Lichen planus after COVID-19 infection and vaccination

Background: Lichen planus (LP) is an inflammatory disorder believed to result from CD8+ cytotoxic T-cell (CTL) mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Method(s): Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 35 articles were selected based on subject relevance, and references within articles were also screened. Result(s): 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 150 cases of postvaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. Conclusion(s): LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Sleep Promotion in a Busy Inner City High Dependency Unit

Introduction: Critical care patients commonly have disrupted sleep patterns, with reduction of REM sleep, duration of sleep, increased fragmentation and loss of circadian rhythm.1 Causes include the patients' pathophysiology, medications administered and the busy critical care environment. Data collection showed that our patients were sleeping, on average, for a single block of sleep of 3.5 hours. Delirium rates and its known deleterious effects are highly associated with poor sleep, as well as an impairment of psychomotor performance and neurocognitive dysfunction. Sleep deprivation in the healthy population impairs lymphocyte action, cytokine production and pro-inflammatory balance, as well as a reduction in respiratory function and prolongation of respiratory support.2 Objectives: To firstly measure the sleep quality and explore the reasons behind poor sleep from the patients themselves and to gauge the MDT knowledge and interest in sleep, as a fundamental component of patient management. Then using the results we aimed to improve the duration and quality of the patients sleep on high dependency unit. Method(s): The Adapted Richard Campbell Sleep Questionnaire was given to all patients in the HDU over a 4 week period. Results were analysed, then stored for post intervention comparison. The duration of sleep was documented for all patients and a staff questionnaire was done to assess knowledge and concern of staff. Interventions included a staff sleep awareness week with education and prompts attached to the charting tables promoting sleep. Face masks and ear plugs were freely available to be distributed at the evening ward round. The critical care pharmacist identified medications that could alter the patients ability to achieve REM sleep - e.g. evening administered PPIs, and melatonin was commenced early when sleep was troublesome. Estates fixed soft close doors and soft closed bins supplied for clinical areas. After interventions, there was a further 4 week study period where the above factors were repeated. The need for natural light was highlighted and thus this was optimized in the ward environment and those physiologically able were offered trips outdoors to facilitate normal day night wake cycle. With the COVID pandemic ongoing we also endeavored to limit movement overnight of venerable patients. Result(s): The original data collection was of 45 patients with multiple data points, and the second of 27 patients with multiple data points. Results from the Adapted Richard Campbell Sleep Questionnaire were compared using a one tailed students t test. There were significant increases in the subjective quality of sleep (p=0.046) and quantity of sleep (p=0.00018). Reasons given as to improvement of sleep were reduction in discomfort from monitoring and the bed (p=0.026), reduced ambient light (p=0.031) and reduced impact from the presence of other patients (p=0.002). Conclusion(s): There was marked improvement in the awareness of the importance of sleep within the critical care team after education promoting a change in attitude and culture towards sleep. We are planning a second iteration targeting sedation, noise from monitors and staff and overnight interventions. Although this has been done with level 2 patients, extension to level 3 areas would be beneficial.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

Inherited deficiency of the OAS-RNase L pathway in children with MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.Copyright © 2023 Elsevier Inc.

Cellular and Molecular Atlas of Peripheral Blood Mononuclear Cells from a Pregnant Woman after Recovery from COVID-19

Objective This study aimed to investigate the immune response of a pregnant woman who recovered from the coronavirus disease 2019 (COVID_RS) by using single-cell transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) and to analyze the properties of different immune cell subsets. Methods PBMCs were collected from the COVID_RS patient at 28 weeks of gestation, before a cesarean section. The PBMCs were then analyzed using single-cell RNA sequencing. The transcriptional profiles of myeloid, T, and natural killer (NK) cell subsets were systematically analyzed and compared with those of healthy pregnant controls from a published single-cell RNA sequencing data set. Results We identified major cell types such as T cells, B cells, NK cells, and myeloid cells in the PBMCs of our COVID_RS patient. The increase of myeloid and B cells and decrease of T cells and NK cells in the PBMCs in this patient were quite distinct compared with that in the control subjects. After reclustering and Augur analysis, we found that CD16 monocytes and mucosal-Associated invariant T (MAIT) cells were mostly affected within different myeloid, T, and NK cell subtypes in our COVID_RS patient. The proportion of CD16 monocytes in the total myeloid population was increased, and the frequency of MAIT cells in the total T and NK cells was significantly decreased in the COVID-RS patient. We also observed significant enrichment of gene sets related to antigen processing and presentation, T-cell activation, T-cell differentiation, and tumor necrosis factor superfamily cytokine production in CD16 monocytes, and enrichment of gene sets related to antigen processing and presentation, response to type II interferon, and response to virus in MAIT cells. Conclusion Our study provides a single-cell resolution atlas of the immune gene expression patterns in PBMCs from a COVID_RS patient. Our findings suggest that CD16-positive monocytes and MAIT cells likely play crucial roles in the maternal immune response against severe acute respiratory syndrome coronavirus 2 infection. These results contribute to a better understanding of the maternal immune response to severe acute respiratory syndrome coronavirus 2 infection and may have implications for the development of effective treatments and preventive strategies for the coronavirus disease 2019 in pregnant women.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

