Photodegradation of Rituximab and Critical Evaluation of Its Sensibility to Electromagnetic Radiation.

Rituximab is a monoclonal antibody used in the treatment of lymphoma non-Hodgkin. This mAb is photosensitive as it is administrated to the patient by infusion/perfusion; therefore, photostability is a decisive factor in the efficacy of this biologic. To better understand the photodegradation mechanisms of Rituximab, this biologic was exposed to different irradiance conditions. We show in this study that this mAb photodegrade proportionally to irradiance intensities. The main modifications of Rituximab by irradiance correlate to the increase in aggregates, decrease in its Tm, acidic charge variants, oxidation of the Trp (36) in the heavy chain, and decrease in complement-dependent cytotoxicity (CDC) potency. To understand the relationship between real-life photo-exposition conditions and ICH standardized light tests, a full characterization was set up. Worst photo-stress cases were evaluated, 1 and 2 h under direct sunlight through a window, mimicking the ID65 electromagnetic radiation profile. Our results show that only exposition to direct sun irradiance during 2 h, (≈ 150 kluxes•h), increases critically soluble and insoluble aggregates, diminishing Tm, increasing acidic charge variants, and the photooxidation of the Trp (36) in the heavy chain measured by peptide mapping-RP-UPLC-MS. A decrease in CDC below 80% resulted under this condition, which correlates with physicochemical analyses. While inside light-room exposition (similar to ICH test) and ICH conditions do not have any contribution to the degradation of Rituximab measured by these physicochemical and biological analytical methods. These results indicate that exposition of Rituximab to below ≈ 75 kluxes•h of sun light cannot photodegrade critically this biologic inside of its primary container.

Hypodermic needle fixation without fluoroscopy versus k-wire fixation with fluoroscopy for distal phalangeal fractures: a comparative study.

BACKGROUND: Distal phalanx fractures are frequently encountered in our daily practice. They are often caused by crush injuries and are the most frequent work-related hand fractures. Different types of fixation have been proposed for displaced fractures. METHODS: A retrospective study was performed on two fixation types. Twenty-four distal phalanx fractures were treated with k-wire fixation with fluoroscopic control in a main operating room setting. Twenty-five distal phalanx fractures were treated with hypodermic needle fixation without fluoroscopic control in an emergency treatment room setting. Clinical and radiological data were collected on fracture type, fracture healing and complications. The cost of both types of surgery was assessed. RESULTS: No significant difference in healing time, union, delayed union and non-union was found between the two groups. Loosening was significantly more frequent in the hypodermic needle group, without affecting clinical or radiographic outcome. No infections were encountered in both groups. Surgery performed in the emergency treatment room reduced the cost with 9000 dollars when compared to surgery performed the main operating room. CONCLUSION: Treatment of displaced distal phalanx fractures with hypodermic needle fixation yields good results. Performing this procedure in a treatment room is safe and might reduce operative time, institutional costs and radiation exposure for both surgeon and patients.

Detection and quantification of leached ethylene glycol in biopharmaceuticals by RP-UHPLC.

Biopharmaceuticals are in direct contact with different plastic materials, which can contribute to process-related impurities. Polyethylene terephthalate glycol (PETG) is used for storage and transportation of biopharmaceuticals and it is synthetized from the poly-condensation reaction between ethylene glycol, 1,4-cyclodimethanol and dimethyl terephthalate. PETG bottles are analyzed for such impurities prior to release; however, the nature of the pharmaceutical matrix can extract impurities, so it is important to measure these contaminants in biopharmaceuticals. This study shows a liquid chromatography method for the quantification of ethylene glycol in PETG materials as an alternative to the standard USP colorimetric method. The method is based on the derivatization of ethylene glycol with benzoyl chloride in a Schotten-Baumann reaction. We present a comprehensive method development and validation. The method allows the detection and quantification of leached and extracted ethylene glycol directly in biopharmaceuticals after years of storage in contact with PETG bottles. Results showed residual ethylene glycol in drug substances to a level of ≈  0.1-0.5 µg/mL exposed during 2-6 years of storage in PETG bottles and ≈ 0.2-0.9 µg/mL in biopharmaceuticals. Graphical abstract Biopharmaceuticals must be free or low concentration for leachables, FR-UHPLC-UV analysis is a precise and accurate analytical method for ethylene glycol measurement. This leachable is commonly present in products in direct contact with PETG plastic.

