Coronavirus Disease 2019 Therapy Research Articles

Human cellular restriction factors that target SARS-CoV-2 replication

Millions of people have died and a worldwide economic catastrophe has been brought on by the coronavirus disease 2019 (COVID-19) pandemic. Infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may presently be treated with less than 10 antiviral drugs such as Remdesivir. The need for medical intervention due to sickness has led to unprecedented research efforts to study the biology of coronaviruses. Additionally, there is a strong likelihood that coronaviruses will cause pandemics in the future. All viruses cannot replicate optimally due to host restriction factors. Given that they are genetically more stable than viral targets and may be shared by similar viruses, these antiviral host factors provide appealing targets for antiviral treatment. The identification of antiviral host factors that are a component of human innate immunity and that prevent the completion of the SARS-CoV-2 life cycle has been made possible by the deployment of several “omics” technologies. In this review, we provide an overview of the antiviral host factors that limit the replication of SARS-CoV-2 in this, which were mostly discovered using functional genetic and interactome screening. Important cellular mechanisms for the SARS-CoV-2 life cycle are covered. Finally, we highlight host restriction factors that could be targeted by clinically approved molecules and the induction of these factors as potential antiviral therapies for COVID-19.

SARS-CoV-2-Specific T-Cell as a Potent Therapeutic Strategy against Immune Evasion of Emerging COVID-19 Variants.

Despite advances in vaccination and therapies for coronavirus disease, challenges remain due to reduced antibody longevity and the emergence of virulent variants like Omicron (BA.1) and its subvariants (BA.1.1, BA.2, BA.3, and BA.5). This study explored the potential of adoptive immunotherapy and harnessing the protective abilities using virus-specific T cells (VSTs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VSTs were generated by stimulating donor-derived peripheral blood mononuclear cells with spike, nucleocapsid, and membrane protein peptide mixtures. Phenotypic characterization, including T-cell receptor (TCR) vβ and pentamer analyses, was performed on the ex vivo-expanded cells. We infected human leukocyte antigen (HLA)-partially matched human Calu-3 cells with various authentic SARS-CoV-2 strains in a Biosafety Level 3 facility and co-cultured them with VSTs. VSTs exhibited a diverse TCR vβ repertoire, confirming their ability to target a broad range of SARS-CoV-2 antigens from both the ancestral and mutant strains, including Omicron BA.1 and BA.5. These ex vivo-expanded cells exhibited robust cytotoxicity and low alloreactivity against HLA-partially matched SARS-CoV-2-infected cells. Their cytotoxic effects were consistent across variants, targeting conserved spike and nucleocapsid epitopes. Our findings suggest that third-party partial HLA-matching VSTs could counter immune-escape mechanisms posed by emerging variants of concern.

Impact of Corticosteroid on Covid-19 Pneumonia Patients

Background: Globally over 704,753890 had COVID -19 Out of which 7,010,681 died compared to 12031 death in Nepal out of1003450 cases Nationwide. Corticosteroids because of their anti- inflammatory effect may have beneficial effect/s on COVID-19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. Corticosteroids are a potential therapeutic agent for patients with COVID-19 pneumonia. The RECOVERY (Randomised Trials in COVID-19 Therapy) trial provided data on the mortality benefits of corticosteroids. Aim: The study aims to see the effect of Corticosteroids on COVID-19 patient outcomes concerning disease progression, length of hospital stay, 28-day mortality, and use of resources like Ventilator. Method: Single Hospital-based Prospective observational study among RT-PCR positive for COVID-19 patients admitted at Kathmandu Medical College Teaching Hospital from June 01, 2021 –July 31st, 2021 requiring oxygen therapy. Patients were grouped into either usual care, including symptomatic treatment only, or a group receiving both usual care and Corticosteroid. Results: This study included 160 RT-PCR-positive cases. There were 53 patients with mild symptoms and 107 with moderate symptoms. Patients with mild symptoms who received standard care had an odds ratio of 1.875 for progression to moderate and severe COVID-19 Compared to those who received both standard care and corticosteroid. Similarly, Patients with moderate symptoms who received standard care had an odds ratio of 1.8 for progression to severe and critical COVID-19 Compared to those who received both standard care as well as corticosteroids. Among patients with mild symptoms, the overall use of a ventilator was 35.85 % and mortality was 13.21 %. Similarly, in patients with moderate symptoms at presentation, a ventilator was needed in 33.64 % and mortality was 24.30 %. Conclusion: Though Corticosteroids seem to have a beneficial role in preventing disease progression, they failed to show a statistically significant reduction of ventilator use and mortality benefit amongst groups.

Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea

BackgroundConflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD).MethodsA customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency’s COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure.ResultsData from 74,074 individuals with CLD was analyzed. The participants’ average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76–0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46–0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose.ConclusionsOur large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD.

A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19.

Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval, .96-1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73-1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted.Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.

An in-depth analysis of COVID-19 treatment: Present situation and prospects.

Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.

Hepatitis B Reactivation and Liver Failure Because of COVID-19 Infection

ABSTRACT Coronavirus disease 2019 (COVID-19) has been associated with liver injury incidence reported between 15% and 53%. Viral binding to ACE2 receptors in hepatobiliary cells is believed to cause liver inflammation. The relationship between hepatitis B and COVID-19 is poorly understood, but patients treated with immunosuppressive therapy for COVID-19 are at higher risk of hepatitis B reactivation (HBVr). We present a case of a patient with HBVr because of COVID-19, in the absence of any immunosuppressive treatment, leading to fulminant liver failure and subsequent requiring liver transplantation. Given low incidence, limited data, and no current guidelines, further studies are needed to evaluate the benefit and cost-effectiveness of anti-HBV prophylaxis in a patient with chronic hepatitis B (CHB) and COVID-19. Meanwhile, the American Association for the Study of Liver Diseases guidelines for patients with CHB and immunosuppressant use can be considered for anti-HBV prophylaxis for patients with CHB and COVID-19 to prevent HBVr on a case-by-case basis.

Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

Harnessing immunity: Immunomodulatory therapies in COVID-19.

An overly exuberant immune response, characterized by a cytokine storm and uncontrolled inflammation, has been identified as a significant driver of severe coronavirus disease 2019 (COVID-19) cases. Consequently, deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation. With these delicate dynamics in mind, immunomodulatory therapies have emerged as a promising avenue for mitigating the challenges posed by COVID-19. Precision in manipulating immune pathways presents an opportunity to alter the host response, optimizing antiviral defenses while curbing deleterious inflammation. This review article comprehensively analyzes immunomodulatory interventions in managing COVID-19. We explore diverse approaches to mitigating the hyperactive immune response and its impact, from corticosteroids and non-steroidal drugs to targeted biologics, including anti-viral drugs, cytokine inhibitors, JAK inhibitors, convalescent plasma, monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2, cell-based therapies (i.e., CAR T, etc.). By summarizing the current evidence, we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.

Outcomes of Obese Coronavirus 2019 Patients Treated with Extra Corporeal Membrane Oxygenation