The effect of circulating cytokines on cardiovascular patients infected with the Coronavirus

The coronavirus illness (COVID-19) is caused by serious acute respiratory disorder coronavirus 2 (SARS-CoV-2), moreover known as the COVID-19 virus. After the first-ever reports of COVID-19 in December 2019, the malady spread quickly. In January 2020, the WHO announced the outbreak a Public Health Emergency of Worldwide Concern, and by March 2020, the WHO characterized the episode as a global widespread . The current study aimed to detect the effect of SARS-CoV-2 infection in heart patients and study their immune response by detecting the levels of some cytokines, which may end in a cytokine storm and may lead to death. In this study, one hundred-eight subjects were enrolled on two comparison case-control groups, the case group included 54 patients suffering from SARS-COV2, all were selected from those who were admitted to the Intensive Care Unit (ICU), and were diagnosed by a specialist physician with severe acute respiratory syndrome due to SARS-COV2 documented by Real-Time Polymerase Chain Reaction( RT-PCR ) besides other clinical and laboratory criteria in Marjan Medical City in Babylon province, AL-Amal Hospital for Communicable Diseases and AL-Hakeem Hospital, Najaf/Iraq, for a period from March 2022 to October 2022 to evaluate the role of some selected serological among patients with SARA-COV2 . The control group in this study included 54 subjects, divided into three groups (Apparent Healthy, patients suffered from SARS-COV2, patients suffered from CVD). Blood samples were examined through immunological methods, and an enzyme-linked immunosorbent assay (ELISA) was adopted for the detection of the concentration of TNF-alpha, IL6, IL-10,1L-12 and CCL2 .The immunological evaluation to clarify the theory of cytokines storm carried in the present study revealed that (TNF-alpha, IL6, IL-10,1L-12, and CCL2) for patients with COVID-19 and CVD was significantly higher than all the comparison group. The study reported that interleukin (6, 10, 12) and TNF-a are significantly increased in patients with covid19, CVD, and COVID-19 patients only, compared to healthy people. furthermore, IL-6 and IL-12 levels increased in patients with CVD only when compared to healthy people. There is a significant increase in CCL2 in all study groups compared to healthy people who have lower levels and this study indicated that the infection with Covid disease was severe and critical in most patients with CVD. This increased the number of deaths among them.Copyright © 2021 Muslim OT et al.

Oral Microbiome and Innate Immunity in Health and Disease: Building a Predictive, Preventive and Personalized Therapeutic Approach

An average person carries 1 to 2 kg of microbes in the alimentary track, including the oral cavity. There are more bacteria in a person's mouth than the total human population in the entire world. Oral health is critical to the general systemic health of an individual. The harmonious co-existence between more than 1000 bacterial species and the host's immune system underpins sustained, long-term homeostasis, the sine qua non of oral health. In a similar manner, global oral health is essential for general population health of the world. Since our last review of this subject in 2019, while significant clinical advances continue, the disparity, lack of prevention, insufficient care, and political unrest have persisted or significantly deteriorated. This review focuses on the following important questions: 1.What is oral microbiome? How to detect, characterize, compare, report, and interpret the results?2.How does oral microbiome affect and respond to local and systemic innate immunity?3.What is the role of oral microbiome in the pathogenesis of diseases of the mouth?4.What are the impacts of oral health or the lack of it at the systemic level?5.Why is oral health important at the population level?6.How can the healthcare providers restore and sustain harmonious co-existence between host and oral microbiome?Copyright © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

