Severe Acute Respiratory Syndrome Virus Research Articles

SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression.

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

Genome Monitoring of SARS-CoV-2 Circulating in the Kyrgyz Republic in 2020–2021

Introduction: The RNA-containing severe acute respiratory syndrome virus SARS-CoV-2 has spread rapidly around the world by adaptation to the host through genetic evolution. The emergence of variants with genetic mutations that increase contagiousness and transmission may hamper the effectiveness of disease control programs and efficacy of vaccination. Objective: To establish dominant SARS-CoV-2 variants circulating in the Kyrgyz Republic in 2020–2021. Materials and methods: Genomic monitoring was carried out based on positive results of testing nasopharyngeal swabs. SARS-CoV-2 was detected by a real-time reverse transcription –polymerase chain reaction (RT-PCR) assay using registered commercial test kits. Genetic variants (n = 15) were determined by high-throughput sequencing on a MiSeq device (Illumina, USA) using the COVID-19 ARTIC v3 protocol. Mutational variability of SARS-CoV-2 was examined using a cluster analysis of amino acid substitutions in the S protein using Ward’s method. Nucleotide sequences from Kyrgyzstan (n = 15), Russia (n = 16), India (n = 2), and China (n = 2) were aligned using MAFFT. IQ-TREE v1.6.12 was used to infer the phylogenetic tree by maximum likelihood applying Nextstrain processes. Isolates Wuhan/Hu-1/2019 and Wuhan/WH01/2019 downloaded from the GenBank® database were considered to be the root of the tree (reference). Results: Phylogenetic data analysis revealed that SARS-CoV-2 B.1.1.7 (Alpha) was the dominant VOC variant, the proportion of which was as high as 36.4 % (12/33); B.1.351 (Beta) was also found (6.1 % or 2/33). When samples were examined for amino acid substitutions in the S-protein, B.1.1.7 Alpha (British) isolates were found to cluster into two distinct branches. Conclusion: The study of the frequency and influence of mutations on pathogenetic properties of the virus, as well as the analysis of the predominant variants of the virus will allow timely measures to be taken to counteract the spread of SARS-CoV-2 in the country. In this regard, continuous genome monitoring of circulating COVID-19 variants is necessary.

Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease

Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary heart disease in comparison to healthy individuals. The downregulation of miR-19a/b has been observed to facilitate the replication of influenza A virus (IAV). miR-19a/b can effectively inhibit IAV replication by targeting and reducing the expression of SOCS1, as observed in cell-based and coronary heart disease mouse models. This mechanism leads to the alleviation of the inhibitory effect of SOCS1 on the interferon (IFN)/JAK/STAT signaling pathway. The results indicate that the IAV employs a unique approach to inhibit the host's type I IFN-mediated antiviral immune responses by decreasing miR-19a/b. These findings provide additional insights into the underlying mechanisms of susceptibility to flu in patients with coronary heart disease. miR-19a/b can be considered as a preventative/therapy strategy for patients with coronary heart disease against influenza virus infection.

The Association Between Genetic Variants in ACE1and ACE2 Genes with Susceptibility to COVID-19 Infection.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Overview of COVID-19 Infection, Treatment, and Prevention in Children.

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.

Cryptococcus laurentii: A rare and serious fungal infection, and a rising cause of concern in post-COVID-19 era

Coronaviruses are a large group of viruses that infect humans and animals. Rarely, coronaviruses that infect animals can evolve and infect humans and spread between them. Current evidence for coronavirus disease-2019 (COVID-19) suggests that the causative virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a strain of coronavirus that causes COVID-19, the respiratory illness responsible for COVID-19 pandemic, has a zoonotic origin, closely related to the bat-origin SARS-like coronavirus. The present case report describes the case of a 63-year-old male patient who presented with post-COVID-19 symptoms including fever, and was later diagnosed positive for Cryptococcus laurentii on a urine culture sensitivity test. The following core competencies are addressed in this article: Practice-based learning and improvement, Patient care and procedural skills, Medical knowledge.

