T Lymphocyte Subset Counts and Interferon-Gamma Production in Adults and Children with COVID-19: A Narrative Review.

Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously healthy subjects. Understanding these differences is still an ongoing challenge, that can lead to new therapeutic strategies and avoid unfavorable outcomes. In this review, we discuss the different roles of T lymphocyte subsets and interferon-γ (IFN-γ) in the immune responses of adults and children. Lymphopenia can influence these responses and represent a good predictor for the outcome, as reported by most authors. The increased IFN-γ response exhibited by children could be the starting point for the activation of a broad response that leads to MIS-C, with a significantly higher risk than in adults, although a single IFN signature has not been identified. Multicenter studies with large cohorts in both age groups are still needed to study SARS-CoV-2 pathogenesis with new tools and to understand how is possible to better modulate immune responses.

Corrigendum: Definition of the immune parameters related to COVID-19 severity.

[This corrects the article DOI: 10.3389/fimmu.2022.850846.].

A study on clinicodemographic profile, severity, and outcome of Covid-19 in hospitalized vaccinated individuals at tertiary care centre.

Objective: To evaluate the demographic profile, clinical severity, and outcome of Covid-19 infection in hospitalised vaccinated individuals. Methods: An observational, cross-sectional study was conducted among Covid-19 infected hospitalised patients. Clinicodemographic profile, severity, and outcome of Covid-19 infection among the vaccinated group (VG) were recorded. These patients were also compared with unvaccinated group (UVG) with Covid-19 infection admitted during the study period. Cox proportional hazards models was used to estimate hazard ratios for mortality risk in both groups. Results: Out of 580 participants, 48.2% were vaccinated with either one (71%) or two doses (28.9%). In both, VG and UVG, majority 55.8% belonged to 51-75 years. Males were predominant with 62.9% in both VG and UVGs. Day of illness at admission from symptom onset (DOI), progression of disease, ICU stay, oxygen requirement, mortality was significantly higher in UVG than in VG (p < 0.05). Steroid duration (p < 0.001) and anti-coagulation time (p < 0.001) were significantly higher in UVG than in VG. D dimer levels were significantly higher in UVG than in VG (p < 0.05). Increased age, (p < 0.0004), severity of disease, (p < 0.0052), increased oxygen requirement (p < 0.001), elevated C-reactive protein levels (Moderate: P < 0.0013; Severe P < 0.0082), and elevated IL-6 levels (p < 0.001) were the significant determinants of Covid-19-related mortality in both VG and UVGs. Conclusion: Vaccinated individuals have shown milder severity, had reduced hospital stay and better outcomes as compared to unvaccinated individuals suggesting a potential vaccine efficacy against Covid-19.

Postdischarge outcomes of COVID-19 patients from South Asia: a prospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause clinical manifestations that last for weeks or months after hospital discharge. The manifestations are heterogeneous and vary in their frequency. Their multisystem nature requires a holistic approach to management. There are sparse data from the South Asian region on the outcomes of hospital-discharged COVID-19 patients. We assessed the posthospital discharge outcomes of a cohort of Sri Lankan COVID-19 patients and explored the factors that influenced these outcomes. METHODS: Data were prospectively collected from patients who were discharged following an admission to the Nawaloka Hospital, Sri Lanka with COVID-19 from March to June 2021. At discharge, their demographic, clinical and laboratory findings were recorded. The patients were categorised as having mild, moderate and severe COVID-19, based on the Sri Lanka Ministry of Health COVID-19 guidelines. Following discharge, information on health status, complications and outcomes was collected through clinic visits and preplanned telephone interviews. A validated (in Sri Lanka) version of the Short Form 36 health survey questionnaire (SF-36) was used to assess multi-item dimensions health status of the patients at 1, 2 and 3 mo postdischarge. RESULTS: We collected data on 203 patients (male, n=111 [54.7%]). The level of vaccination was significantly associated with disease severity (p<0.001). Early recovery was seen in the mild group compared with the moderate and severe groups. At 3 mo, on average 98% of mild and 90% of moderate/severe patients had recovered. Based on the SF-36, physical functioning dimensions, role limitation due to physical and emotional health, energy/ fatigue, emotional well-being, social functioning, pain and general health were significantly different in the moderate/severe vs mild COVID-19 groups at 1, 2 and 3 mo postdischarge (p<0.05). Twenty-three patients developed complications, of which the most common were myocardial infarction with heart failure (n=6/23; 26.1%), cerebrovascular accident (n=6/23; 26.1%) and respiratory tract infections (n=3/23; 13.01%) and there were six deaths. CONCLUSIONS: In our cohort, receiving two doses of the COVID-19 vaccine was associated with reduced disease severity. Those with mild disease recovered faster than those with moderate/severe disease. At 3 mo posthospital discharge, >90% had recovered.