IMMUNOGENICITY OF SARS-CoV-2 mRNA VACCINATION IN IDIOPATHIC CD4 LYMPHOPENIA

Background: The rapid development of SARS-CoV-2 mRNA vaccines has been a remarkable success of the COVID-19 pandemic, but vaccine-induced immunity is heterogeneous in immunocompromised populations. We sought to determine the immunogenicity of SARS-CoV-2 mRNA vaccines in a cohort of people with idiopathic CD4 lymphopenia (ICL). Method(s): 25-patients with ICL followed at the National Institutes of Health on a natural history protocol were evaluated between 2020-2022. Blood and serum was collected within 4-12 weeks after their second and/or third SARS-CoV-2 mRNA vaccine dose. Twenty-three matched healthy volunteers (HVs) provided blood samples at similar timepoints post-mRNA vaccination on a separate clinical protocol. Pre-vaccine blood samples were also used when available. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell stimulation assays were performed to quantify SARS-CoV-2 specific T-cell responses. Comparisons were made with Wilcoxon test. Result(s): Twenty-participants with ICL had samples collected after their second mRNA vaccine and 7-individuals after the third dose. Median age at vaccination was 51-years (IQR: 44-62) and 12 were women (48%). Median CD4 T-cell count was 150 cells/muL (IQR: 85-188) at the time of vaccination, and 11-individuals (44%) had a baseline CD4 count <=100 cells/muL. HVs had a median age of 54-years (IQR: 43-60) with 13-women (56.5%). Anti-spike IgG antibody levels were significantly greater in HVs than those with ICL after 2-doses. Lower SARS-CoV-2 IgG antibody production was primarily observed in those with baseline CD4 T-cells <=100 cells/mul (Figure-1A). The decreased production in ICL remained after a third vaccine dose (Figure-1B). There was a significant correlation between anti-spike IgG and baseline CD4 count. Spike-specific CD4 T-cell responses in volunteers compared to those with ICL demonstrated similar levels of activation induced markers (CD154+CD69+) and cytokine production (IFNgamma+, TNFalpha+, IL2+) after two or three mRNA vaccine doses. Quantitatively the smallest responses were observed in those with lower baseline CD4 T-cells (Figure 1C-D). Minimal SARS-CoV-2 CD8 T-cell responses were detected in both groups. Conclusion(s): Patients with ICL and baseline CD4 T-cells >100 mount similar humoral and cellular immune responses to SARS-CoV-2 vaccination as healthy volunteers. Those with baseline CD4 T-cells <=100 have impaired vaccine- induced immunity and should be prioritized to additional boosters and continue other risk mitigation strategies. (Figure Presented).

Covid-19 Vaccination Impacts Functional Immune Responses and Plasma Proteome in Plwh

Background: The impact of COVID-19 infection or COVID-19 vaccination on the immune system of people living with HIV (PLWH) is unclear. We therefore studied the effects of COVID-19 infection or vaccination on functional immune responses and systemic inflammation in PLWH. Method(s): Between 2019 and 2021, 1985 virally suppressed, asymptomatic PLWH were included in the Netherlands in the 2000HIV study (NCT039948350): 1514 participants enrolled after the start of the COVID-19 pandemic were separated into a discovery and validation cohort. PBMCs were incubated with different stimuli for 24 hours: cytokine levels were measured in supernatants. ~3000 targeted plasma proteins were measured with Olink Explore panel. Past COVID-19 infection was proven when a positive PCR was reported or when serology on samples from inclusion proved positive. Compared were unvaccinated PLWH with and without past COVID-19 infection, and PLWH with or without anti-COVID-19 vaccination excluding those with past COVID-19 infection. Result(s): 471 out of 1514 participants were vaccinated (median days since vaccination: 33, IQR 16-66) and 242 had a past COVID-19 infection (median days since +PCR: 137, IQR 56-206). Alcohol, smoking, drug use, BMI, age, latest CD4 count and proportion with viral blips were comparable between groups. Systemic inflammation as assessed by targeted proteomics showed 89 upregulated and 43 downregulated proteins in the vaccinated participants. In contrast, individuals with a past COVID-19 infection display lower levels of 138 plasma proteins compared to the uninfected group (see figure). 'Innate immune system' and 'cell death' were upregulated in pathway analysis in vaccinated PLWH, but downregulated in COVID-19 infected participants. The increased systemic inflammation of the COVID-19 vaccinated group was accompanied by lower TNF-alpha and IL-1beta production capacity upon restimulation with a range of microbial stimuli, while production of IL-1Ra was increased. In COVID-19 infected PLWH only a reduced production of TNF-alpha to S. pneumonia was significant. Vaccinated PLWH also showed upregulation of platelet aggregation pathways. Conclusion(s): COVID-19 vaccination in PLWH leads to an increased systemic inflammation, but less effective cytokine production capacity of its immune cells upon microbial stimulation. This pattern is different from that of COVID-19 infection that leads to a decreased inflammatory profile and only minimal effects on cytokine production capacity. (Figure Presented).