The relationship between body mass index and mortality is not linear in patients requiring venovenous extracorporeal support

ObjectiveMorbid obesity may influence candidacy for venovenous extracorporeal membrane oxygenation (VVECMO) support. Indeed, body mass index (BMI) >40 is considered to be a relative contraindication due to increased mortality observed in patients with BMI above this value. There is scant evidence to characterize this relationship beyond speculating about the technical challenges of cannulation and difficulty in optimizing flows. We examined a national cohort to evaluate the influence of BMI on mortality in patients requiring VVECMO for severe acute respiratory syndrome coronavirus 2 infection. MethodsWe performed a retrospective cohort analysis on National COVID Cohort Collaborative data evaluating 1,033,229 patients with BMI ≤60 from 31 US hospital systems diagnosed with severe acute respiratory syndrome virus coronavirus 2 infection from September 2019 to August 2022. We performed univariate and multivariable mixed-effects logistic regression analysis on data pertaining to those who required VVECMO support during their hospitalization. A subgroup risk-adjusted analysis comparing ECMO mortality in patients with BMI 40 to 60 with the 25th, 50th, and 75th BMI percentile was performed. Outcomes of interest included BMI, age, comorbidity score, body surface area, and ventilation days. ResultsA total of 774 adult patients required VVECMO. Of these, 542 were men, median age was 47 years, mean adjusted Charlson Comorbidity Index was 1, and median BMI was 33. Overall mortality was 47.8%. There was a nonsignificant overall difference in mortality across hospitals (SD, 0.31; 95% CI, 0-0.57). After mixed multivariable logistic regression analysis, advanced age (P < .0001) and Charlson Comorbidity Index (P = .009) were each associated with increased mortality. Neither gender (P = .14) nor duration on mechanical ventilation (P = .39) was associated with increased mortality. An increase in BMI from 25th to 75th percentile was not associated with a difference in mortality (P = .28). In our multivariable mixed-effects logistic regression analysis, there exists a nonlinear relationship between BMI and mortality. Between BMI of 25 and 32, patients experienced an increase in mortality. However, between BMI of 32 and 37, the adjusted mortality in these patients subsequently decreased. Our subgroup analysis comparing BMIs 40 to 60 with the 25th, 50th, and 75th percentile of BMI found no significant difference in ECMO mortality between BMI values of 40 and 60 with the 25th, 50th, 75th percentile. ConclusionsAdvancing age and higher CCI are each associated with increased risk for mortality in patients requiring VVECMO. A nonlinear relationship exists between mortality and BMI and those between 32 and 37 have lower odds of mortality than those between BMI 25 and 32. This nonlinear pattern suggests a need for further adjudication of the contraindications associated with VVECMO, particularly those based solely on BMI.

Long-COVID is Associated with Impaired Red Blood Cell Function.

COVID-19 disease, caused by the severe acute respiratory syndrome virus 2 (SARS-CoV-2), induces a broad spectrum of clinical symptoms ranging from asymptomatic cases to fatal outcomes. About 10-35% of all COVID-19 patients, even those with mild COVID-19 symptoms, continue to show symptoms, i. e., fatigue, shortness of breath, cough, and cognitive dysfunction, after initial recovery. Previously, we and others identified red blood cell precursors as a direct target of SARS-CoV-2 and suggested that SARS-CoV-2 induces dysregulation in hemoglobin- and iron-metabolism contributing to the severe systemic course of COVID-19. Here, we put particular emphasis on differences in parameters of clinical blood gas analysis and hematological parameters of more than 20 healthy and Long-COVID patients, respectively. Long-COVID patients showed impaired oxygen binding to hemoglobin with concomitant increase in carbon monoxide binding. Hand in hand with decreased plasma iron concentration and transferrin saturation, mean corpuscular hemoglobin was elevated in Long-COVID patients compared to healthy donors suggesting a potential compensatory mechanism. Although blood pH was within the physiological range in both groups, base excess- and bicarbonate values were significantly lower in Long-COVID patients. Furthermore, Long-COVID patients displayed reduced lymphocyte levels. The clinical relevance of these findings, e. g., as a cause of chronic immunodeficiency, remains to be investigated in future studies. In conclusion, our data suggest impaired erythrocyte functionality in Long-COVID patients, leading to diminished oxygen supply. This in turn could be an explanation for the CFS, dyspnea and anemia. Further investigations are necessary to identify the underlying pathomechanisms.

