Older Age and Vaccination Protect Against Transaminase Elevation in Pediatric SARS-CoV2 (preprint)

Objectives: SARS-CoV2 infection is reported to induce transaminase elevations. There are case reports of severe liver injury in adult SARS-CoV2 patients, and some have theorized that acute SARS-CoV2 infection may be a driver of severe liver injury in children. While pediatric hepatic injury has previously been described, clear shifts in immunogenic response secondary to prior immune exposure and vaccination since initial reports from 2020 warrant further evaluation. We sought to identify the impact of variant shifts and vaccination on this phenomenon in children. Methods: a retrospective cross sectional study of pediatric SARS-CoV2 patients seen at two hospital facilities in an urban neighborhood in New York City between March 2020 and March 2022 was conducted via chart review. Data was extracted relating to patients demographics, clinical presentation, including the level of care and the laboratory results of comprehensive metabolic panels (CMP). Results: 133 pediatric cases were identified as having SARS-CoV2 and CMP obtained in the same visit. Patients were predominantly Black (79.2%) and non-hispanic (87%) with a mean age of 9.2 years. Risk of transaminase elevation was increased in younger patients and patients with higher level of care. BMI was not a risk factor noted for transaminase elevation. Vaccination decreased degree, not incidence, of transaminase elevation but given low rates of vaccination unable to determine significance of protective efficacy. Conclusions: our study has identified a profound increased risk of transaminase elevation in younger patients, the absence of BMI as a correlating factor in our primarily black patient population, a shift towards non-specific AST elevation with variant windows, and a strong signal of vaccine protection.

Impact of COVID-19 pandemic on incident diagnosis patterns in German refugee centres: quasi-experimental study, 2018-2023 (preprint)

The COVID-19 pandemic may have affected morbidity patterns of residents in refugee centres, but empirical evidence is scarce. We utilised linked data from a health surveillance network in German refugee centres, employing a quasi-experimental design to examine the effects of the COVID-19 pandemic on newly diagnosed medical conditions. These diagnoses were coded in on-site healthcare facilities for refugee patients. Our analysis encompasses the timeframe from October 2018 to April 2023 and includes individual-level data for 109,175 refugees. This data resulted in 76,289 patient-months across 21 refugee centres, with a total occupancy of 144,012 person-months. We employed segmented regression analyses, adjusting for time trends, socio-demographic factors, centre occupancy, and centre-specific characteristics, to evaluate the COVID-19 pandemic's impact on incident diagnosis patterns among refugees. The COVID-19 pandemic significantly altered diagnosis patterns among refugees in German centres. Notably, incidents of injuries, mental disorders, psychotherapeutic drug prescriptions, and genitourinary diseases rose, while respiratory diseases decreased, later rebounding. An 88% increase in injury-related diagnoses suggests heightened violence experiences during flight or in centres. Mental disorder diagnoses and psychotherapeutic drug prescriptions rose by 73% and 95%, reflecting pandemic-related stressors in refugee centres, highlighting the pandemic's multifaceted impact on refugee health.

Prevalence of hepatitis A virus among migrant workers in Qatar: A national study (preprint)

Background: Hepatitis A virus (HAV) is the predominant cause of acute viral hepatitis worldwide; however, data on HAV antibody prevalence (seroprevalence) among migrant populations are limited. This study aimed to investigate HAV seroprevalence among Qatar's migrant craft and manual workers (CMWs), constituting approximately 60% of the country's population. Methods HAV antibody testing was conducted on stored serum specimens obtained from CMWs during a nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population-based cross-sectional survey between July 26 and September 9, 2020. Associations with HAV infection were investigated through regression analyses. Results Of the 2,607 specimens with HAV antibody test results, 2,393 were positive, and 214 were negative. The estimated HAV seroprevalence among CMWs was 92.0% (95% CI: 90.9-93.1%). HAV seroprevalence was generally high but exhibited some variation, ranging from 70.9% (95% CI: 62.4-78.2%) among Sri Lankans to 99.8% (95% CI: 98.2-99.9%) among Pakistanis. The multivariable regression analysis identified age, nationality, and educational attainment as statistically significant factors associated with HAV infection. Relative to CMWs aged ≤29 years, the adjusted relative risk (ARR) was 1.06 (95% CI: 1.03-1.10) in CMWs aged 30-39 years and reached 1.15 (95% CI: 1.10-1.19) in those aged ≥50 years. In comparison to Indians, the ARR was lower among Sri Lankans, assessed at 0.81 (95% CI: 0.72-0.91), but higher among Nepalese at 1.07 (95% CI: 1.04-1.11), Bangladeshis at 1.10 (95% CI: 1.07-1.13), Pakistanis at 1.12 (95% CI: 1.09-1.15), and Egyptians at 1.15 (95% CI: 1.08-1.23). No evidence for differences was found by geographic location or occupation. Conclusions HAV seroprevalence among Qatar's CMW population is very high, with over nine out of every ten individuals having been exposed to this infection, likely during childhood.

