Cytokine Profile in Different Post-Covid-19 Condition Phenotypes

Background: At least 10% of SARS-CoV-2 infected patients suffer from persistent symptoms for >12 weeks, known as post-COVID-19 condition (PCC) or Long Covid. Reported symptomatology is diverse with >200 physical and neurological debilitating symptoms. Here, we analyzed pro-inflammatory cytokine levels as a potential mechanism underlying persistent symptomatology. Method(s): Clinical data and samples used belong to the KING cohort extension, which includes clinically well characterized PCC (N=358, 59 persistent symptoms evaluated), COVID-19 recovered and uninfected subjects. We used Gower distances to calculate symptom's similarity between PCC and Ward's hierarchical clustering method to identify different symptom patterns among PCC patients. Cytokine levels of randomly selected PCC, recovered and uninfected subjects (N=193) were measured on plasma samples collected >6 months after acute infection using the 30-Plex Panel for Luminex. Mann- Whitney t-test was used to compare PCC vs recovered groups and Kruskal-Wallis t-test for >2 groups comparisons (PCC vs recovered vs Uninfected and within PCC clusters). FDR correction was applied for statistical significance (p-adj). Result(s): Hierarchical clustering identified 5 different PCC clusters according to their symptomatology, where PCC3 and PCC5 clusters showed higher prevalence of women ( >80%) and more persistent symptoms, while acute COVID-19 was mild in >80% of the patients. We selected 91 PCC (belonging to each cluster), 57 recovered and 45 uninfected subjects for cytokine profiling (Table 1). 13 soluble markers were significantly elevated (IL-1beta, Eotaxin, MIP-1beta, MCP-1, IL-15, IL-5, HGF, IFN-alpha, IL-1RA, IL-7, MIG, IL-4 and IL-8) in PCC and recovered groups compared to uninfected subjects (all p-adj< 0.04). In addition, PCC subjects tended towards higher levels of IL-1RA compared to recovered group (padj= 0.071). Within PCC clusters, FGF-basic and RANTES were elevated while IL-2 and MIG were decreased in PCC3 and PCC5 compared to the other PCC clusters (all p-adj< 0.04). TNF-alpha, IP-10, G-CSF and MIP-1alpha were decreased in PCC3 and PCC5 not reaching statistical significance (all p-adj=0.07). Conclusion(s): Some cytokines remained altered in all SARS-CoV-2 infected subjects independently of persistent symptoms after 6 months from acute infection. Differences between PCC and recovered individuals are limited after correction. Importantly, PCC cytokine profiles showed differences between clusters, which suggests different PCC subsyndromes with distinct etiology. Subjects Characteristics (Table Presented).

Mechanisms of Atrial Fibrillation in Covid-19

Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.

Cells and cytokines analysis in bronchoalveolar lavage (BAL) fluid during or after non-severe COVID-19 pneumonia

Introduction: Findings on cells and cytokines analyses in BAL are poorly described during and after resolution of non-severe COVID-19 pneumonia, that are the objectives of this study Methods: This study included 54 pts in whom a BAL was performed (04/2020-02/2021) for the diagnosis or follow-up of suspected COVID-19 pneumonia. Cytological and cytokine analyses (IL-1b, IL-6, IL-8, IL-10, TNFa, IFNg, HGF, TGFb) were performed in BAL blinded to the classification of pts into 3 groups: non-COVID (n=20);COVID (n=13) and post-COVID pneumonia (n=24) Results: Total cell counts were not different between groups. % macrophages were similar between non-COVID and COVID groups, while % neutrophils (PN) were higher - although NS in non-COVID and % lymphocytes (Ly) higher in COVID pneumonia (p<0.024). Plasmocytes were observed in 4/13 COVID and in 1/20 of non-COVID BAL (p=0.042). Compared with COVID pneumonia, post-COVID BAL showed lower % PN, but a persistent Ly alveolitis. Alveolar Ly, in COVID/post-COVID groups were mainly of a CD3/CD4-T cell subset. TGFb was not measurable in the 3 groups. IL-10, IFNg and HGF BAL levels were higher in COVID vs non-COVID pneumonia group (p=0.0128, p=0.005, p=0.007). IL-6, IL-8, IL-10, TNFa, IFNg and HGF levels were lower in post-COVID compared to COVID BAL (all p< 0.005). In COVID pts, IL-1b and IL-6 inversely correlated with %Ly in BAL (r=-0.8, p=0.005;r=-0.7, p=0.02, respectively Conclusion(s): Lymphocytic alveolitis associated with plasmacytosis is found in non-severe COVID-19 pneumonia. This alveolitis is associated with the presence of IL-6, IL-8, IL-10, TNFa, IFN g and HGF. BAL alveolitis and cytokine levels normalize in post-COVID-19 pneumonia.