Role of Toll-like receptor gene polymorphism in pathogenesis of new coronavirus infection

The review article contains data from literature which concern the role of Toll-like receptors (TLRs), immune sensors that play a key role in the systemic response to both bacterial and viral infections, e.g., in pathogenesis of a new coronavirus infection (COVID-19, SARS-CoV-2 infection). With advent of COVID-19, which has reached the scale of a pandemic, the interest in studying predictive factors for the severity of the infectious process has acquired a new cycle. The previous epidemics caused by severe acute respiratory syndrome virus (SARS-CoV), as well as the Middle East respiratory syndrome coronavirus (MERS-CoV), helped us to understand the degree of immune response in these conditions, as well as to suggest medical approaches to the pathogens of this family, i.e., which measures should be taken, and what long-term forecasts may be encountered for the SARS-CoV-2 outbreaks. Each of the 10 human TLRs recognizes a specific structure within a bacterial / viral or fungal pathogen. The effect on TLR activates the inflammatory signaling cascade via mediators, i.e., intracellular TIR domains mediated by adapter proteins. These reactions lead to the production of the most important antiviral response substances. The factors that lead to reduced / increased expression of TLR genes include gene polymorphisms which control the functioning of the immune system in some ways, thus causing a reduced, or hyperinflammatory response to an infectious agent. Genetic heterogeneity is likely to explain, at least partially, the wide range of clinical manifestations of COVID-19 infection in general population. Therefore, there is an increased interest in studies of these receptors, the degree of their expression throughout the infectious process, the polymorphisms of the TLR-encoding genes, and, consequently, the opportunity of using clinical and laboratory tests for their qualitative and quantitative assessment, as well as selection and prospects of further treatment in each personal case.

Antiviral efficacy of nanomaterial-treated textiles in real-life like exposure conditions

Due to the growing interest towards reducing the number of potentially infectious agents on critical high-touch surfaces, the popularity of antimicrobially and antivirally active surfaces, including textiles, has increased. The goal of this study was to create antiviral textiles by spray-depositing three different nanomaterials, two types of CeO2 nanoparticles and quaternary ammonium surfactant CTAB loaded SiO2 nanocontainers, onto the surface of a knitted polyester textile and assess their antiviral activity against two coronaviruses, porcine transmissible gastroenteritis virus (TGEV) and severe acute respiratory syndrome virus (SARS CoV-2). Antiviral testing was carried out in small droplets in semi-dry conditions and in the presence of organic soiling, to mimic aerosol deposition of viruses onto the textiles. In such conditions, SARS CoV-2 stayed infectious at least for 24 h and TGEV infected cells even after 72h of semi-dry deposition suggesting that textiles exhibiting sufficient antiviral activity before or at 24 h, can be considered promising. The antiviral efficacy of nanomaterial-deposited textiles was compared with the activity of the same nanomaterials in colloidal form and with positive control textiles loaded with copper nitrate and CTAB. Our results indicated that after deposition onto the textile, CeO2 nanoparticles lost most of their antiviral activity, but antiviral efficacy of CTAB-loaded SiO2 nanocontainers was retained also after deposition. Copper nitrate deposited textile that was used as a positive control, showed relatively high antiviral activity as expected. However, as copper was effectively washed away from the textile already during 1 h, the use of copper for creating antiviral textiles would be impractical. In summary, our results indicated that antiviral activity of textiles cannot be predicted from antiviral efficacy of the deposited compounds in colloid and attention should be paid on prolonged efficacy of antivirally coated textiles.