Assessment and management of the SARS-CoV-2 infection: A secondary center experience: Approach to COVID-19 infection

Aim: The aim of the study was to evaluate the management and outcomes of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital. Material(s) and Method(s): This study included 699 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 on chest computed tomography (CT). Demographics, comorbidities, initial laboratory tests on admission, treatment modalities, complications and outcomes were evaluated retrospectively. Result(s): The mean age was 57.0+/-15.6 (range:16-94 years), and male to female ratio was 1.24;58.7% of the patients had at least one underlying comorbidity, the most common was hypertension;18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% had increased lactate dehydrogenase, and 58.5% had increased D-dimer. Chest CT revealed moderate and severe stages in 57.9% of the patients. Hydroxychloroquine was given to 37.2% and favipiravir to 67.1% of the patients. No significant difference was observed between treatment groups in terms of mortality (P=0.487);5.8% of the patients were transferred to the ICU, 75.6% of whom needed non-invasive and 36.5% invasive mechanical ventilation. The overall case-fatality rate was 0.9. Discussion(s): Older age, male gender, low lymphocyte count, CT findings, including bilateral involvement and severe stage were significantly associated with poor prognosis and mortality.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Why Graded Assessment for Undergraduates during the COVID-19 Lockdown? An Experience Introspection

This paper presents a retrospective evaluation of the Higher Colleges of Technology's student assessments during the COVID-19 lockdown, reflecting the justified decision to deploy graded assessments during the lockdown for students to academically progress and/or graduate on time, while maintaining the quality and rigor of academic awards. The outcome-based evaluation of this paper is intended to provide lessons for any future situations of this significance and magnitude. While online education was the obvious response to the pandemic, the provision of assessments was not possible without risk. Taking a high-stakes decision that would affect the future of thousands of students, for years to come, involved complex steps of reasoning and justification. Addressing the role of graded assessment in supporting institutional accountability and transferability of students' achievements, student efficacy and informed pedagogy alterations were the main objectives. To meet those objectives, the Higher Colleges of Technology was able to deploy an off-campus student assessment model that builds upon three pillars of adjustments (assessment development and deployment, technology infrastructure, and governance resilience) to support students' learning, while mitigating vulnerabilities. The evaluation of student performance indicators and stakeholders' satisfaction rates revealed a successful deployment of off-campus assessment while maintaining the traditional conventions pertaining to evaluation of assessments.

Impact of ACE and Endoplasmic Reticulum Aminopeptidases Polymorphisms on COVID-19 Outcome.

