COVID-19 Patients Research Articles

COVID-19 patients putting on the brakes with PAR1 autoantibodies.

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Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19

Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated the new-onset autoantibody repertoire in 525 healthcare workers and hospitalized COVID-19 patients at five time points over a 16-month period in 2020 and 2021 using proteome-wide and targeted protein and peptide arrays. Our results show that prevalent new-onset autoantibodies against a wide range of antigens emerged following SARS-CoV-2 infection in relation to pre-infectious baseline samples and remained elevated for at least 12 months. We found an increased prevalence of new-onset autoantibodies after severe COVID-19 and demonstrated associations between distinct new-onset autoantibodies and neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined the main epitopes of selected new-onset autoantibodies, validated them in independent cohorts of neuro-COVID and pre-pandemic healthy controls, and identified sequence similarities suggestive of molecular mimicry between main epitopes and the conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein. Our work describes the complexity and dynamics of the autoantibody repertoire emerging with COVID-19 and supports the need for continued analysis of the new-onset autoantibody repertoire to elucidate the mechanisms of the post-COVID-19 condition.

A pooled analysis of the incidence and mortality risk of atrial fibrillation in patients with COVID-19.

There exist serious cardiovascular complications subsequent to SARS-Cov2 infection (COVID-19); however, the association between COVID-19 and atrial fibrillation (AF) remains to be elucidated. We aimed to assess the prevalence of AF among COVID-19 patients and its associated risk of death. The present systematic review was performed in accordance with the PRISMA guidelines. The protocol was registered with CRD42022306523. A comprehensive literature search was performed across PubMed, Embase, and Cochrane databases to identify studies reporting on the prevalence of pre-existing or new-onset fibrillation (AF), and/or the associated clinical outcomes in patients with COVID-19 from January 2020 to December 2023. The random-effect model was used to estimate the prevalence of AF and its related mortality. A total of 80 studies, including 39,062,868 COVID-19 patients, were identified in the present investigation. The prevalence rates of pre-existing AF or new-onset AF were 10.5% (95% CI [9.3-11.7%]) or 10.3% (95% CI [6.2-14.5%]), respectively. Subgroup analysis revealed a two fold higher incidence of AF in older patients (≥65 years) compared to younger patients (<65 years) (14.4% vs. 6.4%). The highest rate of AF was observed in Europeans (10.7%, 95% CI [10.2-11.2%]), followed by Northern Americans (10.0%, 95% CI [8.2-11.7%]), while Asians demonstrated a lower prevalence (2.7%, 95% CI [2.2-3.3%]). Notably, severe COVID-19 patients displayed a significantly elevated prevalence of AF at 14.l% (95% CI [13.3-14.9%]), which was approximately 2.5-fold higher than that in non-severe patients (5.2%, 95% CI [4.8-5.5%]). Both pre-existing (HR: 1.83, 95% CI [1.49-2.17]) and new-onset AF (HR: 3.47, 95% CI [2.26-5.33]) were associated with an increased mortality risk among COVID-19 patients. Furthermore, the effect on mortality risk was more significant in Asians (HR: 5.33, 95% CI [1.62-9.04]), compared to Europeans (HR: 1.68, 95% CI [1.24-2.13]) and North Americans (HR: 2.01, 95% CI [1.18-2.83]). This study comprehensively investigated the association between AF and COVID-19 in a real-world setting. Notably, a high prevalence of AF was observed among older individuals, severe COVID-19 patients, and in Europe and Northern America. Moreover, co-existing AF was found to be associated with an increased risk for mortality. Further investigations are warranted to improve the management and outcomes of COVID-19 patients with AF.

The presence of yeasts and bacteria in free-living amoebae isolated from COVID-19 patients: concern for secondary infections

ABSTRACT This study aimed to investigate the presence of SARS-CoV-2, yeasts, and bacteria in isolated free-living amoeba (FLA) from COVID-19 patients. Nasopharyngeal swabs (n = 60) were obtained from COVID-19 patients. After cultivation, morphological characterization, and RNA/DNA extraction, the presence of selected microorganisms was investigated. From 60 COVID-19 samples, 18 (30%) were positive for FLA. Acanthamoeba sp. Naegleria australiensis, Tetramitus sp. and Vermamoeba vermiformis were characterized in 12 (80%), 1 (6.66%), 2 (13.33%), and 7 (38.88%) of samples, respectively. SARS-CoV-2 RNA was not detected in FLA. Candida albicans, C. tropicalis, and C. parapsilosis were detected in (11/18; 61.11%), (3/18; 16.67%), and (3/18; 16.67%) of samples, respectively. Geotrichum candidum was detected in 10/18 (55.55%) of samples. Streptococcus spp. and Staphylococcus spp. were identified in 16/18 (88.88%) and 3/18 (16.67%), respectively. The presence of yeasts and bacteria signifies the possible role of FLA in distribution of secondary infections in susceptible patients.