CO-SPROUT: A PILOT DOUBLE-BLINDED RANDOMISED CONTROL TRIAL of BROCCOLI SPROUT for PREGNANT WOMEN with COVID-19: STUDY PROTOCOL

Background: COVID-19 is caused by SARS-CoV-2 and has is responsible for over 619 million infections and over 6.5 million deaths globally since identification in 2019. Infection during pregnancy is associated with increased adversity including increased risks of admission to intensive care, increased ventilatory support, preeclampsia, preterm birth and maternal death. Vaccination remains the best protection against severe disease. The majority of trials for novel or repurposed COVID-19 therapies including mRNA vaccinations have excluded pregnant or lactating women despite being an at-risk population. Broccoli sprout extract contains a naturally occurring phytonutrient sulforaphane which upregulates the Nrf2 transcription factor resulting in expression of antioxidant proteins, anti-inflammatory effects and has demonstrated anti-viral effects in-vitro . Severe COVID-19 results in excessive cytokine production resulting in a proinflammatory state with significant oxidative stress and multi-organ dysfunction with evidence of placental abnormalities in almost half of infected mothers. Method(s): CO-Sprout is a pilot, double blinded, placebo controlled randomised trial that is recruiting pregnant women ( n = 60) between 20 and 36 weeks completed gestation with COVID-19 diagnosed within 5 days. Participants are randomised to either broccoli sprout capsules (containing 21 mg sulforaphane) or identical placebo (microcrystalline cellulose) twice daily for 14 days. The primary outcome will be duration (days) of COVID-19 related symptoms and other exploratory outcomes including unplanned hospital admissions, birth outcomes, inflammatory markers, microbiome and placental changes. Patients are recruited through maternity departments at Monash Health and Jessie McPherson Private Hospital. Result(s): Trial in progress. Conclusion(s): Trial results to be published after trial completion.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Herbal plant extracts or purified phytocomponents have been extensively used to treat several diseases since ancient times. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs. In Ayurveda, the polyherbal formulation is known to exhibit better therapeutic efficacy compared to a single herb. This review focuses on six key ayurvedic herbal plants namely, Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra/Licorice, Zingiber officinale, Emblica officinalis and Ocimum sanctum. These plants possess specific phytocomponents that aid them in fighting infections and keeping body healthy and stress-free. Plants were selected due to their reported antimicrobial and anti-inflammatory effects in several diseases and effectiveness in controlling viral pathogenesis. An ad-vanced literature search was carried out using Pubmed and google scholar. Result(s): These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, anti-microbial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related dis-eases. The importance of these medicinal herbs becomes highly prominent as it maintains the har-monious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy in fighting infectious diseases like Covid-19. It opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulations.Copyright © 2023 Bentham Science Publishers.

New insights into the effects of hydroxychloroquine in COVID-19

In late 2019 until 2021, the novel coronavirus disease (COVID-19) has become pandemic. This disease is related to severe inflammatory symptoms of the respiratory epithelial cells and the dysfunction of several organs. One of the suggested drugs to reduce the inflammation caused by COVID-19 is hydroxychloroquine. Studies have shown this drug blocks the inflammatory pathway of nuclear factor-kappaB by blocking P21 activated kinase 1. Also, nanoparticle vaccines Poly Lactide-Glycolide) Acid (PLGA) containing hydroxychloroquine are effective in cancer by stimulating CD8T + cells responses. This study assumed that hydroxychloroquine was effective in inhibiting COVID-19 with these mechanisms.Copyright © 2021 Health Biotechnology And Biopharma. All Rights Reserved.