Background: COVID-19 outcomes display multiple unexpected varieties, ranging from unnoticed symptomless infection to death, without any previous alarm or known aggravating factors. Aim: To appraise the impact of ACErs4291(A/T) and ERAP1rs26618(T/C) human polymorphisms on the outcome of COVID-19. Subjects and methods: In total, 240 individuals were enrolled in the study (80 with severe manifestations, 80 with mild manifestations, and 80 healthy persons). ACErs4291(A/T) and ERAP1rs26618(T/C) genotyping was performed using RT-PCR. Results: The frequency of the ACErs4291AA genotype was higher among the severe COVID-19 group than others (p < 0.001). The ERAP1rs26618TT genotype frequency was higher among the severe COVID-19 group in comparison with the mild group (p < 0.001) and non-infected controls (p = 0.0006). The frequency of the ACErs4291A allele was higher among severe COVID-19 than mild and non-infected groups (64.4% vs. 37.5%, and 34.4%, respectively), and the ERAP1rs26618T allele was also higher in the severe group (67.5% vs. 39.4%, and 49.4%). There was a statistically significant association between severe COVID-19 and ACErs4291A or ERAP1rs26618T alleles. The coexistence of ACErs4291A and ERAP1rs26618T alleles in the same individual increase the severity of the COVID-19 risk by seven times [OR (95%CI) (LL−UL) = 7.058 (3.752−13.277), p < 0.001). A logistic regression analysis revealed that age, male gender, non-vaccination, ACErs4291A, and ERAP1rs26618T alleles are independent risk factors for severe COVID-19. Conclusions: Persons carrying ACErs4291A and/or ERAP1rs26618T alleles are at higher risk of developing severe COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with coronavirus disease 2019 (COVID-19), but it is not clear whether this RNAemia reflects viremia (ie, virus particles) and how it relates to host immune responses and outcomes. METHODS: SARS-CoV-2 vRNA was quantified in plasma samples from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-intensive care unit [ICU]), and 23 ICU patients. vRNA levels were compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in plasma. RESULTS: SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6%, and 11.1% of ICU, non-ICU, and outpatients, respectively. Virions were detected in plasma pellets using electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (P < .0001); for inpatients, plasma vRNA levels were strongly associated with higher World Health Organization (WHO) score at admission (P = .01), maximum WHO score (P = .002), and discharge disposition (P = .004). A plasma vRNA level >6000 copies/mL was strongly associated with mortality (hazard ratio, 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (P < .01) but not with plasma neutralizing antibody titers (P = .8). CONCLUSIONS: Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia correlate strongly with disease severity, patient outcome, and specific inflammatory biomarkers but not with neutralizing antibody titers.

Definition of the Immune Parameters Related to COVID-19 Severity.

A relevant portion of patients with disease caused by the severe acute respiratory syndrome coronavirus 2 (COVID-19) experience negative outcome, and several laboratory tests have been proposed to predict disease severity. Among others, dramatic changes in peripheral blood cells have been described. We developed and validated a laboratory score solely based on blood cell parameters to predict survival in hospitalized COVID-19 patients. We retrospectively analyzed 1,619 blood cell count from 226 consecutively hospitalized COVID-19 patients to select parameters for inclusion in a laboratory score predicting severity of disease and survival. The score was derived from lymphocyte- and granulocyte-associated parameters and validated on a separate cohort of 140 consecutive COVID-19 patients. Using ROC curve analysis, a best cutoff for score of 30.6 was derived, which was associated to an overall 82.0% sensitivity (95% CI: 78-84) and 82.5% specificity (95% CI: 80-84) for detecting outcome. The scoring trend effectively separated survivor and non-survivor groups, starting 2 weeks before the end of the hospitalization period. Patients' score time points were also classified into mild, moderate, severe, and critical according to the symptomatic oxygen therapy administered. Fluctuations of the score should be recorded to highlight a favorable or unfortunate trend of the disease. The predictive score was found to reflect and anticipate the disease gravity, defined by the type of the oxygen support used, giving a proof of its clinical relevance. It offers a fast and reliable tool for supporting clinical decisions and, most important, triage in terms of not only prioritization but also allocation of limited medical resources, especially in the period when therapies are still symptomatic and many are under development. In fact, a prolonged and progressive increase of the score can suggest impaired chances of survival and/or an urgent need for intensive care unit admission.

Physiological health indexes predict deterioration and mortality in patients with COVID-19: a comparative study.