Background: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is used as salvage therapy in severe cases of acute respiratory distress syndrome (ARDS) caused by the coronavirus disease 2019 (COVID-19). Obesity has been linked to worse disease severity and poor outcomes in COVID-19, but there is also a hypothesized obesity survival paradox whereby obese patients fare better in severe illness than their non-obese complement. The effect of obesity on ECMO outcomes in patients with COVID-19 is not well understood. Methods: We performed a retrospective analysis of all patients admitted to our institution who underwent VV ECMO cannulation for COVID-19 in the span of one year. These were separated by body mass index (BMI) with a cutoff of 35 kg/m2 (signifying class 2 obesity or higher) and compared with each other as well as a comparator group of patients with BMI >35 kg/m2 who underwent VV ECMO cannulation for any cause between 2016 and 1 March 2021. Disease severity was categorized using established scoring systems including Apache-II, Charleson-Dayeo, and Murray. Primary endpoints were 30 day mortality, survival to decannulation, and survival to discharge. Results: The study groups were similar in all respects with the exception of BMI. Illness severity, as classified by Charleson-Dayeo, Apache II, and Murray scores not significantly different between groups. The primary outcomes (30-day mortality, survival to decannulation, and survival to discharge) were not significantly different between groups. There was a trend toward more delayed inititation of ECMO therapy in the obese group that was not statistically significant. There was also a trend toward shorter duration of ECMO therapy that did not reach the threshold for statistical significance. Conclusions: There was no significant difference in outcomes between obese and non-obese patients undergoing VV ECMO for COVID-19. Trends toward shorter duration of ECMO and shorter intensive care unit (ICU) and hospital length of stay could represent the “obesity survival paradox” that has been described. Given similar outcomes, obesity should not be a contraindication to ECMO therapy for COVID-19.

Clinical characteristics and the risk factors for the exacerbation of symptoms in patients with inflammatory bowel disease during the COVID-19 pandemic.

In 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant caused a large-scale outbreak of coronavirus disease 2019 (COVID-19) in China. It is not clear the risk factors that lead to the exacerbation of symptoms in patients with inflammatory bowel disease (IBD) after COVID-19 infection. Our study aims to find out the risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection and to provide guidance for the clinical management of IBD. This is a retrospective, observational study. The online questionnaire was distributed to conduct a survey to collect demographic, clinical, and IBD related characteristics in IBD patients. Univariate and multivariate regression analyses were conducted to assess the independent effects. In total, 534 cases of IBD patients were analyzed in our study. Among them, 466 (87.3%) cases diagnosed with COVID-19, 160 (34.3%) cases experienced exacerbation of IBD symptoms, and 84 (18.0%) patients opted for medication discontinuation. Male sex (OR 2.04, 95% CI 1.34-3.49, p = 0.001), and the decrease in body mass index (BMI) (OR 0.93, 95% CI 0.87-1.00, p = 0.035) were positively correlated with the exacerbation of IBD symptoms. Furthermore, the medication discontinuation (OR 2.60, 95% CI 1.58-4.30, p < 0.001) was strongly positively correlated with the exacerbation of IBD symptoms. No significant association was seen between age, comorbidities, smoking, disease activity, vaccination, therapy for COVID-19 and the worsening of IBD symptoms. This study confirms that the infection rate of COVID-19 in China IBD patients was comparable to the general population. Male sex, the decrease in BMI and medication discontinuation are significant risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection.

Assessment of the potential interactions between favipiravir and radiocontrast agents

BACKGROUND In cases of coronavirus disease 2019 (COVID-19), favipiravir is commonly included to the therapy regimen. Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched. However, no research on possible drug interactions between Favipiravir and radiocontrast agents, which have become almost crucial in diagnostic processes while not being part of the treatment, has been found. AIM To determine potential medication interactions between Favipiravir and radiocontrast agents. METHODS The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) test while taking the medicine. The computerized patient files of the cases included in the study, as well as the pharmacovigilance forms in the designated hospital, were evaluated for this purpose. RESULTS The study included the evaluation of data from 1046 patients. The study sample's mean age was 47.23 ± 9.48 years. The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions (P = 0.003). When evaluated with logistic regression analysis, a 1-year raises in age increases the risk of developing drug interactions by 1.63 times (P = 0.023). There was no statistically significant difference in the occurrence of medication interactions between the sexes (P = 0.090). Possible medication interactions were discovered in 42 cases (4%). CONCLUSION The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values, as well as an increase in the frequency of nausea and vomiting. The majority of drug interactions discovered were modest enough that they were not reflected in the clinic. Drug interactions become more common as people get older.

Clinical efficacy of prophylactic intravenous immunoglobulin for elderly DLBCL patients with hypogammaglobulinemia in the COVID-19 pandemic era.

Elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population. A total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes. Among the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis. IVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG's potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies.

The GC-MS Analysis of Kabasura Kudineer: A Vital Siddha Drug in COVID-19 Therapy

ABSTRACT Introduction: This study focuses on the gas chromatography-mass spectrometry (GC-MS) analysis of Kabasura Kudineer, a Siddha formulation renowned for its properties against cold and exclusively utilized during the coronavirus disease 2019 (COVID-19) pandemic. Methods: The medication was obtained from a reputable Siddha vendor in Chennai, India, and subsequently extracted and subjected to GC-MS analysis. Results: The GC-MS profiling revealed the presence of several molecules, including benzoic acid, eugenol, alpha-ylangeneol, trans-2,4-dimethylthiane, S, S-dioxide, humulene, methyl 4,7,10,13-hexadecatetraenoate, 17-octadecynoic acid, 1-hexadecyn-3-ol, 3,7,11,15-tetramethyl, sulfurous acid, butyl heptadecyl ester, chloroacetic acid, tetradecyl ester, n-propyl cinnamate, oleyl alcohol, trifluoroacetate, 1-heptatriacotanol, and fenretinide. These compounds exhibit expansive medicinal roles. Conclusion: Kabasura Kudineer emerges as a highly effective remedy for cold-related ailments, particularly owing to the presence of bioactive compounds such as eugenol and humulene. These constituents play pivotal roles in antimicrobial and anti-inflammatory activities. Further investigations into the individual medicinal efficacy of each identified molecule are warranted to substantiate the therapeutic potential of Kabasura Kudineer, providing valuable insights for future applications.

Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches

ABSTRACT This study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset with control samples. Differential expression analysis identified 16 differentially expressed copper-death genes, and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) quantified immune cell infiltration. Gene classification yielded two copper-death clusters, with Weighted Gene Co-expression Network Analysis (WGCNA) identifying key module genes. Machine learning models (random forest, Support Vector Machine (SVM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost)) selected 6 feature genes validated by the GSE213313 dataset. Ferredoxin 1 (FDX1) emerged as the top gene, corroborated by Area Under the Curve (AUC) analysis. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed enriched pathways in T cell receptor, natural killer cytotoxicity, and Peroxisome Proliferator-Activated Receptor (PPAR). We uncovered differentially expressed copper-death genes and immune infiltration differences, notably CD8 T cells and M0 macrophages. Clustering identified modules with potential implications for COVID-19. Machine learning models effectively predicted COVID-19 risk, with FDX1‘s pivotal role validated. FDX1‘s high expression was associated with immune pathways, suggesting its role in COVID-19 pathogenesis. This comprehensive approach elucidated COVID-19-related copper-death genes, their immune context, and risk prediction potential. FDX1‘s connection to immune pathways offers insights into COVID-19 mechanisms and therapy.

The impact understanding of exosome therapy in COVID-19 and preparations for the future approaches in dealing with infectious diseases and inflammation

Cytokine storms, which result from an abrupt, acute surge in the circulating levels of different pro-inflammatory cytokines, are one of the complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess the effect of exosomes on the release of pro-inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19) and compare it with a control group. The cytokines evaluated in this study were TNF-α, IL-6, IL-17, and IFN-γ. The study compared the levels of these pro-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) of five COVID-19 patients in the intensive care unit, who were subjected to both inactivated SARS-CoV-2 and exosome therapy, with those of five healthy controls. The cytokine levels were quantified using the ELISA method. The collected data was analyzed in SPSS Version 26.0 and GraphPad Prism Version 9. According to the study findings, when PBMCs were exposed to inactivated SARS-CoV-2, pro-inflammatory cytokines increased in both patients and healthy controls. Notably, the cytokine levels were significantly elevated in the COVID-19 patients compared to the control group P-values were < 0.001, 0.001, 0.008, and 0.008 for TNF-α, IL-6, IL-17, and IFN-γ, respectively. Conversely, when both groups were exposed to exosomes, there was a marked reduction in the levels of pro-inflammatory cytokines. This suggests that exosome administration can effectively mitigate the hyperinflammation induced by COVID-19 by suppressing the production of pro-inflammatory cytokines in patients. These findings underscore the potential safety and efficacy of exosomes as a therapeutic strategy for COVID-19.