The Relationship between Plasminogen Activator Inhibitors and the Severity of COVID-19

The fibrinolysis process is assisted by plasminogen activators and inhibitors by converting plasminogen into plasmin, which later will promote the fibrinolysis process. Incomplete fibrinolysis increases the risk of thrombosis in patients with COVID-19. Plasminogen Activator Inhibitor (PAI-1) plays an important role as acute phase reactants to be used as a marker to assess the prognosis and mortality of COVID-19 patients. This study aimed to elaborate on whether fibrinolysis shutdown occurs in COVID-19 patients using PAI-1 as a marker of fibrinolysis. This was a cross-sectional analytical study from November 2022 to May 2023. This research consisted of a total of 39 patients with COVID-19, hospitalized at Haji Adam Malik General Hospital, Medan. PAI-test in COVID-19 patients was carried out with the ELISA method using Chemwell Analyzer. The severity of COVID-19 measured by clinical examination was divided into moderate, severe, and critical. The association between the two variables was subjected to a comparative test followed by a correlation test to explore the association between the two variables with an independent T-test. In this study, the median PAI-1 level was 1.77 ng/mL (0.71–11.49 ng/mL). The highest PAI-1 levels were observed in the critical severity group, followed by the severe and moderate group of 8.54 ng/mL (5.76–10.84), 2.45 ng/mL (0.71–11.49), and 1.29 ng/mL (0.73–3.77), respectively. There was a significant relationship between PAI-1 levels and the severity of COVID-19 patients (p=0.003). PAI-1 cut-off value of 1.89 ng/mL may predict the degree of COVID-19 severity with sensitivity of 88.9%, specificity of 90.5%, and accuracy of 89.7%. This study classified the severity of COVID-19 into two categories, which are moderate (n=21) and severe-critical (n=18) to obtain the AUC value of PAI-1. PAI-1 can be used to predict the severity of COVID-19 disease with a moderate level (AUC &gt;70–80%). This phenomenon can be secondary to enhanced platelet aggregation, inflammation micro thrombosis, and impaired fibrinolysis. Fibrinolysis disorders lead to a fibrin buildup and increased levels of PAI-1 in the circulation.

Prevalence and Association of Deep Vein Thrombosis on Clinical Outcomes Among COVID-19 Patients

Background Studies have shown that COVID-19 could lead coagulation defects, resulting in increased morbidity and mortality. In this study, we sought to estimate the prevalence of deep vein thrombosis (DVT) among COVID-19 hospitalizations and its effects on hospital outcomes using a large administrative database. Methods We conducted a retrospective analysis of the 2020 California State Inpatient Database. All hospitalizations ≥18 years and primary diagnosis of COVID-19 were included and were stratified into those with and without DVT. The main outcomes of the study were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit admission. Results We included a total of 94,114 primary COVID-19 hospitalizations for the analysis. Among them, 1575 (1.7%) had DVT. After adjusting for covariates, regression analysis showed that those with DVT had significantly greater odds for mortality (adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 2.07–2.65), prolonged length of stay (aOR, 3.51; 95% CI, 3.16–3.91), vasopressor use (aOR, 4.23; 95% CI, 3.78–4.74), mechanical ventilation (aOR, 2.90; 95% CI, 2.38–3.53), and intensive care unit admission (aOR, 4.32; 95% CI, 3.85–4.84). Conclusions In our cohort, though only a few COVID-19 hospitalizations had DVT, the risk for adverse outcome was significantly higher. Therefore, healthcare providers should promptly monitor for DVT among COVID-19 patients and manage it promptly.