Old age is a crucial risk factor for severe coronavirus disease 2019 (COVID-19), with serious or fatal outcomes disproportionately affecting older adults compared with the rest of the population. We proposed that the physiological health status and biological age, beyond the chronological age itself, could be the driving trends affecting COVID-19 severity and mortality. A total of 155 participants hospitalized with confirmed COVID-19 aged 26-94 years were recruited for the study. Four different physiological summary indices were calculated: Klemera and Doubal's biological age, PhenoAge, physiological dysregulation (PD; globally and in specific systems), and integrated albunemia. All of these indices significantly predicted the risk of death (p < 0.01) after adjusting for chronological age and sex. In all models, men were 2.4-4.4-times more likely to die than women. The global PD was shown to be a good predictor of deterioration, with the odds of deterioration increasing by 41.7% per 0.5-unit increase in the global PD. As for death, the odds also increased by 68.3% per 0.5-unit increase in the global PD. Our results are partly attributed to common chronic diseases that aggravate COVID-19, but they also suggest that the underlying physiological state could capture vulnerability to severe COVID-19 and serve as a tool for prognosis that would, in turn, help inpatient management.

The Impact of SARS-CoV-2 Primary Vaccination in a Cohort of Patients Hospitalized for Acute COVID-19 during Delta Variant Predominance.

Vaccine breakthrough SARS-CoV-2 infections necessitating hospitalization have emerged as a relevant problem with longer time interval since vaccination and the predominance of the Delta variant. The aim of this study was to evaluate the association between primary vaccination with four SARS-CoV-2 vaccines authorized for use in the European Union-BNT162b2, ChAdOx-1S, mRNA-1273 or Ad.26.COV2.S-and progression to critically severe disease (mechanical ventilation or death) and duration of hospitalization among adult patients with PCR-confirmed acute COVID-19 hospitalized during the Delta variant predominance (October-November 2021) in Slovenia. Among the 529 enrolled patients hospitalized with COVID-19 (median age, 65 years; 58.2% men), 175 (33.1%) were fully vaccinated at the time of symptom onset. Compared with 345 unvaccinated patients, fully vaccinated patients with breakthrough infections were older, more often immunocompromised, and had higher Charlson comorbidity index scores. After adjusting for sex, age, and comorbidities, fully vaccinated patients had lower odds for progressing to critically severe disease and were discharged from the hospital earlier than unvaccinated patients. Vaccination against SARS-CoV-2 remains an extremely effective intervention to alleviate morbidity and mortality in COVID-19 patients.

People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden.

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in people critically ill with COVID-19. Here, we present high-dimensional profiling of blood and respiratory samples from people with severe COVID-19 to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNA sequencing (RNA-seq)-based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time lead to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2-infected myeloid cells in the lower respiratory tract upregulate CXCL10, leading to a higher risk of death. Our analysis suggests a pivotal role for viral-infected myeloid cells and protracted interferon signaling in severe COVID-19.

SARS-COV-2 Infection in Children and Red Blood Cell Distribution Width.

SARS-COV-2 infection due to Coronavirus is highly contagious and causes varying degrees of illness throughout the world. Recent literature has shown an association between red blood cell distribution width (RDW) and adverse outcomes among adult patients with COVID-19. Multiple hypotheses can explain the potential prognostic role of RDW in COVID-19 infection. The aim of this study is to describe RDW values in SARS-COV-2 infected children admitted to the Pediatric Emergency Department to shed light on the potential role of RDW as a prognostic factor in this specific group. Of 1086 tested children observed from March 2020 to April 2021, 36 positive SARS-COV-2 children (0-16 years) did not show clinically significant differences in RDW values according to illness categories, days of hospitalization, presence of multisystem inflammatory syndrome in children (MIS-C), or viral load (cycle threshold (CT) values). This study is the first to investigate this issue in a SARS-COV-2 infected pediatric population. Despite our negative results, given the high incidence of Delta variant in children, the low cost of the examination, its prognostic role described in adults, and its association to other pediatric illnesses, we believe that the role of RDW in SARS-COV-2 infected children should be deeper assessed and that larger collaborative studies on this issue are required.