A single-center experience of COVID-19 infection in patients with primary immunodeficiency

Reported outcomes in patients with primary immunodeficiency (PID) infected by coronavirus disease 2019 (COVID-19) have been variable owing to a combination of viral strain heterogeneity, differences in patient populations and health systems, and local availability of vaccination and specific COVID-19 therapies. There are few reports on the experience of Australian patients with PID during the pandemic. In this retrospective study, we describe the baseline characteristics and short-term outcomes of patients with PID who were infected by COVID-19 and known to the Royal Melbourne Hospital, a major tertiary center in Victoria, Australia. Between April 2021 and April 2022, a total of 31 of 138 patients with PID were affected by COVID-19. More than half of them had 3 vaccine doses at the time of infection (which at the time was considered being fully vaccinated) and received COVID-19-targeted treatment. All of the infected patients had ambulatory disease, with no cases of morbidity or mortality. In line with the current literature, the PID subtypes described did not appear to independently predict worse outcomes. Some protective factors include this cohort's relatively younger average age and its high uptake of vaccination and COVID-19 therapies.

Medication adherence of cardiovascular patients after COVID-19: 6-month follow-up

Aim. To evaluate the relationship of various factors with adherence to therapy in cardiovascular patients after a coronavirus disease 2019 (COVID-19).Material and methods. The study included 284 patients (inpatients — 176, outpatients — 108) with cardiovascular diseases (hypertension, heart failure (HF), coronary artery disease, atrial fibrillation) after COVID-19. We collected data on cardiovascular history, made a questionnaire survey about COVID-19 course (symptoms, their severity, self-assessment of the disease severity). Paraclinical diagnostic investigations were carried out. In addition, 1, 3, 6 months after recovery, all respondents were invited for examination, laboratory tests, and survey using the Hospital Anxiety and Depression Scale (HADS). Cardiovascular therapy adherence was assessed at 1, 3 and 6 months after recovery and adherence to COVID-19 treatment 1 month after inclusion in the study by comparing the compliance of the drugs prescribed at discharge with its actual use.Results. In total, 212 respondents continued study participation after 1 month, while 64,2% were adherent to cardiovascular therapy and 56,6% — to COVID-19 therapy. Compliance at 3 and 6 months was 60,4% (n=212) and 52,8% (n=188), respectively. A moderate correlation was found between adherence to treatment and the persistence of apprehension 1 month after recovery (r=0,33, p&lt;0,05), moderate or severe weakness during disease (r=0,31, p&lt;0,05), COVID-19 severity (r=0,39, p&lt;0,05). Inhospital respondents with lung tissue involvement &gt;25% (n=64, 36,4%) were more adherent to standard cardiovascular therapy, prescribed in accordance with clinical guidelines (r=0,336, p&lt;0,05). Adverse events in the form of a hypertensive crisis, arrhythmias, decompensated HF 1, 3, 6 months after recovery significantly increased the compliance with medical recommendations (p&lt;0,05). Medication adherence regarding COVID-19 was associated with the disease severity, HF history, apprehension and anxiety, weakness, and decreased exercise tolerance (p&lt;0,05).Conclusion. After 1 month, adherence to cardiovascular and COVID-19 therapy did not differ significantly (p&gt;0,05). Compliance after 1, 3, 6 months was positively influenced by COVID-19 severity, the subjective feeling of weakness, apprehension and anxiety during disease and the persistence of a subjective feeling of anxiety after recovery. Adverse events (hypertensive crisis, arrhythmia, decompensated HF) during 1, 3 and 6 months after COVID-19 significantly (p&lt;0,05) increased adherence to treatment.