Correction to: The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart.

The article "The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart".

Confirmation of the Cardioprotective Effect of MitoGamide in the Diabetic Heart.

PURPOSE: HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide. METHODS AND RESULTS: A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls. Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group. CONCLUSION: Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.

Furosemide stress test and interstitial fibrosis in kidney biopsies in chronic kidney disease.

BACKGROUND: Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST. METHODS: This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation. RESULTS: The mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed. CONCLUSIONS: Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02417883.

The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart.

PURPOSE: Methylglyoxal, a by-product of glycolysis and a precursor in the formation of advanced glycation end-products, is significantly elevated in the diabetic myocardium. Therefore, we sought to investigate the mitochondria-targeted methylglyoxal scavenger, MitoGamide, in an experimental model of spontaneous diabetic cardiomyopathy. METHODS: Male 6-week-old Akita or wild type mice received daily oral gavage of MitoGamide or vehicle for 10 weeks. Several morphological and systemic parameters were assessed, as well as cardiac function by echocardiography. RESULTS: Akita mice were smaller in size than wild type counterparts in terms of body weight and tibial length. Akita mice exhibited elevated blood glucose and glycated haemoglobin. Total heart and individual ventricles were all smaller in Akita mice. None of the aforementioned parameters was impacted by MitoGamide treatment. Echocardiographic analysis confirmed that cardiac dimensions were smaller in Akita hearts. Diastolic dysfunction was evident in Akita mice, and notably, MitoGamide treatment preferentially improved several of these markers, including e'/a' ratio and E/e' ratio. CONCLUSIONS: Our findings suggest that MitoGamide, a novel mitochondria-targeted approach, offers cardioprotection in experimental diabetes and therefore may offer therapeutic potential for the treatment of cardiomyopathy in patients with diabetes.

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia.

Nanoparticles for Protein Sensing in Primary Containers: Interaction Analysis and Application.

Silver nanoparticles (AgNPs) are known to interact with proteins, leading to modifications of the plasmonic absorption that can be used to monitor this interaction, entailing a promising application for sensing adsorption of therapeutic proteins in primary containers. First, transmission electron microscopy in combination with plasmonic absorption and light scattering responses were used to characterize AgNPs and protein-AgNP complexes, including its concentration dependence, using two therapeutic molecules as models: a monoclonal antibody (mAb) and a synthetic copolymer (SC). Upon interaction, a protein corona was formed around AgNPs with the consequent shifting and broadening of their characteristic surface plasmon resonance (SPR) band (400 nm) to 410 nm and longer wavelenghts. Additional studies revealed secondary and three-dimensional structure modifications of model proteins upon interaction with AgNPs by circular dichroism and fluorescence techniques, respectively. Based on the modification of the SPR condition of AgNPs upon interaction with proteins, we developed a novel protein-sensing application of AgNPs in primary containers. This strategy was used to conduct a compatibility assessment of model proteins towards five commercially available prefillable glass syringe (PFS) models. mAb- and SC-exposed PFSs showed that 74 and 94% of cases were positive for protein adsorption, respectively. Interestingly, protein adsorption on 15% of total tested PFSs was negligible (below the nanogram level). Our results highlight the need of a case-by-case compatibility assessment of therapeutic proteins and their primary containers. This strategy has the potential to be easily applied on other containers and implemented during early-stage product development by pharmaceutical companies and for routine use during batch release by packaging manufacturers.

Mammalophilic feeding behaviour of Culex quinquefasciatus mosquitoes collected in the cities of Chetumal and Cancun, Yucatán Peninsula, Mexico.

OBJECTIVE: The studie describes the blood-feeding behaviour of mosquitoes in Mexico, to understand host-vector relationships and dynamics of disease transmission. METHODS: From September 2012 to November 2012 and in November 2013, 911 blood-fed Cx. quinquefasciatus mosquitoes were collected with aspirators inside houses in Chetumal and Cancun. Blood meals were analysed by PCR and subsequent Sanger sequencing of the cytochrome b gene. RESULTS: 93.3% of mosquitoes fed on mammals, 6.5% on birds and 0.2% on reptiles. The most frequent vertebrate hosts were humans (65.4%), dogs (23.2%), chicken (5.4%), cattle (2.2%) and cats (1.8%). CONCLUSIONS: Cx. quinquefasciatus most frequently fed on humans and dogs in both studied cities, which is in contrast to a previous study that demonstrated lower prevalence of mammalian blood in engorged Cx. quinquefasciatus.

Analysis of therapeutic proteins and peptides using multiangle light scattering coupled to ultra high performance liquid chromatography.

Analysis of the physical properties of biotherapeutic proteins is crucial throughout all the stages of their lifecycle. Herein, we used size-exclusion ultra high performance liquid chromatography coupled to multiangle light scattering and refractive index detection systems to determine the molar mass, mass-average molar mass, molar-mass dispersity and hydrodynamic radius of two monoclonal antibodies (rituximab and trastuzumab), a fusion protein (etanercept), and a synthetic copolymer (glatiramer acetate) employed as models. A customized instrument configuration was set to diminish band-broadening effects and enhance sensitivity throughout detectors. The customized configuration showed a performance improvement with respect to the high-performance liquid chromatography standard configuration, as observed by a 3 h column conditioning and a higher resolution analysis in 20 min. Analysis of the two monoclonal antibodies showed averaged values of 148.0 kDa for mass-average molar mass and 5.4 nm for hydrodynamic radius, whereas for etanercept these values were 124.2 kDa and 6.9 nm, respectively. Molar-mass dispersity was 1.000 on average for these proteins. Regarding glatiramer acetate, a molar mass range from 3 to 45 kDa and a molar-mass dispersity of 1.304 were consistent with its intrinsic peptide diversity, and its mass-average molar mass was 10.4 kDa. Overall, this method demonstrated an accurate determination of molar mass, overcoming the difficulties of size-exclusion chromatography.

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD).

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

Upper body thermal images and associated clinical data from a pilot cohort study of COVID-19.

OBJECTIVES: The data was collected for a cohort study to assess the capability of thermal videos in the detection of SARS-CoV-2. Using this data, a published study applied machine learning to analyze thermal image features for Covid-19 detection. DATA DESCRIPTION: The study recorded a set of measurements from 252 participants over 18 years of age requesting a SARS-CoV-2 PCR (polymerase chain reaction) test at the Hospital Zambrano-Hellion in Nuevo León, México. Data for PCR results, demographics, vital signs, food intake, activities and lifestyle factors, recently taken medications, respiratory and general symptoms, and a thermal video session where the volunteers performed a simple breath-hold in four different positions were collected. Vital signs recorded include axillary temperature, blood pressure, heart rate, and oxygen saturation. Each thermal video is split into 4 scenes, corresponding to front, back, left and right sides, and is available in MPEG-4 format to facilitate inclusion into pipelines for image processing. Raw JPEG images of the background between subjects are included to register variations in room temperatures.

Capillary gel electrophoresis for the quantification and purity determination of recombinant proteins in inclusion bodies.

In this work, a high-resolution CGE method for quantification and purity determination of recombinant proteins was developed, involving a single-component inclusion bodies (IBs) solubilization solution. Different recombinant proteins expressed as IBs were used to show method capabilities, using recombinant interferon-ß 1b as the model protein for method validation. Method linearity was verified in the range from 0.05 to 0.40 mg/mL and a determination coefficient (r(2) ) of 0.99 was obtained. The LOQs and LODs were 0.018 and 0.006 mg/mL, respectively. RSD for protein content repeatability test was 2.29%. In addition, RSD for protein purity repeatability test was 4.24%. Method accuracy was higher than 90%. Specificity was confirmed, as the method was able to separate recombinant interferon-ß 1b monomer from other aggregates and impurities. Sample content and purity was demonstrated to be stable for up to 48 h. Overall, this method is suitable for the analysis of recombinant proteins in IBs according to the attributes established on the International Conference for Harmonization guidelines.

Analysis of recombinant monoclonal antibodies by capillary zone electrophoresis.

Analytical platforms that characterize charge heterogeneity in therapeutic proteins, such as mAbs, are important tools that can be used to define quality attributes. CZE separates protein moieties close to their native state and is a valuable physicochemical analytical method that can be used in parallel with other orthogonal methods for characterization and comparability. In this study, custom conditions for the analysis of charge heterogeneity of two mAbs were developed with regard to critical parameters in the BGE, running conditions, and sample treatment. The method application was tested for up to four mAbs and one mAb fragment. The electropherograms showed specific profiles and contrasting levels of basic and acidic isoforms with respect to the main isoform. Issues that surround this method, such as peak tailing and capillary lifetime, are summarized. Using this method, the identities of rituximab and trastuzumab were confirmed, based on the correspondence between the biosimilars and reference products, noninterference of the sample matrix, and the ability to separate spiked samples of related mAbs. The RSD of the isoform content and migration time for the method repeatability were less than 2 and 1%, respectively.

Molecular and Serological Identification of Anaplasma marginale and Borrelia burgdorferi in Cattle and Ticks from Nuevo Leon, Northern Mexico.

Ticks and tick-borne diseases affect livestock productivity and cause significant economic losses. Therefore, surveillance of these pathogens and vectors is paramount to reducing these effects in livestock. This study aimed to identify Anaplasma marginale and Borrelia burgdorferi sensu lato in ticks collected from cattle. Molecular biology techniques were utilized to identify A. marginale for both types of samples, i.e., ticks and bovine blood. Serology of cattle using indirect immunofluorescence assay (IFA) was conducted to determine antibodies to B. burgdorferi s.l. from seven locations in Nuevo Leon, Mexico, between 2015 and 2017. From 404 bovines, 2880 ticks were collected: Rhipicephalus microplus (2391 females and 395 males), Amblyomma spp. (51 females and 42 males) and Dermacentor variabilis (1 female). Rhipicephalus microplus represented the largest specimens captured, with 96.7% within the seven study sites. PCR processed only 15% (442) of tick samples to identify A. marginale. Field genera proportions were followed to select testing tick numbers. Results showed that 9.9% (44/442) of A. maginale infected the pooled tick species, whereas the highest percent corresponded to 9.4% (38/404) in R. microplus. Regarding the molecular analysis of blood samples, 214 of 337 (63.5%) were positive for A. maginale. In each of the seven locations, at least one bovine sample tested positive for A. maginale. Borrelia burgdorferi s.l. was not found either in the ticks or serum samples. Two A.marginale DNA nucleotide sequences obtained in this study were deposited in the GenBank with the following accession numbers OR050501 cattle, and OR050500 R.microplus tick. Results of this work point to current distribution of bovine anaplasmosis in northern Mexico.

Immunomodulatory activity of diethylcarbamazine on humoral, cellular cytokine response and respiratory burst in BALB/c mice.

Diethylcarbamazine (DEC) is an anthelmintic piperazine derivative drug with putative immunomodulating properties, including increased platelet and granulocyte adhesion to parasites and enhanced production of cytokines. To further analyse these properties in a well-established animal model, we evaluated the effect of DEC on antibody, cellular cytokine response and respiratory burst in BALB/c mice. Animals were challenged with a thymus-dependent (tetanus toxoid, (TT)) and with a thymus-independent (lipopolysaccharide, (LPS)) antigen and treated with DEC for seven days with two different doses (50 mg/day and 500 mg/day). Serum was assessed for antibody production at 0, 4, 7, 14, 21 and 28 days after stimulation and at 0, 24 and 48 h for IL-2, IFN-γ, IL-10 and IL-12 release. Respiratory burst of neutrophils and monocytes from peripheral blood was measured by flow cytometry. We found low-dose treatment with DEC enhanced cytokine production vs. TT and antibody production vs. LPS, whereas a higher dose enhanced significantly the respiratory burst of both polymorphonuclear leukocytes and monocytes, with a significant higher effect on the former. Our results suggest a stimulating, dose-dependent immunomodulatory effect of DEC with a higher effect on the phagocytic cells.

Diethylcarbamazine as potential treatment of COVID-19 lung fibrosis.

Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect.

A smart school routing and scheduling problem for the new normalcy.

One of the critical actions that emerged during the onset of the New Normalcy after COVID-19 lockdowns, is the safe return to schools and workplaces. Therefore, dedicated transportation services need to adapt to meet new requirements such as arrival reliability for multiple bell times, the consequent staggering of arrivals and departures, and the decrease in bus capacity due to the physical distancing required by regulators. In this work, we address these issues plus additional labor conditions concerning drivers for a university context; with the goal of optimizing social interests such as covering demand and travel time under limited resources. We propose a bi-level approach, where firstly a bus routing generation sub-problem is solved before a bus scheduling sub-problem. This (strategic) solution is then considered as the baseline for subsequent dynamic (operational) routing. The latter is based on real-time demand provided by the students via a mobile app and considers stop-skipping to further minimize travel time. This integrated transport solution was tested in a university case, showing that with the same resources, it can meet these new requirements. In addition, numerical experimentation was also carried out with benchmark instances to identify, among available and literature-recommended solution algorithms and an effective tailored Tabu Search implementation, those that perform best for this type of problems.

Early increase of serum ferritin among COVID-19 patients is associated with need of invasive mechanical ventilation and with in-hospital death.

BACKGROUND: COVID-19 may trigger an acute hyperinflammatory syndrome characterised by heightened levels of acute phase reactants and is associated with adverse outcomes among hospitalised individuals. The relationship between 48-hour changes in acute phase reactants and adverse outcomes is unclear. This study evaluated the relationship between change in four acute phase reactants (interleukin-6, procalcitonin, ferritin, and C-reactive protein), and the risk for in-hospital death and invasive mechanical ventilation. METHODS: A retrospective cohort among 2,523 adult patients hospitalised with COVID-19 pneumonia was conducted. Changes in IL-6, procalcitonin, ferritin, and CRP from admission to 48 h after admission were recorded. Delta was calculated using the difference in each acute phase reactant at admission and at 48-hours. Delta in acute phase reactants and the risk for in-hospital death and invasive mechanical ventilation was assessed using logistic regression models adjusting for demographics and comorbidities. RESULTS: Patients with both admission and 48-hour measurement for interleukin-6 (IL-6) (n = 541), procalcitonin (n = 828), ferritin (n = 1022), and C-reactive protein (CRP) (n = 1919) were included. Baseline characteristics were similar across all four populations. Increases in ferritin associated with a heightened risk of in-hospital death (OR 1.00032; 95%CI 1.00007- 1.00056; p < .001) and invasive mechanical ventilation (OR 1.00035; 95%CI 1.00014- 1.00055; p = .001). Therefore, for every 100 ng/mL increase in ferritin, the odds for in-hospital death and invasive mechanical ventilation increase by 3.2% and 3.5%, respectively. CONCLUSIONS: Delta in ferritin is associated with in-hospital death and invasive mechanical ventilation. Other acute phase reactants were not associated with these outcomes among COVID-19 inpatients.