Clinical and Laboratory Predictors of Mortality in COVID-19 Infection: A Retrospective Observational Study in a Tertiary Care Hospital of Eastern India.

Introduction COVID-19 is associated with huge morbidity and mortality in India. Identification of factors associated with mortality would make a difference in the management of COVID-19 infection-related illness. Objective To assess clinical & laboratory parameters associated with adverse outcomes among 984 patients with COVID-19 infection admitted to a tertiary care hospital in eastern India. Materials and methods All patients with real-time polymerase chain reaction (RTPCR) or rapid antigen positive for COVID-19 admitted at our All India Institute of Medical Sciences (AIIMS) Patna between 1st July to 30th Aug 2020 were included for analysis. Statistical analysis was performed using Stata, version 10 (Stata Corp, College Station, USA). Four subgroup regression models have been analyzed to predict the odds of death. Results A total of 984 COVID-19 cases admitted to our hospital during the given period were analyzed. Out of 984 cases, 762 (77.44%) were males and 222 (22.56%) females. The overall case-fatality rate among admitted cases was 254 (25.81%) [males (26.64%) and females (22.96%)]. The final logistic regression model showed that patients presenting with severe COVID-19 disease (adjusted odds ratio [aOR]: 17.81), cough (aOR: 3.83), dyspnea (aOR:2.35), age 60-75 (aOR:1.47), age >75 years (aOR:3.97), presence of chronic kidney disease (CKD) (aOR:2.95), were found to be significantly associated with a high risk of mortality after controlling for the confounders (p<0.05). Among lab variable, total leukocyte count (TLC) (>10,000/mm3) (aOR: 1.74), neutrophil-lymphocyte ratio (NLR) (>3.3) (aOR:2.37), serum albumin (<3.4 g/dl) (aOR : 2.3), blood urea (>43 gm/dl) (aOR:3.72), ferritin (>322) (aOR:2.39), and D-dimer (>0.5) (aOR:5.58) were significantly associated with higher mortality (p<0.05) Conclusion Age 60 years plus, presence of CKD, and severe covid infection carried the highest risk of mortality. Lab markers such as raised TLC, ferritin, D-dimer, and low albumin were associated with worse outcomes in our subset of COVID-19-related illness.

The prognostic value of serial troponin measurements in patients admitted for COVID-19.

AIMS: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact. METHODS AND RESULTS: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035). CONCLUSIONS: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

Asthma in a large COVID-19 cohort: Prevalence, features, and determinants of COVID-19 disease severity.

BACKGROUND: Asthma prevalence among COVID-19 patients seems to be surprisingly low. However the clinical profile of COVID-19 asthmatic patients and potential determinants of higher susceptibility/worse outcome have been scarcely investigated. We aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity. METHODS: Medical records of patients admitted to COVID-Units of six Italian cities major hospitals were reviewed. Demographic and clinical data were analyzed and compared according to the COVID-19 outcome (death/need for ventilation vs discharge at home without requiring invasive procedures). RESULTS: Within the COVID-Units population (n = 2000) asthma prevalence was 2.1%. Among the asthmatics the mean age was 61.1 years and 60% were females. Around half of patients were atopic, blood eosinophilia was normal in most of patients. An asthma exacerbation in the 6 months before the Covid-Unit admittance was reported by 18% of patients. 24% suffered from GINA step 4-5 asthma, and 5% were under biologic treatment. 31% of patients were not on regular treatment and a negligible use of oral steroid was recorded. Within the worse outcome group, a prevalence of males was detected (64 vs 29%, p = 0.026); they suffered from more severe asthma (43 vs 14%, p = 0.040) and were more frequently current or former smokers (62 vs 25%, p = 0.038). CONCLUSIONS: Our report, the first including a large COVID-19 hospitalized Italian population, confirms the low prevalence of asthma. On the other side patients with GINA 4/5 asthma, and those not adequately treated, should be considered at higher risk.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection.

Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739-7.995), p = 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio > 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation.