Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study.

Background and objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions. Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method. Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value. Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size.

The use of human iPSC-derived alveolar organoids to explore SARS-CoV-2 variant infections and host responses.

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development. AOs express alveolar epithelial type II cell protein markers including pro-surfactant protein C and ATP binding cassette subfamily A member 3. Compared to primary human alveolar type II cells, AOs expressed higher mRNA levels of SARS-CoV-2 entry factors, angiotensin-converting enzyme 2 (ACE2), asialoglycoprotein receptor 1 (ASGR1) and basigin (CD147). Considering the localization of ACE2 on the apical side in AOs, we used three AO models, apical-in, sheared and apical-out for SARS-CoV-2 infection. All three models of AOs were robustly infected with the SARS-CoV-2 irrespective of ACE2 accessibility. Antibody blocking experiment revealed that ASGR1 was the main receptor for SARS-CoV2 entry from the basolateral in apical-in AOs. AOs supported the replication of SARS-CoV-2 variants WA1, Alpha, Beta, Delta, and Zeta and Omicron to a variable degree with WA1 being the highest and Omicron being the least. Transcriptomic profiling of infected AOs revealed the induction of inflammatory and interferon-related pathways with NF-κB signaling being the predominant host response. In summary, iPSC-derived AOs can serve as excellent human lung models to investigate infection of SARS-CoV-2 variants and host responses from both apical and basolateral sides.

Convalescent plasma transfusion for immunocompromised viremic patients with COVID-19: A retrospective multicenter study.

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

Changes in Treatment Conditions for Patients Receiving Hemodialysis at Nippon Medical School Hospital during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has had an enormous impact on hemodialysis patients. This study investigated changes in hemodialysis treatment at our hospital after the start of the pandemic. METHODS: We analyzed data from the Diagnosis Procedure Combination (DPC) system. Data for inpatients receiving dialysis during collection periods A (before the COVID-19 pandemic) and B (after the start of the COVID-19 pandemic) were extracted and compared. The numbers of inpatients and new patients, the number of patients admitted (by department), duration of stay, mortality, place of residence, surgical procedures, and DPC classification were compared. RESULTS: There were no significant differences between periods in patient age, duration of hospital stay, number of new patients, number of ambulance transports, number of deaths, body mass index, comorbidities, laboratory variables before the first dialysis after hospitalization, or patient area of residence. Although differences were observed among the departments, the numbers of emergency dialysis inpatients and maintenance dialysis inpatients increased. The number of surgeries also increased overall, particularly for maintenance dialysis patients (p = 0.0273). The percentage of DPC III patients was significantly higher in period B (p = 0.0368). CONCLUSIONS: The number of surgeries performed on maintenance dialysis patients and the overall DPC III rate significantly increased after the start of the COVID-19 pandemic at our hospital, suggesting that COVID-19 worsened the condition of maintenance dialysis patients and prolonged hospital stays.

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

Integrating Fréchet distance and AI reveals the evolutionary trajectory and origin of SARS-CoV-2.

A genome, composed of a precisely ordered sequence of four nucleotides (ATCG), encompasses a multitude of specific genome features like AAA motif. Mutations occurring within a genome disrupt the sequential order and composition of these features, thereby influencing the evolutionary trajectories and yielding variants. The evolutionary relatedness between a variant and its ancestor can be estimated by assessing evolutionary distances across a spectrum of genome features. This study develops a novel, alignment-free algorithm that considers both the sequential order and composition of genome features, enabling computation of the Fréchet distance (Fr) across multiple genome features to quantify the evolutionary status of a variant. Integrating this algorithm with an artificial recurrent neural network (RNN) reveals the quantitative evolutionary trajectory and origin of SARS-CoV-2, a puzzle unsolved by alignment-based phylogenetics. The RNN generates the evolutionary trajectory from Fr data at two levels: genome sequence mutations and organism variants. At the genome sequence level, SARS-CoV-2 evolutionarily shortens its genome to enhance its infectious capacity. Mutating signature features, such as TTA and GCT, increases its infectious potential and drives its evolution. At the organism level, variants mutating a single biomarker possess low infectious potential. However, mutating multiple markers dramatically increases their infectious capacity, propelling the COVID-19 pandemic. SARS-CoV-2 likely originates from mink coronavirus variants, with its origin trajectory traced as follows: mink, cat, tiger, mouse, hamster, dog, lion, gorilla, leopard, bat, and pangolin. Together, mutating multiple signature features and biomarkers delineates the evolutionary trajectory of mink-origin SARS-CoV-2, leading to the COVID-19 pandemic.

COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.

OBJECTIVES AND AIMS: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a disabling autoimmune disease of the central nervous system that requires immunosuppressants to control the relapses. The latter puts them at risk for more severe COVID-19 infection. Vaccines are an effective way to control the pandemic. However, we do not know how effective they are in immunologically compromised patients. We aimed to evaluate and compare antibody levels in NMOSD patients treated with disease-modifying therapies after two doses of inactivated and mRNA COVID-19 vaccines. METHODS: Patients with NMOSD diagnosis and age-sex matched healthy controls who received two doses of either inactivated and mRNA COVID-19 vaccine were recruited in the study. Serum samples were collected at least two weeks after the second dose. RESULTS: Serum samples from 24 NMOSD patients (Mean age-36.58, Female-70.83%) and 24 healthy controls (Mean age-36.71, Female-70.83%) were evaluated. Mean antibody titer was lower in the NMOSD group (Mean; SD (2.43 ± 1.51) than in healthy controls (Mean; SD 3.23 ± 0.80). Seronegativity was only seen in the rituximab group, there were no such cases in the azathioprine group. (9 vs 0). CONCLUSIONS: The study shows that NMOSD patients treated with rituximab may still be susceptible to severe COVID-19 infection even after both inactivated and mRNA vaccines.

Solidarity and reciprocity during the COVID-19 pandemic: a longitudinal qualitative interview study from Germany.

BACKGROUND: While solidarity practices were important in mitigating the Coronavirus Disease 2019 (COVID-19) pandemic, their limits became evident as the pandemic progressed. Taking a longitudinal approach, this study analyses German residents' changing perceptions of solidarity practices during the COVID-19 pandemic and examines potential reasons for these changes. METHODS: Adults living in Germany were interviewed in April 2020 (n = 46), October 2020 (n = 43) and October 2021 (n = 40) as part of the SolPan Research Commons, a large-scale, international, qualitative, longitudinal study uniquely situated in a major global public health crisis. Interviews were analysed using qualitative content analysis. RESULTS: While solidarity practices were prominently discussed and positively evaluated in April 2020, this initial enthusiasm waned in October 2020 and October 2021. Yet, participants still perceived solidarity as important for managing the pandemic and called for institutionalized forms of solidarity in October 2020 and October 2021. Reasons for these changing perceptions of solidarity included (i) increasing personal and societal costs to act in solidarity, (ii) COVID-19 policies hindering solidarity practices, and (iii) a perceived lack of reciprocity as participants felt that solidarity practices from the state were not matching their individual efforts. CONCLUSIONS: Maintaining solidarity contributes to maximizing public health during a pandemic. Institutionalized forms of solidarity to support those most in need contribute to perceived reciprocity among individuals, which might increase their motivation to act in solidarity. Thus, rather than calling for individual solidarity during times of crisis, authorities should consider implementing sustaining solidarity-based social support systems that go beyond immediate crisis management.

Comparison of inflammatory markers in COVID-19 patients- a study based on disease severity groups.