Rapid increase of myeloid-derived suppressor cells and prolonged innate immune dysfunctions in patients with COVID-19

Background: PMN and monocytic myeloid-derived suppressor cells (PMN-MDSCs, M-MDSCs) are immunosuppressive cells rising during infections. Aim: To characterize the dynamic of MDSCs in relation with immune parameters in COVID-19 patients followed for 3 months. Methods: 56 SARS-CoV-2 infected adult patients hospitalized at CHUV were included. Blood was obtained at inclusion and 3 months later in 21 patients, and from 10 healthy controls. Blood was stimulated with TLR ligands. Leukocyte populations and cytokines were analyzed by flow cytometry, mass cytometry, multiplex bead assay and ELISA. Results: At hospital admission, PMN-MDSCs and M-MDSCs were increased 2-4-fold in COVID-19 patients (P <0.05). PMN-MDSCs and M-MDSCs counts were higher in severe than in moderate COVID-19 patients (P <0.005). PMN-MDSCs and M-MDSCs correlated positively with EGF and HGF (P <0.05). M-MDSCs correlated positively with IL-1β, IL-7, PDGF and VEGF (P <0.05). In whole blood stimulated with TLR ligands, the proportion of TNF and IL-6- producing monocytes and DCs were reduced in patients. After 32 months, MDSCs were back to normal levels, while the production of cytokines by blood, monocytes and DCs was still largely affected. Conclusions: PMN-MDSCs and M-MDSCs were elevated and correlated with disease severity in patients analyzed at hospitalization. Innate immune blood responses were impaired in patients, which persisted for up to 3 months. Our results suggest that COVID-19 induces rapid and long-standing innate immune dysregulation.

An evaluation of nutritional status and specific nutritional issues during a rehabilitation period post COVID-19 infection

Patients recovering from COVID-19 infection are at a high risk of malnutrition, reduced nutritional intake and decline in muscle mass and strength.1 The aim of this service evaluation is to describe baseline characteristics, quantify risk of malnutrition, provide an overview of nutritional status and nutritional related outcomes for patients recovering post COVID-19 infection on rehabilitation wards. Data collection occurred between the 1st of February and the 1st of July 2021. This cohort included all patients who were recovering from COVID-19, who were referred to dietetic service and transferred to a rehabilitation ward. Demographic data and nutritional parameters were gathered from electronic records, and dietetic assessments. A total of 54 patients were included: 59% male, 41% female. Ages ranged from 46 to 95 years with average age of 79.9 years and average length of hospital stay of 92 days. One fifth of those included had an ICU stay. Where data was available on sarcopenia risk, 50% were identified as at risk of sarcopenia. Of those where serum 25-hydroxyvitamin D was checked, 45% had insufficient vitamin D levels. A nutrition focused physical exam was completed for 18 patients (one third of the cohort). Using this exam, 61% were diagnosed with moderate or severe malnutrition. At least 15% of patients experienced significant weight loss between their admission to the hospital compared to their weight on admission to post COVID-19 rehabilitation ward. Of those where Malnutrition Screening Tool was completed on admission to COVID-19 rehabilitation ward, 33% were identified as at risk of malnutrition. On discharge from the dietetic caseload, the proportion of those identified at risk of malnutrition using this tool decreased to 18%. During the period from admission to COVID-19 rehabilitation ward and discharge from dietetic service, 42% gained weight, 54% maintained their weight, 4% lost weight. Of those with data available regarding nutritional intake on admission to COVID-19 rehabilitation ward, 28% met energy requirements and 44% met protein requirements. On discharge from dietetic service these proportions increased to 66% meeting energy requirements and 74% meeting protein requirements. The average kcal intake on admission to COVID-19 rehabilitation increased from 1531kcal to 1778kcal on discharge and the average protein intake increased from 67g on admission to post COVID-19 rehabilitation to 75g on discharge. These results demonstrate the high prevalence of malnutrition and high risk of sarcopenia in patients admitted for rehabilitation post COVID-19 infection. With dietetic input, improvements were observed in patient’s nutritional intake, and nutritional outcomes such as weight and malnutrition risk. These results illustrate the need for early dietetic input in those recovering post COVID-19 infection to optimise nutritional status and nutritional outcomes. References: 1. Anker M. S., Landmesser U., von Haehling S et al. Weight loss, malnutrition, and cachexia in COVID-19: facts and numbers. Journal of Cachexia, Sarcopenia and Muscle, 12, 9– 13.

Management of COVID-19-A Review

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also;in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts;also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

MRNA COVID vaccines dramatically increase endothelial inflammatory markers and ACS risk as measured by the PULS cardiac test: A warning

Our group has been using the PLUS Cardiac Test (GD Biosciences, Inc, Irvine, CA) a clinically validated measurement of multiple protein biomarkers which generates a score predicting the 5 yr risk (percentage chance) of a new Acute Coronary Syndrome (ACS). The score is based on changes from the norm of multiple protein biomarkers including IL-16, a proinflammatory cytokine, soluble Fas, an inducer of apoptosis, and Hepatocyte Growth Factor (HGF)which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue, among other markers. Elevation above the norm increases the PULS score, while decreases below the norm lowers the PULS score. The score has been measured every 3-6 months in our patient population for 8 years. Recently, with the advent of the mRNA COVID 19 vaccines (vac) by Moderna and Pfizer, dramatic changes in the PULS score became apparent in most patients. This report summarizes those results. A total of 566 pts, aged 28 to 97, M:F ratio 1:1 seen in a preventive cardiology practice had a new PULS test drawn from 2 to 10 weeks following the 2 COVID shot and was compared to the previous PULS score drawn 3 to 5 months previously pre- shot. Baseline IL-16 increased from 35=/-20 above the norm to 82 =/- 75 above the norm post-vac;sFas increased from 22+/- 15 above the norm to 46=/-24 above the norm post-vac;HGF increased from 42+/-12 above the norm to 86+/-31 above the norm post-vac. These changes resulted in an increase of the PULS score from 11% 5 yr ACS risk to 25% 5 yr ACS risk. At the time of this report, these changes persist for at least 2.5 months post second dose of vac.We conclude that the mRNA vacs dramatically increase inflammation on the endothelium and T cell infiltration of cardiac muscle and may account for the observations of increased thrombosis, cardiomyopathy, and other vascular events following vaccination.