The Correlation between Interleukin-6 and D-dimer in Severe and Critical COVID-19 Patients

Severe and critical COVID-19 patients are known to experience hyperinflammatory conditions and endothelial damage primarily characterized by increased levels of IL-6 and D-dimer. This group of patients is also considered at risk of experiencing hemostasis disorders including decreased platelet counts, prolonged PT and APTT, as well as increased fibrinogen. Therefore, this study aimed to determine the correlation between IL-6 and D-dimer in severe and critical COVID-19 patients. The relationship between IL-6 and other hemostasis parameters such as platelet count, PT, APTT, and fibrinogen were also analyzed. A descriptive-correlative observational design was used with a retrospective cross-sectional approach. The subjects were severe and critical COVID-19 patients at Hasan Sadikin Hospital, Bandung treated between January to December 2021 and met the inclusion and exclusion criteria. Secondary data were taken from medical records and the Laboratory Information System (LIS). Correlation analysis between IL-6 and D-dimer as well as hemostasis parameters was carried out using the Spearman test. The results showed that among the total 167 subjects, the median age was 60 years. The number of male subjects was 110 (65.86%), while the most common comorbidity was hypertension (45.51%). The analysis showed a very weak and insignificant correlation between IL-6 and platelets (r= -0.044; p=0.571), IL-6 and PT (r=0.115; p=0.137), IL-6 and APTT (r=0.109; p=0.159), as well as IL-6 and fibrinogen (r= -0.087; p=0.264). However, the correlation between IL-6 and D-dimer was significant (r= 0.199; p=0.010). Interleukin-6 did not correlate with hemostasis parameters but correlated with D-dimer. This means that IL-6 and D-dimer may provide information about the inflammatory response in COVID-19 patients and help monitor disease progression.

Clinically Guided Adaptive Machine Learning Update Strategies for Predicting Severe COVID-19 Outcomes

Background: Machine learning algorithms are essential for predicting severe outcomes during public health crises like COVID-19. However, the dynamic nature of diseases requires continual evaluation and updating of these algorithms. This study aims to compare three update strategies for predicting severe COVID-19 outcomes post-diagnosis: 'naive' (a single initial model), 'frequent' (periodic retraining), and 'context-driven' (retraining informed by clinical insights). The goal is to determine the most effective timing and approach for adapting algorithms to evolving disease dynamics and emerging data. Methods: A dataset of 1.11 million COVID-19 patients from diverse U.S. regions was used to develop and validate an XGBoost algorithm for predicting severe outcomes upon diagnosis. Data included patient demographics, vital signs, comorbidities, and immunity-related factors (prior infection and vaccination status) from January 2007 to November 2021. The study analyzed the performance of the three update strategies from March 2020 to November 2021. Results: Predictive features changed over the pandemic, with comorbidities and vitals being significant initially, and geography, demographics, and immunity-related variables gaining importance later. The 'naive' strategy had an average AUC of 0.77, the 'frequent' strategy-maintained stability with an average AUC of 0.81, and the 'context-driven' strategy averaged an AUC of 0.80, outperforming the 'naive' strategy and aligning closely with the 'frequent' strategy. Conclusion: A context-driven approach, guided by clinical insights, can enhance predictive performance and offer cost-effective solutions for dynamic public health challenges. These findings have significant implications for efficiently managing healthcare resources during evolving disease outbreaks.

Impact of FCGR2A rs1801274 and IL-6R rs2228145 polymorphisms on tocilizumab response in the Iranian population with severe COVID-19

BackgroundAlthough several genetic biomarkers have been reported in the tocilizumab (TCZ) response in rheumatoid arthritis, no studies have addressed the pharmacogenomics effect of TCZ in COVID-19.MethodsIn this prospective longitudinal study, 95 individuals with severe COVID-19 were selected between 2020–2022. The recovery process was measured at 24 h, 48 h, and 10 days before and after taking TCZ. All participants were genotyped using RFLP-PCR. Different genotypes of FCGR2A rs1801274 and IL-6R rs2228145 were compared in terms of the recovery process.Results43.2% of patients were male and 56.8% were female with an average age of 58.20(± 16.214) years. The GA genotype for FCGR2A rs1801274 increased the risk of death (OR = 2.83, P = 0.038) and ventilation (OR = 2.71, P = 0.047) in TCZ-treated individuals. However, there was no risk of death and ventilation with IL-6R rs2228145 (P > 0.05). Additionally, docking analysis showed that not only IL6R but also FCGR2A can be a ligand for TCZ.ConclusionThis study provides valuable insights into the impact of genetic variations on the response rate of TCZ in COVID-19 patients. The GA genotype for FCGR2A rs1801274 was associated with poor treatment outcomes.