Inflammatory Markers Associated with Adverse Outcome among Covid-19 Patients: An Observational Study

Background: Ever since the beginning of the Covid-19 pandemic, pathologists started investigating the laboratory markers that can assist in predicting the outcome among Covid-19 patients presenting to the emergency/inpatients department of hospital. Aim(s): This study aimed to investigate the association between the blood/serum levels of various inflammatory biomarkers at the time of admission to hospital and mortality among COVID-19 patients. Material(s) and Method(s): This was a single centre, hospital (inpatient) based prospective cohort study involving 508 Covid-19 patients admitted to the study institute. We collected data on CRP, D-dimer, LDH, Ferritin, and IL-13 levels at the time of admission. We also assessed the correlation between CT Severity score and the inflammatory markers. Result(s): Among 508 included patients: 53 (10.4%) patients died, 73 (14.4%) patients required admission to Intensive Care Unit studied, 39 (7.7%) patients required mechanical ventilation, 23 (4.5%) had Coma and 328 (64.6%) patients were discharged from hospital without any complications. The levels of all measured inflammatory markers were significantly higher (worse) (p <0.05) among patients suffered adverse complications (including death) during treatment. In addition, the level of several inflammatory markers strongly and positively correlated with CT scan findings. Conclusion(s): The level of all inflammatory markers was significantly higher among Covid-19 patients who died during the treatment. However, more research is needed to identify the upper cut-off levels of inflammatory markers to identify patients who are at increased risk of complications including death.Copyright © 2023, Dr. Yashwant Research Labs Pvt. Ltd.. All rights reserved.

Memory T cell responses in seronegative older adults following SARS-CoV-2 vaccination

Generating memory T cell responses besides humoral immune responses is essential when it comes to the efficacy of a vaccine. In this study, the presence of memory T cell responses after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac) in seronegative and seropositive elderly individuals were examined. CD4+ and CD8+ memory T cell proliferation and IFN-gamma production capacities were evaluated. Additionally, clinical frailty scale (CFS) and FRAIL scales of the individuals were scored. CD4+ memory T cell responses more prominent than CD8+ memory T cells. In seronegative individuals, 80% of them had memory CD4+ and IFN-gamma, whereas 50% of them had memory CD4+ and all of them had IFN-gamma responses. Additionally, 40% of seronegative patients and 50% of seropositive patients had memory CD8+ responses. To sum up, humoral immune responses are not associated with memory T cell responses, and in seronegative individuals, memory T cell responses can be detected.Copyright © 2022

Clinical and immunological impact of booster immunization with recombinant mRNA vaccines for SARS-CoV-2 in patients with pemphigus and bullous pemphigoid

Vaccines based on recombinant mRNA technology helped to control the pandemic caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). Clinical trials for showed that these vaccines are safe and effective and promote a strong type 1 driven T cell response. Yet, several reports claimed that SARS-CoV-2 mRNA vaccination might favor the onset, worsening or the reactivation of autoimmune disorders like pemphigus and bullous pemphigoid. However, no study demonstrated a direct immunological link between mRNA vaccination and disease appearance/worsening. We aimed to analyze the immunological and clinical effects exerted by mRNA booster vaccinations for SARS-CoV-2 in a cohort of patients with pemphigus (n=9), bullous pemphigoid (n=4) and in healthy individuals (n=5). Patients and healthy individuals were monitored at baseline, and after two and four weeks of mRNA vaccination. We assessed the clinical disease status, antibodies against the SARS-CoV-2 spike protein, antibody levels for BP180/230, DSG1/3 and tetanustoxoid. We also determined the distribution of peripheral T helper / T follicular cell subsets, intracellular cytokine production of T cells and cytokine serum levels. Our results show that booster vaccination increased anti spike protein IgG, while tetanustoxoid igC and skin-specific autoantibody titers were not or minimally affected. We observed an increase in Th1/Th17.1 cells, together with an increase in the intracellular production of IFN-gamma, IL-4 and IL-21 in peripheral T cells of pemphigus patients. Importantly, clinical activity in both remittent patients and in patients with active disease remained stable. In summary, vaccination with mRNA vaccines induced a specific activation of the humoral system with production of protective antibodies against the Sars-CoV-2 spike protein without affecting autoimmune disease activity in patients with pemphigus and bullous pemphigoid.Copyright © 2023

Effect of recombinant interferon alfa-2b on cytokine production activity of immune system cells in children with COVID-19.