Low-dose radiation therapy for COVID-19

Background. Radiation therapy is one of the most effective treatments in patients with malignant neoplasms, it also plays an important role in the treatment of non-oncological di­seases. The coronavirus disease 2019 (COVID-19) pandemic has prompted a review of the long-forgotten idea of using low-dose radiation therapy (LDRT) in patients with lobar and interstitial pneumonia. Historically, from 1905 to the mid-1940s, LDRT was used to treat pneumonia, and evidence suggests that it might improve survival and provide rapid relief of respiratory symptoms. The purpose was to summarize current information about ­using low-dose radiation therapy in the treatment of patients with ­COVID-19. Materials and methods. A selection of publications was carried out, which covered information on the possibilities of using low-dose radiation therapy in the treatment of patients with COVID-19. At the first stage, a search was conducted for lite­rary sources using the keywords: COVID-19, low-dose radiation therapy. At the second stage, summaries of articles were studied and publications that did not meet the research criteria were excluded. At the third stage, the full texts of the selected articles were studied for compliance with the criteria for inclusion in the reference list and research relevance. Results. As of August 1, 2023, according to ClinicalTrials.gov, among 9,244 clinical trials associated with COVID-19, sixteen are currently being conduc­ted. They examine the effectiveness of LDRT in the treatment of patients with COVID-19 and already involve 1,038 patients. The largest number of studies is conducted in European countries. It has been shown that LDRT selectively attenuates oxidative stress to an inflammatory stimulus and inhibits the nitric oxide production pathway. This may contribute to its anti-inflammatory and vascular effects. At the same time, heme oxygenase 1 and other antioxidants are induced, they are mediated by Nrf2, which is the main regulator of endogenous antioxidant, anti-stress, analgesic reactions, and is also closely related to nicotinamide adenine dinucleotide phosphate and the metabolic pathway of pentose phosphate. Nrf2 may be critical for pain relief associated with edema formation and possibly plays a major role in the effects of LDRT, whereas direct functional effects of low-dose radiation on the autonomic nervous system and nociception are likely to be smaller. Conclusions. From 1905 to 1946, researchers published the results of more than 15 clinical studies on the effectiveness of radiotherapy for inflammatory lung diseases, which included more than 850 patients and demonstrated the high therapeutic effectiveness of radiation therapy in the indicated pathology. Today, there are 16 ongoing clinical trials in the world devoted to the study of LDRT effectiveness in the treatment of patients with COVID-19, in which 1,038 patients have already been involved. The risk of radiation-induced lung and breast cancer in a 25-year-old woman exposed to 1 Gy whole chest radiation may be as high as 5.9 and 5.5 %, respectively.

Knee osteonecrosis after SARS-CoV-2 infection: a systematic case-based review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19). Patients with COVID-19 manifested symptoms mainly related to the respiratory system, but also the musculoskeletal system can be involved. COVID-19 has been described as a possible cause of knee osteonecrosis (ON). A systematic review was performed to investigate the hypothetical correlation between COVID-19 and knee ON. Inclusion criteria were all articles reporting cases of knee ON after a diagnosis of SARS-CoV-2 infection. Considering that COVID-19 is an emerging disease, all levels of evidence studies were included. Finally, two case series and three case reports were included. We extracted data regarding demographic and clinical characteristics, details of magnetic resonance imaging (MRI), use of corticosteroids (CCS), temporal correlation between ON and COVID-19, treatment of the lesion and its outcomes. A total of seven cases of post-COVID knee ON have been described. Knee pain arose on average 11 weeks after the diagnosis of COVID-19. All patients had knee MRI showing ON. CCS were used to treat COVID-19-related symptoms in four cases. Conservative treatment was successful in five patients. The correlation between COVID-19 and ON remains unclear. Probably post-COVID-19 ON has a multifactorial origin in which factors related to the patient, consequences of COVID-19 and CCS therapy add up to cause a reduction of blood supply and bone vitality until ON is triggered. A greater number of patients is needed to clarify the role of COVID-19 in the etiopathogenesis of knee ON.