Objectives: To compare different inflammatory markers in various coronavirus disease 2019 severity groups. METHODS: The cross-sectional, retrospective, comparative study was conducted at the Central Park Teaching Hospital, Lahore, Pakistan, and comprised data from April to June 2021 of coronavirus disease 2019 inpatients. The data was divided into mild, moderate and severe/critical category using the World Health Organisation interim guidelines. Data was analysed using SPSS 22. RESULTS: Of the 50 patients, 29(58%) were males and 21(42%) were females. The overall mean age was 54.12±21.23 years. The mean age was 62±17.1years in critical group compared to 50±19.7 years in mild and 52±15.9 years in moderate groups. There were 8(16%) patients in the mild group, 16(32%) in the moderate group and 26(52%) in the critical severity group. Mortality was the outcome in overall 19(38%) cases, and 14(73.7%) of them were in the critical group (p=0.03). C reactive protein, interleukin-6, serum ferritin and D-dimer levels were significantly different among the groups (p<0.05). CONCLUSIONS: Older people were found to have experienced coronavirus disease 2019 in more severe forms. The inflammatory markers were significantly high in patients with severe disease and were associated with high mortality.

Superior neutralizing response after first versus second SARS-CoV-2 infection in fully vaccinated individuals.

Currently, the majority of the population has been vaccinated against COVID-19 and/or has experienced SARS-CoV-2 infection either before or after vaccination. The immunological response to repeated episodes of infections is not completely clear. We measured SARS-CoV-2 specific neutralization titers by a pseudovirus assay after BA.1 infection and RBD-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID-19 uninfected and triple vaccinated individuals (breakthrough infection group, BTI) as compared with those previously infected by SARS-CoV-2 (reinfection group, REI) who underwent identical vaccination schedule. SARS-CoV-2 specific neutralizing response after BA.1 infection was significantly higher in the BTI group as compared with the REI. Furthermore, neutralization titers in REI were not significant different from convalescent non reinfected controls. RBD-specific IgG and IgA, but not IgM, were also significantly higher in BTI as compared with REI. Our results show that the first episode of SARS-CoV-2 infection induces a significant increase in neutralizing titers in triple vaccinated individuals and that previous SARS-CoV-2 infection compromise significantly the neutralization response induced by reinfection, even by divergent SARS-CoV-2 variants and at least up to 2 years postinfection, suggesting a fundamental limitation in inducing effective booster through the intranasal route in previously infected individuals.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

Baseline gut microbiome features prior to SARS-CoV-2 infection are associated with host symptoms in and post COVID-19.

The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.

Estimating true prevalence through questionnaire data.

We present a general analytical method for obtaining unbiased prevalence estimates based on data from regional or national testing programs, where individual participation in the testing program is voluntary but where additional questionnaire data is collected regarding the individual-level reason/motivation for being tested. The approach is based on re-writing the conditional probabilities for being tested, being infected, and having symptoms, so that a series of equations can be defined that relate estimable quantities (from test data and questionnaire data) to the result of interest (an unbiased estimate of prevalence). The final estimates appear to be robust based on prima-facie examination of the temporal dynamics estimated, as well as agreement with an independent estimate of prevalence. Our approach demonstrates the potential strength of incorporating questionnaires when testing a population during an outbreak, and can be used to help obtain unbiased estimates of prevalence in similar settings.

A mathematical model of SARS-CoV-2 immunity predicts paxlovid rebound.

Nirmatrelvir/ritonavir (Paxlovid), an oral antiviral medication targeting SARS-CoV-2, remains an important treatment for COVID-19. Initial studies of nirmatrelvir/ritonavir were performed in SARS-CoV-2 unvaccinated patients without prior confirmed SARS-CoV-2 infection; however, most individuals have now either been vaccinated and/or have experienced SARS-CoV-2 infection. After nirmatrelvir/ritonavir became widely available, reports surfaced of "Paxlovid rebound," a phenomenon in which symptoms (and SARS-CoV-2 test positivity) would initially resolve, but after finishing treatment, symptoms and test positivity would return. We used a previously described parsimonious mathematical model of immunity to SARS-CoV-2 infection to model the effect of nirmatrelvir/ritonavir treatment in unvaccinated and vaccinated patients. Model simulations show that viral rebound after treatment occurs only in vaccinated patients, while unvaccinated (SARS-COV-2 naïve) patients treated with nirmatrelvir/ritonavir do not experience any rebound in viral load. This work suggests that an approach combining parsimonious models of the immune system could be used to gain important insights in the context of emerging pathogens.

pH-dependent endocytosis mechanisms for influenza A and SARS-coronavirus.

The ongoing SARS-CoV-2 pandemic and the influenza epidemics have revived the interest in understanding how these highly contagious enveloped viruses respond to alterations in the physicochemical properties of their microenvironment. By understanding the mechanisms and conditions by which viruses exploit the pH environment of the host cell during endocytosis, we can gain a better understanding of how they respond to pH-regulated anti-viral therapies but also pH-induced changes in extracellular environments. This review provides a detailed explanation of the pH-dependent viral structural changes preceding and initiating viral disassembly during endocytosis for influenza A (IAV) and SARS coronaviruses. Drawing upon extensive literature from the last few decades and latest research, I analyze and compare the circumstances in which IAV and SARS-coronavirus can undertake endocytotic pathways that are pH-dependent. While there are similarities in the pH-regulated patterns leading to fusion, the mechanisms and pH activation differ. In terms of fusion activity, the measured activation pH values for IAV, across all subtypes and species, vary between approximately 5.0 to 6.0, while SARS-coronavirus necessitates a lower pH of 6.0 or less. The main difference between the pH-dependent endocytic pathways is that the SARS-coronavirus, unlike IAV, require the presence of specific pH-sensitive enzymes (cathepsin L) during endosomal transport. Conversely, the conformational changes in the IAV virus under acidic conditions in endosomes occur due to the specific envelope glycoprotein residues and envelope protein ion channels (viroporins) getting protonated by H+ ions. Despite extensive research over several decades, comprehending the pH-triggered conformational alterations of viruses still poses a significant challenge. The precise mechanisms of protonation mechanisms of certain during endosomal transport for both viruses remain incompletely understood. In absence of evidence, further research is needed.

New-onset diabetes in COVID-19: The molecular pathogenesis.

Diabetes mellitus (DM) is still a challenging metabolic disease worldwide. In the current situation, the world is facing a COVID-19 pandemic due to SARS-CoV-2 infection. DM is one of the comorbid conditions that can worsen the severity of the COVID-19 condition. Surprisingly, SARS-CoV-2 infection can induce new-onset diabetes, a condition in which acute hyperglycemia occurs and may develop into a complication in nondiabetic patients. Angiotensinconverting enzyme 2 (ACE2) is a crucial entry factor for SARS-CoV-2 infection. ACE2 will bind to the spike protein of SARS-CoV-2, potentially initiating a damaging process in many tissues in the human body, including metabolic tissues. This mechanism suggests a potential role of ACE2 in the pathogenesis of diabetes since ACE2 has been proven to localize in essential metabolic tissues, one of which is the acini and islets part of the pancreas. This interrelated ACE2 in COVID-19 and DM is thought of as the mechanism that induces new-onset diabetes in COVID-19 patients. This review will thoroughly describe the current findings and theories regarding the molecular mechanism of SARS-CoV-2-induced new-onset diabetes and the possible therapeutic intervention.

Risks associated with acute pancreatitis (AP) with diabetic ketoacidosis (DKA) in COVID-19 patients: a literature review.

Background: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has become a global pandemic, and medical experts are scrambling to understand the wide range of symptoms and consequences of the virus. Although acute pancreatitis (AP) and pancreatic damage have been associated with SARS-CoV-2, the mechanism behind this is still unclear. The current article explores whether COVID-19 is an additional cause of AP and diabetic ketoacidosis (DKA). The article illustrates the conditions associated with AP and DKA among COVID-19 patients and diabetes mellitus (DM). Another critical condition is acute kidney injury (AKI), often associated with DKA. Methods: A search strategy for the article was assigned and retrieved from PubMed, Web of Science, and Scopus databases from 2020 to June 2022. The articles which discussed case studies on AP, DKA, and AKI were included in the study. Results: The present review of 24 reported case studies represented conditions of AP (12), DKA (5), AP and DKA (5), AP and AKI (1), and DKA and AKI (1) among COVID-19 participants, and showed a potential relationship between the complications. Conclusion: Healthcare during the COVID-19 pandemic plays a major role among AP, DKA, and AKI-associated COVID-19 patients. A compilation of case studies suggests effective management of COVID-19 infection-related complications such as AP, DKA, and AKI.

Histone mRNA polyadenylation-mediated inflammation underlies various virus infections and cancers.

The mechanistic understanding of virus infection and inflammation in many diseases is incomplete. Normally, messenger RNA (mRNA) tails of replication-dependent histones (RDH) that safeguard naked nuclear DNAs are protected by a specialized stem-loop instead of polyadenylation. Here, we showed that infection by various RNA viruses (including severe acute respiratory syndrome coronavirus 2) induced aberrant polyadenylation of RDH mRNAs (pARDH) that resulted in inflammation or cellular senescence, based on which we constructed a pARDH inflammation score (pARIS). We further investigated pARIS elevation in various disease conditions, including different types of virus infection, cancer, and cellular senescence. Notably, we found that pARIS was positively correlated with coronavirus disease 2019 severity in specific immune cell types. We also detected a subset of HIV-1 elite controllers characterized by pARDH "flipping" potentially mediated by HuR. Importantly, pARIS was positively associated with transcription of endogenous retrovirus but negatively associated with most immune cell infiltration in tumors of various cancer types. Finally, we identified and experimentally verified two pARIS regulators, ADAR1 and ZKSCAN1, which was first linked to inflammation. The ZKSCAN1 was known as a transcription factor but instead was shown to regulate pARIS as a novel RNA binding protein. Both regulators were upregulated under most infection and inflammation conditions. In conclusion, we unraveled a potential antiviral mechanism underlying various types of virus infections and cancers.

Statins in hospitalized COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with statins, compared with placebo or standard of care, were reviewed. Seven RCTs (enrolling 1830 participants) met the inclusion criteria. There was no statistically significant difference in all-cause mortality (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.75-1.13), length of hospital stay (weighted mean difference: -0.21 days, 95% CI: -1.01 to 0.59 days), intensive care unit (ICU) admission (RR: 1.84, 95% CI: 0.45-7.55), and mechanical ventilation (RR: 1.09, 95% CI: 0.70-1.70) between the two groups. Statins failed to reduce mortality, ICU admission, mechanical ventilation, and length of stay in hospitalized patients with COVID-19. Statins probably should not be used routinely in COVID-19 patients.

Immunisation against COVID-19 in Pregnancy and of Women Planning Pregnancy.

Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, although this is most likely an underestimate. Until vaccines became available, mortality and severe morbidity were costly in terms of life lost as well as the cost of supporting the severely and acutely ill. Vaccination changed the landscape, and following worldwide adoption, life has gradually been returning to normal. The speed of production of the vaccines was unprecedented and undoubtedly ushered in a new era in the science of fighting infections. The developed vaccines were on the already known platforms for vaccine delivery: inactivated virus, virus vector, virus-like particles (VLP) subunit, DNA and mRNA. The mRNA platform was used for the first time to deliver vaccines to humans. An understanding of these platforms and the pros and cons of each are important for clinicians who are often challenged by the recipients on the advantages and risks of these vaccines. These vaccines have so far and reassuringly been shown to be safe in reproduction (with no effect on gametes) and pregnancy (not associated with congenital malformations). However, safety remains paramount and continuing vigilance is critical, especially against rare fatal complications such as vaccine-induced thrombocytopenia and myocarditis. Finally, the waning immunity months after vaccination means repeated immunisation is likely to be ongoing, but just how often and how many such revaccinations should be recommended remains uncertain. Research into other vaccines and alternate delivery methods should continue as this infection is likely to be around for a long time.