Humoral immunity against SARS-CoV-2 evoked by heterologous vaccination groups using the CoronaVac (Sinovac) and BNT162b2 (Pfizer/BioNTech) vaccines in Chile.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.

COVID-19 activity risk calculator as a gamified public health intervention tool

The Coronavirus disease 2019 (COVID-19) pandemic, caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted over 200 countries leading to hospitalizations and deaths of millions of people. Public health interventions, such as risk estimators, can reduce the spread of pandemics and epidemics through influencing behavior, which impacts risk of exposure and infection. Current publicly available COVID-19 risk estimation tools have had variable effectiveness during the pandemic due to their dependency on rapidly evolving factors such as community transmission levels and variants. There has also been confusion surrounding certain personal protective strategies such as risk reduction by mask-wearing and vaccination. In order to create a simple easy-to-use tool for estimating different individual risks associated with carrying out daily-life activity, we developed COVID-19 Activity Risk Calculator (CovARC). CovARC is a gamified public health intervention as users can ”play with” how different risks associated with COVID-19 can change depending on several different factors when carrying out routine daily activities. Empowering the public to make informed, data-driven decisions about safely engaging in activities may help to reduce COVID-19 levels in the community. In this study, we demonstrate a streamlined, scalable and accurate COVID-19 risk calculation system. Our study also demonstrates the quantitative impact of vaccination and mask-wearing during periods of high case counts. Validation of this impact could inform and support policy decisions regarding case thresholds for mask mandates, and other public health interventions.

The Effect of SARS-CoV-2 İnfection on Perinatal Outcomes in Hypertensive Disorders of Pregnancy.

To evaluate the fetal and maternal effects of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in women with hypertensive disorders of pregnancy. Patients with hypertensive disorders of pregnancy and SARS-CoV-2 polymerase chain reaction (PCR) positivity (n = 55) were compared with cases with similar characteristics and PCR negativity (n = 53). The study group was further divided into two groups as severe (n = 11) and nonsevere (n = 44) coronavirus disease 2019 (COVID-19). The groups were compared in terms of clinical characteristics and perinatal outcomes. The study and control groups were similar in terms of maternal age, parity, gestational age at diagnosis, type of hypertensive disorders, magnesium sulfate administration rate, gestational age at birth, birth weight, Apgar scores, and maternal complications. However, all cases of fetal loss (n = 6) were observed in the SARS-CoV-2 positive group (p = 0.027). From the 6 cases, there were 5 in the nonsevere group and 1 patient in the severe SARS-CoV-2 positive group. Moreover, higher rates of maternal complications, lower oxygen saturation values, and intensive care unit admissions were observed in the severe COVID-19 group. Physicians should be cautious about the management of hypertensive disorders of pregnancy cases with SARS-CoV-2 positivity. Fetal loss seems to be more common in cases with SARS-CoV-2 positivity and severe COVID-19 seems to be associated with higher rates of maternal complications. Close follow-up for fetal wellbeing and active management of severe cases in terms of maternal complications seem to be favorable.

Seroprevalence of SARS-CoV-2(Covid-19) Antibody Among Blood Donors in a Tertiary Care Centre in South India

Introduction The novel severe acute respiratory syndrome virus 2 (SARS-CoV-2), which is responsible Coronavirus disease (COVID-19), spread worldwide from China, causing a pandemic from late December 2019. Due to the high proportion of asymptomatic or mild infections (approximately 80%), data restricted to laboratory-confirmed cases do not capture the true extent of the spread or burden of the virus, or its infection-fatality ratio. Therefore, serological detection of specific antibodies against SARS-CoV-2 can better estimate the true number of infections. The current study aims to estimate the seroprevalence of SARS-CoV-2 antibodies among the whole blood donors without any prior COVID-19 history or symptoms. Objective To determine seroprevalence of SARS-CoV-2 (COVID-19) antibody (IgG and IgM) among asymptomatic healthy blood donors. Methods This was a cross sectional study conducted between March and July, 2021 among 300 blood donors without any prior COVID-19 history or symptoms who came to a tertiary care, multispecialty hospital in south India. Any donor who had recently travelled abroad or donors who had received COVID-19 vaccine are excluded from the study. 3 ml venous blood was drawn in EDTA tube from participants and was tested by “Access SARS CoV-2 IgG assay” and “Access SARS CoV-2 IgM assay” by UniCel DxI 800 Immunoassay analyzer (Beckman coulter). The Access SARS CoV-2 IgG assay and the Access SARS Cov-2 IgM assay detect antibodies to the Receptor Binding Domain (RBD) of the Spike Protein. Result was reported as Reactive if Signal/Cut-off (S/CO)&gt;1.0 and non-Reactive if S/CO &lt;1. Data was collected and entered into excel sheets and was analyzed by using the software SPSS version 25. Results A total of 300 healthy blood donors were included. The study reported seroprevalence of 15.3% for IgG and 4.3% for IgM (95%CI) among asymptomatic whole blood donors. No significant difference was observed across age groups, diet, BMI, ABO/Rh blood type or Ayurveda/homeo immune medicine intake with respect to IgG and IgM reactivity. Conclusion 15% of blood donors were seroconverted for COVID-19 during second wave. This reflects widespread seroprevalence in the adult population. Real-time seroprevalence studies will help to know the herd immunity among the blood donors which will assist in knowing the COVID-19 transmission dynamics and distribution of immunity levels at a particular point in time.

A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections.

Antibody Dependent Enhancement (ADE) of an infection has been of interest in the investigation of many viruses. It is associated with the severity of the infection. ADE is mediated by non-neutralizing antibodies, antibodies at sub-neutralizing concentrations, or cross-reactive non-neutralizing antibodies. Treatments like plasma therapy, B cell immunizations, and antibody therapies may trigger ADE. It is seen as an impediment to vaccine development as well. In viruses including the Dengue virus (DENV), severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus, human immunodeficiency virus (HIV), Ebola virus, Zika virus, and influenza virus, the likely mechanisms of ADE are postulated and described. ADE improves the likelihood of productively infecting cells that are expressing the complement receptor or the Fc receptor (FcR) rather than the viral receptors. ADE occurs when the FcR, particularly the Fc gamma receptor, and/or complement system, particularly Complement 1q (C1q), allow the entry of the virus-antibody complex into the cell. Moreover, ADE alters the innate immune pathways to escape from lysis, promoting viral replication inside the cell that produces viral particles. This review discusses the involvement of FcR and the downstream immunomodulatory pathways in ADE, the complement system, and innate antiviral signaling pathways modification in ADE and its impact on facilitating viral replication. Additionally, we have outlined the modes of ADE in the cases of different viruses reported until now.

Clinical efficacy of the fourth dose of the BNT162b2 vaccine in maintenance dialysis patients.

Highly effective vaccines against severe acute respiratory syndrome virus 2 have been developed and administered worldwide. However, protection from coronavirus disease 2019 is not absolute and an optimal vaccination regimen needs to be established. This study assessed the clinical efficacy of the coronavirus disease 2019 vaccine among dialysis patients receiving 3 or 4 doses of vaccine. This retrospective study was conducted using the electronic database of Clalit Health Maintenance Organization in Israel. Chronic dialysis patients treated with either hemodialysis or peritoneal dialysis during the coronavirus disease 2019 pandemic were included. We compared clinical outcomes of patients who had received three or four doses of the severe acute respiratory syndrome virus 2 vaccine. This study included 1,030 patients on chronic dialysis,with a mean age of 68 ± 13years. Among them, 502 patients had received 3 doses of the vaccine and 528 received 4 doses. Severe acute respiratory syndrome virus 2 infection rates, severe COVID-19 that resulted in hospitalizations, COVID-19-related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after controlling for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, the fourth dose was significantly associated with reduced COVID-19-related mortality (1.7% vs. 3.8%, p = 0.04). Odds ratio for COVID-19-related mortality was 0.44 with 95% CI 0.2-0.98. As seen in the general population and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19-related hospitalization and mortality among chronic dialysis patients. Further studies are needed to establish the optimal regimens of vaccination for patients on chronic dialysis.

The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm-A Powerful Therapeutic Tool for COVID-19 Patients.

Currently, there is still no effective and definitive cure for the coronavirus disease 2019 (COVID-19) caused by the infection of the novel highly contagious severe acute respiratory syndrome virus (SARS-CoV-2), whose sudden outbreak was recorded for the first time in China in late December 2019. Soon after, COVID-19 affected not only the vast majority of China's population but the whole world and caused a global health public crisis as a new pandemic. It is well known that viral infection can cause acute respiratory distress syndrome (ARDS) and, in severe cases, can even be lethal. Behind the inflammatory process lies the so-called cytokine storm (CS), which activates various inflammatory cytokines that damage numerous organ tissues. Since the first outbreak of SARS-CoV-2, various research groups have been intensively trying to investigate the best treatment options; however, only limited outcomes have been achieved. One of the most promising strategies represents using either stem cells, such as mesenchymal stem cells (MSCs)/induced pluripotent stem cells (iPSCs), or, more recently, using cell-free approaches involving conditioned media (CMs) and their content, such as extracellular vesicles (EVs) (e.g., exosomes or miRNAs) derived from stem cells. As key mediators of intracellular communication, exosomes carry a cocktail of different molecules with anti-inflammatory effects and immunomodulatory capacity. Our comprehensive review outlines the complex inflammatory process responsible for the CS, summarizes the present results of cell-free-based pre-clinical and clinical studies for COVID-19 treatment, and discusses their future perspectives for therapeutic applications.

#4774 THE USE OF REGDANVIMAB FOR THE PREVENTION OF SEVERE COVID-19 IN PATIENTS ON HEMODIALYSIS

Abstract Background and Aims A new coronavirus infection has become a serious threat leading to increased mortality worldwide. COVID-19 is an acute airborne disease caused by severe acute respiratory syndrome virus (SARS-Cov-2). Evolution of the virus, emergence of new mutant strains, changes in virulence dictate the need to search for new tools both in treatment and prevention of severe disease. The aim of our study was evaluation of the efficacy of Regdanvimab (Regkirona, Samsung BioLogics) to prevent severe COVID-19 in patients receiving ambulatory hemodialysis in the period of increasing morbidity. Method The study included 20 patients on program hemodialysis, mean age 54.9±17.6 years, vaccinated or who underwent COVID-19 more than six months ago. All subjects of the study received Regkirona at a standard dose of 40 mg/kg of body weight intravenously once at the end of the hemodialysis procedure after the physician assessed the feasibility of prophylaxis. All subjects were assessed for humoral immunity before Regkirona administration and after Regkirona administration according to the level of total SARS-CoV-2 IgG and IgG antibodies to the subunit of the S1 receptor-binding domain of the SARS-CoV-2 protein. Results Total SARS-CoV-2 IgG level and IgG level of antibodies to SARS-CoV-2 receptor-binding subunit S1 was 83.9±69.5 U/ml and 260.7±199.5 BAU/ml respectively before drug administration. During the 6-month follow-up period from July to November 2022, which paralleled the next round of increased morbidity, four patients with SARS-CoV-2 PCR test positive reported mild to moderate symptoms of SARS (marked weakness, fever, loss of smell, catarrhal symptoms, cough, shortness of breath, and chest pain unassociated with other causes). None of the subjects required hospitalization. We evaluated IgG antibody titers to the receptor-binding domain of the SARS-CoV-2 protein subunit S1 after 1, 3 and 6 months and demonstrated a nonlinear decline titers from 5104±2257.1 BAU/ml, 1988.7±1440.4 BAU/ml to 407,0±350,2 BAU/ml respectively, which may indirectly reflect short half-life of Regkirona. Conclusion The results of our study showed the efficacy of Regdanvimab to prevent the severe disease of COVID-19 in high-risk patients during the period of rising morbidity.

#3161 CLINICAL EFFICACY AND OPTIMAL REGIMEN OF BNT162B2 VACCINE IN CHRONIC DIALYSIS PATIENTS

Abstract Background and Aims Highly effective vaccines against severe acute respiratory syndrome virus 2 (SARS-CoV-2) have been developed and administered worldwide. Protection from coronavirus disease 2019 (COVID-19), however, is not absolute, and optimal vaccination regimens need to be established. Concerns regarding breakthrough COVID-19 disease in vaccinated patients are increasing, as vaccine efficacy appears to gradually decline in the months following vaccination. The emergence of highly infective variants, escalates these issues. This study assessed the clinical efficacy of the BNT162b2 vaccine and all-cause mortality among dialysis patients receiving varying numbers of vaccine doses. Method This study was conducted using the electronic database of Clalit Health Services in Israel. Patients receiving chronic hemodialysis or peritoneal dialysis during COVID-19 pandemic were included in the analysis. The control group consisted of age-and sex-matched individuals, in a 4:1 ratio to the dialysis group. The study included the pre- and post-vaccination periods. Results A total of 14,230 people were included; 2,846 on chronic dialysis and 11,384 controls. Mean age was 66.2±14.3 years (range 18-97). Before the vaccine was available in Israel, 223 dialysis patients were infected with SARS-CoV2. Their mortality rate was 18.4% compared to 10.8% among uninfected, unvaccinated patients in the same period (p = 0.001). On post-vaccination period, we compared the clinical efficacy of a fourth dose to patients who received only 3 doses of BNT162b2 vaccine. SARS-CoV-2 infection rates, hospitalizations due to severe COVID-19, COVID-19–related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after adjusting for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, an additional booster dose was associated with reduced COVID-19–related mortality (1.7% vs. 3.8%, p = 0.04, HR 0.44 (95% CI 0.2–0.98) in patients who received 4 doses compared to 3 doses. Conclusion As seen in the general population, and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19 hospitalization and mortality among chronic dialysis patients. This study strengthens the recommendation to administer a fourth booster dose of vaccine to dialysis patients. Further studies are needed to establish the exact dose and schedule of the COVID-19 vaccine in the vulnerable population patients on chronic maintenance dialysis.

COVID-19 in Western Australia: 'The last straw' and hopes for a 'new normal' for parents of children with long-term conditions.

Children with long-term conditions are vulnerable due to the treatments required for their conditions. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, Western Australians experienced restrictions that changed daily life activities but were able to return to some of their previous routines due to the restrictions. The study explored the stress experiences of parents caring for children with long-term conditions during COVID-19 in Western Australia. The study was codesigned with a parent representative caring for children with long-term conditions to ensure essential questions were targeted. Twelve parents of children with various long-term conditions were recruited. Ten parents completed the qualitative proforma, and two parents were interviewed in November 2020. Interviews were audio-recorded and transcribed verbatim. Data were anonymised and analysed using reflexive thematic analysis. Two themes were produced: (1) 'Keep my child safe' describes the children's vulnerabilities due to their long-term conditions, the adjustments parents' made to keep their children safeand the various consequences faced. (2) 'COVID-19's silver lining' covers the positives of the COVID-19 pandemic, including their children having fewer infections, the availability of telehealth appointments, relationship improvements and the parent's hopes for a new normal where behaviours prevent transmission of infectious (e.g., hand sanitising). Western Australia provided a unique context for the COVID-19 pandemic due to no transmission of the virus severe acute respiratory syndrome coronavirus 2 at the time of the study. The tend and befriend theory aids in explaining the parents' stress experiences, and the application highlights a unique aspect of this theory. Parents tended to their children during COVID-19, but many could no longer rely on others for connection, support and respite, and became further isolated in attempting to protect their children due to COVID-19 consequences. The findings highlight that some parents of children with long-term conditions need specific attention during times of pandemics. Further review is recommended to support parents through the impact of COVID-19 and similar crises. This study was codesigned with an experienced parent representative who was part of the research team and involved throughout the research process to ensure meaningful end-user engagement and ensure essential questions and priorities were addressed.