The clinical efficacy of recombinant IFN-alpha2b in therapy for COVID-19 in children is the basis for studying the parameters of the cytokine production activity of immune system cells and will allow to optimize antiviral therapy regimens. Objective. To study the effect of recombinant IFN-alpha2b on serum IFN-alpha and IFN-gamma concentrations and their synthesis by immune system cells in children with COVID-19. Materials and methods. Peripheral blood samples from 100 patients aged 1 to 17 years (1-7 years - 50 people, 8-17 years - 50 people) with a moderate course of COVID-19 were examined. Patients in the study group received recombinant IFN-alpha2b as part of complex therapy. Patients in the comparison group received antiviral therapy with Arbidol. Multiplex analysis was used to determine serum IFN-alpha and IFN-gamma concentrations and the level of their synthesis by immune system cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine serum concentrations of antibodies to IFN-alpha. Results. Combination therapy with recombinant IFN-alpha2b in children of both age groups led to an increase in serum IFN-alpha concentrations compared to baseline values prior to treatment, in children in the control group and patients with COVID-19 after treatment with Arbidol. There were no significant changes in serum IFN-alpha and IFN-gamma concentrations and their synthesis in intact and PHA-stimulated cells in children of both age groups during treatment with Arbidol. Serum concentrations of antibodies to IFN-alpha during treatment with recombinant IFN-alpha2b did not depend on the age of children and remained within the reference range. Conclusion. A significant increase in serum IFN-alpha concentrations and restoration of its synthesis level induced by PHA to reference values indicate that the use of recombinant interferon medications with their antiviral and immunomodulatory effects should become an integral part of COVID-19 therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

COVID-19 and Pain

SARS-CoV-2 causes COVID-19, which includes acute respiratory tract infections with a variety of manifestations such as pneumonia and bronchiolitis which are accompanied by other symptoms such as wheezing, cough, respiratory distress, and pain. The novel Coronavirus has caused millions of deaths and increasing challenges for healthcare professionals globally. When the virus enters our organism through nasal mucosa it is identified by the innate immune system such as macrophages and mast cells, therefore producing pro-inflammatory cytokines including IL-1beta, IL-6, and TNF. The production of cytokines mediates fever, malaise, depression, anxiety, loss of appetite, hyperalgesia, and pain. Here in this paper, we report the interrelationship between COVID-19 and pain.Copyright © by BIOLIFE.

Ayurvedic Herbs Advised for COVID-19 Management: Therapeutic Potential and Clinical Relevance

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. There is no effective medication for COVID-19 as of now, so it would be good to take preventive measures that not only boost our immunity but also fight against infections. The use of traditional Chinese medicine in China to treat COVID-19 patients sets the prototype demonstrating that traditional medicines can contribute to prevention and treatment successfully. In India, the Ministry of AYUSH (Ayurveda, Yoga, Unani, Siddha, Homeop-athy) released a self-care advisory during the COVID-19 crisis as a preventive aspect. This review article discusses the therapeutic potential and clinical relevance of some herbs [(Tulsi (Ocimum sanctum), Haridra (Curcuma longa), Tvaka (Cinnamon), Maricha (Piper longum), Shunthi (Zingi-ber officinale), Munakka (Dried grapes), Lavang (Syzigiumaromaticum), Pudina (Mentha arvensis), and Ajwain (Trachyspermum ammi)] advised by AUYSH to take during COVID-19 infection. They are effective in COVID-19 management, therefore, authors have discussed their detailed traditional uses as therapeutics and spotted scientific insight and clinical significance of the herbs mentioned above along with their mechanistic viewpoint, adequately, on a single platform. Provided information could be a treasure to open up a new research arena on natural products to manage human health crises effectively, caused not only by COVID-19 but also by other infectious diseases.Copyright © 2023 Bentham Science Publishers.

The interaction between 2019-nCoV and interferon.

COVID-19 has swept across the world, causing widespread epidemics and millions of life lost worldwide. After infected with 2019-nCoV, the body quickly mobilizes the innate immune response and produces type interferon (IFN-). IFN- plays an important role in virus clearance in the early stage of disease. This article reviews the innate immune recognition after virus infection and the interaction between 2019-nCoV and IFN-, which would be conductive to understanding the pathogenesis and antiviral treatment of COVID-19.Copyright © 2021 Chinese Medical Association