to the Clinical Frailty Scale, and applies functional descriptors and pictographs. An index of 1 represents very fit, and 9 represents terminally ill [23].

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3. Data Collection and Procedures

Epidemiological, demographic (age, sex), admission clinical and laboratory data, chest CT findings, and outcomes were obtained from the patient’s hospital records. All data were verified by two physicians (E.P.-R., A.P.). All CT scans performed in the first 24 h of hospitalization were evaluated by CT pneumonia analysis software by Siemens Healthineers providing automatic segmentation and quantification of lungs, lobes, and affected areas (volume and percentage) in the lung parenchyma like ground-glass opacities, consolidation, crazy paving pattern, etc. According to this scale, each of the 5 lung lobes was assessed for the percentage of lobar involvement. If the parenchymal involvement was 0, 1–5%, 5–25%, 25–49%, 50–75% and >75% they were assigned a score of 0, 1, 2, 3, 4, and 5 respectively. The TSS was reached by adding the 5 global scores to each other (range from 0 to 25) [24]. A specialist radiologist (A.S.) with long professional experience made additional assessments and possible corrections to the obtained results.

4. Statistical Analyses

Continuous measurements are presented as mean (SD, standard deviation) if they were normally distributed or median (IQR, interquartile range) if they were not, and categorical variables are presented by numbers and percentages. No imputation was made for missing data. In strata analyses of factors associated with severe COVID-19 pneumonia, the median TSS of 7 points was used as the cut-off value. Due to the small number of cases and exploratory character of the research, multivariate analyses were not performed. The Mann-Whitney U test, t-test, and Chi-Square test were applied to analyze differences between groups according to the data type. All analyses were performed using the software Statistica 13. p < 0.05 was considered significant.

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Piotr Tylicki 1, Karolina Polewska 1, Aleksander Och 1,Anna Susmarska 2 , Ewelina Puchalska-Regli ´nska 3 , Aleksandra Parczewska 3 , Bogdan Biedunkiewicz 1 , Krzysztof Szabat 3 , Marcin Renke 4 , Leszek Tylicki 1,* and Alicja D ˛ebska-´Slizie ´n 1

1. Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland; ptylicki@gumed.edu.pl (P.T.); kpolewska@gumed.edu.pl (K.P.); aleksanderoch@gumed.edu.pl (A.O.); bogdan.biedunkiewicz@gumed.edu.pl (B.B.); adeb@gumed.edu.pl (A.D.-´S.)

2. Department of Radiology, University Center for Maritime and Tropical Medicine, 81-519 Gdynia, Poland; anna.susmarska@gmail.com

3. 7th Naval Hospital in Gda ´nsk, 80-305 Gda ´nsk, Poland; e.puchalska@7szmw.pl (E.P.-R.); puchola@gmail.com (A.P.); k.szabat@7szmw.pl (K.S.)

4. Department of Occupational, Metabolic and Internal Diseases, Faculty of Health Science, Medical University of Gdansk, 81-519 Gdynia, Poland; mrenke@gumed.edu.pl