Multimorbidity raises the odds of decease in COVID-19 patients: An Iranian prospective study

Introduction: The prevalence of noncommunicable diseases is high in Iran. We postulated that multimorbidity may affect the rate of mortality from COVID-19. So, we investigated the relationship between multimorbidity and COVID-19 mortality. Methods: We used medical reports for collecting clinical laboratory data of patients with COVID-19 in this prospective investigation. Moreover, we documented whether the patient had a known diagnosis of different comorbidities. The patients with more than one comorbidity were considered multimorbidity. The length of follow-up was till participants were discharged from the hospital or deceased. The main outcome was to evaluate the relationship between multimorbidity and death in COVID-19 hospitalized patients. Results: The present prospective study included 1842 patients with COVID-19 with a multimorbidity rate of 37.40%. About 24.6% of participants with more than four comorbidities died. However, this value was about 17% in participants with less than four comorbidities. The odds of mortality from COVID-19 were 53% greater in patients with diabetes. Also, the odds of death were 2.05 (1.21, 3.45) times greater in patients with comorbidities≥4. Conclusion: The results indicated a high rate of multimorbidity in patients with COVID-19 which is related to a higher death rate. So, in countries with higher multimorbidity rates such as Iran, it is necessary to design efficient approaches to alleviate the spread of COVID-19.

The effect of corticosteroids in developing active pulmonary tuberculosis among patients with COVID-19.

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2-4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease.

Investigating TCR-pMHC interactions for TCRs without identified epitopes by constructing a computational pipeline

The molecular mechanisms underlying epitope recognition by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a computational pipeline that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms for TCRs without identified epitopes. By antigen specificity clustering, we mapped the epitope sequences between epitope-known and epitope-unknown TCRs from COVID-19 patients. One reported SARS-CoV-2 epitope, NQKLIANQF (S919–927), was identified for a TCR expressed by 614 T cells (TCR-614). Epitope screening also identified a potential cross-reactive epitope, KLKTLVATA (NSP31790–1798), for a TCR expressed by 204 T cells (TCR-204). By molecular dynamics (MD) simulations, we revealed the detailed epitope-recognition mechanisms for both TCRs. The structural motifs responsible for epitope recognition revealed by the MD simulations are consistent with the sequential features recognized by the sequence-based clustering method. We hope that this strategy could facilitate the discovery and optimization of TCR-based therapeutics.

A Descriptive Analysis of the Use of Various Therapeutics in a Cohort of COVID-19 Patients and the Influence of Media Coverage

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the healthcare system immensely throughout 2020-2022. Treatment practices varied in Texas, as guidelines were in flux. As a result, a variety of therapeutics were used. Many verified medications with scientific basis were trialed, while others were implemented despite a lack of scientific consensus. This study aimed to identify how practice patterns to treat and manage COVID-19 changed over time in a cohort of patients in the University of Texas Medical Branch hospital system. Methods: Ninety participants with a COVID-19 diagnosis were included in the analysis for this study. Data was collected by a retrospective chart review, and included medications administered before and during current admission. Medications were categorized as: antiviral, antibiotic, steroid, supplement, antibody, hydroxychloroquine, and others. Results: Differences in therapeutic use were identified based on hospitalization status (outpatient or inpatient) and month admitted. The largest difference in the antiviral remdesivir (78%), requiring intravenous administration for up to ten days. In the outpatient setting, antibiotics, primarily azithromycin, were quite common. Additionally, month-to-month variation in steroid use and antibiotic use was observed. Conclusion: This study shows that adapting medical guidelines and strong media coverage played a role in the clinical management of COVID-19 patients. At times, some ineffective medications were prescribed such as hydroxychloroquine. Medical leaders and news coverage should collaborate closely in future public health emergencies to prevent the prescription of ultimately ineffective and potentially hazardous treatments.

Predictors of COVID-19 severity among a cohort of Egyptian patients

BackgroundAs the outbreak of COVID-19 progresses, prognostic markers for the identification of high-risk individuals are urgently needed. The angiotensin system is implicated in the pathogenesis of COVID-19 as ACE2 is the cellular receptor for SARS-COV-2 virus, and expression of the ACE2 gene could regulate an individual’s susceptibility to infection. In addition, the balance between ACE and ACE2 activity may play a role in the severity of COVID-19.Aim of workThe aim of the work is to explore the role of ACE1 I/D and ACE2 G8790A gene variants and serum ACE l/ACE2 ratio as risk factors for severity of COVID-19 infection.MethodsOne hundred and eighty COVID-19 patients were divided into three groups: mild (60 patients), moderate (60 patients), and severe (60 patients). The enzyme levels of ACE and ACE2 were measured by ELISA. ACE I/D (rs4646994) was assayed using PCR and ACE2 (rs2285666) gene variant was determined using real-time PCR.ResultsACE/ACE2 ratio was significantly lower in the mild group than in the moderate-to-severe group (P < 0.001). GG (reference) genotype and G allele of ACE2 were more frequent in mild group, AA (variant) genotype, and A allele were more frequent in severe group (P value < 0.001). In the multiple logistic regression, COVID-19 severity was associated with older age (> 50y) (OR 10.4, 95% CI 3.8–28.4, P < 0.001), comorbidities (OR 8.2, 95% CI 1.6–42.1, P 0.012), and higher ACE/ACE2 ratio (OR 8.3, 95% CI 3.7–18.6 P < 0.001) were independent significant predictors of severity. Haplotype analysis revealed that patients with D allele of the ACE gene combined with the A allele of the ACE2 gene had nearly double the risk of having severe COVID infection (OR = 1.9, 95% CI 1.1–3.5, P = 0.024).ConclusionOld age (> 50 years), presence of comorbidities, and a high ACE/ACE2 ratio are recognized as pivotal predictors of COVID-19 severity.

Altered spike IgG Fc N-linked glycans are associated with hyperinflammatory state in adult COVID-19 and Multisystem Inflammatory Syndrome in Children

Abstract Severe COVID-19 and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines. We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA. Spike IgG were more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with pro-inflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.

Thrombocytopenia and Other Hematological Features in COVID-19 Patients Referred to Shahid Mostafa Khomeini Hospital

Thrombocytopenia and Other Hematological Features in COVID-19 Patients Referred to Shahid Mostafa Khomeini Hospital

Filipino Rehabilitation Practitioners’ COVID-19 knowledge, practice and attitude: A cross-sectional study

Background: The rehabilitation team, consisting of physiatrists, physical and occupational therapists, and speech pathologists, faces heightened risk of COVID-19 exposure because of treatment practices in rehabilitation settings.Aim: The study aimed to assess the knowledge, practices and attitudes of rehabilitation professionals in treating COVID-19 patients and to determine potential associations with respondents’ demographic factors (e.g., age, gender, type of profession).Setting: The study was conducted in the Philippines.Methods: This cross-sectional study was conducted from June 2021 to July 2021. Researchers employed snowballing and purposive homogenous convenient sampling methods. Participants completed a 31-item online questionnaire via Google Forms.Results: A total of 410 rehabilitation professionals participated in the study. The total mean scores for knowledge, practices and attitudes are 41.14 ± 3.16, 104.54 ± 33.65 and 37.13 ± 3.55, respectively which were considered adequate. However, only 9.8% (n = 40) professional was actively treating COVID-19 patients with analysis of variance indicated that age, type of profession and gender did not significantly impact COVID-19 knowledge. However, age (p = 0.005) and type of profession (p = 0.004) were found to influence COVID-19 practices, with physiatrists exhibiting higher adherence. There was a strong positive correlation between age and positive COVID-19 attitudes (p 0.000).Conclusion: Filipino rehabilitation professionals have positive attitude, adequate knowledge and skills about COVID-19.Contribution: The study provides information to modify training courses and curricula to further improve the knowledge and practices related to COVID-19.

Innate immune response in COVID-19: single-cell multi-omics profile of NK lymphocytes in a clinical case series

BackgroundCOVID-19 pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) represents the biggest global health emergency in recent decades. The host immune response to SARS-CoV-2 seems to play a key role in disease pathogenesis and clinical manifestations, with Natural Killer (NK) lymphocytes being among the targets of virus-induced regulation.MethodsThis study performed a single-cell multi-omics analysis of transcripts and proteins of NK lymphocytes in COVID-19 patients, for the characterization of the innate immunological response to infection. NK cells were isolated from peripheral blood samples collected from adult subjects divided into 3 study groups: (1) non-infected subjects (Naïve group, n = 3), (2) post COVID-19 convalescent subjects (Healed group, n = 3) and (3) patients that were vaccinated against SARS-CoV-2 (Vaccine group, n = 3). Cells were then analysed by the BD Rhapsody System for the single-cell multi-omics investigation of transcriptome and membrane proteins.ResultsThe bioinformatic analysis identified 5 cell clusters which differentially expressed gene/protein markers, defining NK cell subsets as “Active NK cells” and “Mature NK cells”. Calculating the relative proportion of each cluster within patient groups, more than 40% of the Naïve group cell population was found to belong to Mature NKs, whereas more than 75% of the Vaccine group cell population belonged to the cluster of Active NKs. Regarding the Healed group, it seemed to show intermediate phenotype between Active and Mature NK cells. Differential expression of specific genes, proteins and signaling pathways was detected comparing the profile of the 3 experimental groups, revealing a more activated NK cell phenotype in vaccinated patients versus recovered individuals.ConclusionsThe present study detected differential expression of NK cell markers in relation to SARS-CoV-2 infection and vaccine administration, suggesting the possibility to identify key molecular targets for clinical-diagnostic use of the individual response to viral infection and/or re-infection.

Higher Serum Level of MMP-3 and Homocysteine in Patients Admitted With COVID-19

Background: SARS-CoV-2 predominantly affects the lungs, leading to severe acute respiratory syndrome (ARDS). The lack of specific biomarkers underscores the urgent need for novel indicators for early diagnosis and severity assessment of COVID-19. Specific Background: Matrix metalloproteinase-3 (MMP-3) is implicated in various inflammatory diseases, particularly viral infections, while homocysteine (Hcy) plays a crucial role in maintaining cell homeostasis and regulating inflammatory responses. Knowledge Gap: Despite their relevance in inflammation, the potential of MMP-3 and Hcy as biomarkers for COVID-19 remains underexplored. Aims: This study aimed to evaluate the serum levels of MMP-3 and Hcy in COVID-19 patients and assess their utility in diagnosis and severity prediction. Results: A study analyzing 90 serum samples from 60 ICU patients and 30 healthy controls found elevated CRP levels, higher Hcy and MMP-3 levels in the moderate group, but lower in the ICU group, with a significant correlation between MMP-3 activity and Hcy levels. Novelty: This research highlights the potential role of MMP-3 and Hcy as valuable biomarkers for COVID-19 diagnosis. Implications: While MMP-3 and homocysteine may aid in the diagnostic process, they could not be reliably used to predict severity outcomes in COVID-19 patients. Further studies are warranted to clarify the clinical implications of these biomarkers in the context of COVID-19. Highlights: MMP-3 and homocysteine identified as potential COVID-19 biomarkers. No correlation found between biomarkers and disease severity. Further research needed for clinical utility assessment. Keywords: COVID-19, MMP-3, homocysteine, biomarkers, diagnosis

Hypophysitis in COVID-19: a systematic review.

This systematic review aims to collect and examine recent research findings regarding hypophysitis in COVID-19 patients. We conducted a comprehensive literature review in English on the topic "Hypophysitis in COVID-19," using the MEDLINE (PubMed) database in July 2024. The selected articles were systematically tabulated and we have assessed in this review patient demographics, symptom presentation, imaging results, diagnosis, clinical management, and outcomes. Seven reported cases of post-COVID-19 hypophysitis were identified, comprising 4 (57%) females and 3 (43%)males, with a median age of 37 years. The interval between COVID-19 infection symptoms and the onset of hypophysitis ranged from 2 to 3 weeks. Initial symptoms included frontal headache in 4 (57%) cases and polyuria and polydipsia in 3 (43%)cases. Anterior or posterior hypopituitarism was observed in 6 (85%)patients. Radiological findings varied: 2 (28.5%) cases showed panhypophysitis, 3 (43%) cases exhibited gland enlargement with homogeneous contrast enhancement on magnetic resonance imaging (MRI), 1 case involved the loss of the posterior pituitary bright spot, and 1 case involved pituitary apoplexy/enlargement of the gland and infundibulum. No pituitary biopsies were performed. Four (57%) patients received glucocorticoid (GC) treatment. Long-term follow-up was documented in only one case, a 16-year-old female followed for 2 years reporting complete clinical and radiological resolution. Although rare, hypophysitis related to COVID-19 is documented in the literature exhibiting distinct characteristics such as a homogeneous gender prevalence, an average age of onset around 35 years, and primary symptoms of headache, polyuria, and polydipsia which are indicative of angiotensin-vasopressin deficiency. This is in contrast with primary autoimmune hypophysitis characterized by a female prevalence and typical symptoms with headache and visual impairment. Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement. Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.