Hydroxychloroquine safety, comparison between no Covid-19 and Covid-19 patients. Data from the Spanish Pharmacovigilance Database (preprint)

Aim: To compare the cases reported to the Spanish Pharmacovigilance System (SEFV-H) with HCQ used in COVID-19 vs. HCQ used in other indications. Methods. All cases of adverse drug reactions (ADR) submitted to the Spanish Pharmacovigilance database (FEDRA) from 1 January 1982 to 19 February 2021 suspected to be induced by HCQ were identified. Cases were classified into two groups: no-Covid patients and Covid patients. Frequencies of ADR were compared. Reporting Odds Ratios (ROR) with its lower limit of the 95% confidence interval (-ROR) and Omega (Ω) and its lower limit of the 95% credibility interval (Ω -025) were obtained to estimate disproportionalities. Results. More severe cases were reported with the use of HCQ in Covid. Main differences in frequency were observed in hepatobiliary, skin, gastrointestinal, eye, nervous system and heart ADRs. During the Covid-19 pandemic, disproportionality was found for Torsade de Pointes/QT prolongation with a ROR (-ROR) of 132.8 (76.7); severe hepatotoxicity, 18.7 (14.7); dyslipidaemias, 12.1 (6.1); shock, 9.5 (6.9) and ischaemic colitis, 8.9 (2.6). Myopathies, haemolytic disorders and suicidal behaviour increased their disproportionality during the pandemic. Disproportionality was observed for neoplasms, haematopoietic cytopaenias and interstitial lung disease in the pre-Covid period. Ω showed potential interactions between HCQ and azithromycin, ceftriaxone, lopinavir and tocilizumab . Conclusions. The use of HCQ in Covid-19 changed its safety profile. Of particular concern during the pandemic were arrhythmias, hepatotoxicity, severe skin reactions and suicide risk, but not ocular disorders. Some ADRs identified as signals would require more detailed analyses.

The completion rates of radiotherapy or chemoradiotherapy did not change after SARS-CoV-2 Omicron infection (preprint)

Background: The SARS-CoV-2 Omicron pandemic had a global impact on individuals with cancers. This study aimed to investigate the effect of Omicron infection on cancer patients in China. Methods: A retrospective study was conducted, including 347 patients with cancer who received radiotherapy or chemoradiotherapy between July 2022 and March 2023. The patients were divided into three groups: those without SARS-CoV-2 infection during treatment (Non-COVID-19 group), those who began treatment at least 10 days after first testing positive for SARS-CoV-2 (≥10-d COVID-19 group), and those who began treatment less than 10 days after first testing positive for SARS-CoV-2 (<10-d COVID-19 group). The serum levels of SAA, hsCRP, ALT, etc, were used to assess the severity of inflammation, liver damage, and cardiovascular injury. Results: The proportion of moderate and severe infected cases was higher in ≥10-d COVID-19 group compared with <10-d COVID-19 group (p=0.0446). Additionally, the serum levels of SAA, hsCRP, IL-6 and PCT, were significantly higher in ≥10-d COVID-19 group (p<0.05). Serum ALT, LDH and HBDH levels were also elevated in ≥10-d COVID-19 group (p<0.05). However, no significant differences were observed in frequency of neutropenia, thrombocytopenia and completion rates among three groups. Conclusion: Omicron infection leads to inflammation, liver damage and cardiovascular injury in cancer patients. Surprisingly, the duration of delay in radiotherapy or chemoradiotherapy after Omicron infection did not affect completion rates of current therapy, which was not consistent with the recommendations of NCCN guidelines. Moreover, the severity of Omicron infection was worse among cancer patients who received delayed treatment.

Antigen non-specific CD8+ T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection (preprint)

Primarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed "long COVID". Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8+ T cells within the brains of aged animals but reduced antigen specificity of those CD8+ T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8+ T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8+ T cell-derived IFN-{gamma} correlated with neuronal death. These results support the evidence that CD8+ T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals. eTOC summaryUsing a murine model of respiratory coronavirus infection, we show that aging amplifies post-infectious cognitive dysfunction due to activated CD8+ T cells that secrete IFN-{gamma} in the brain. These data provide evidence that CD8+ T cells in the brain negatively impact post-infectious cognitive function.

Do we need a ban on firecrackers? Explosion injuries to hands caused by pyrotechnic objects during the turn of the year in Berlin/Brandenburg (preprint)

Introduction: Fireworks carry a high risk for hand injuries. Methods: The study presents data of 146 patients hospitalized with hand injuries caused by fireworks during the turn of the years 2005 to 2023. Statistical data presented include number, age and sex, injury patterns and concomitant injuries. Results: The number of injured increased over the years with a significant increase in 2016 and incision during the COVID pandemic. Those affected were predominantly male. The age group between 19 and 36 years was the most represented, followed by elders between 37 and 65 years. Children and adolescents under 18 were affected in one-third of cases. Injury patterns included combinations of soft tissue lesions, open fractures and finger amputations. Concomitant injuries predominantly involved the head. One quarter of the patients showed post-traumatic stress disorder. Discussion: Hand injuries from fireworks often result in permanent physical integrity disorders. Posttraumatic stress disorder is often. The increasing number of cases may be due to structural changes in the rescue service and the level of awareness of a specialized facility, in addition to a fundamental increase in injuries. Most striking was the decline in numbers during the COVID pandemic. The immediate rebound after the end of the restrictions supports the consideration of a permanent ban.

Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age (preprint)

ObjectiveBeginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DesignWe conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. ResultsCompared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. ConclusionThese results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare ([~]1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. What is already known on this topicClusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent. What this study addsSARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. How this study might affect research, practice or policyDespite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.

Patterns in Domestic Injuries and how COVID-19 Lockdown Measures Changed Their Incidence in Mexico (preprint)

Domestic accidents occur worldwide. From small burns and bruises to significant wounds and injuries from dangerous falls, not all of them reach clinical care; so to measure the toll of these hardships on society, we surveyed three major cities in Mexico to better understand the problem and how coronavirus disease 2019 (COVID-19) lockdown measures changed the incidence rate. We conducted an analytical cross-sectional study using Microsoft Forms, with a digital survey distributed among the Mexican population from October 2021 to November 2021, during lockdown. The incidence of all injuries surveyed increasedduring the first year of the COVID-19 pandemic. A comparison of the time spent inside the house before and during the pandemic showed that only burns increased. The number of wounds and musculoskeletal injuries decreased as people spent more time at home. Women were shown to be the most vulnerable group. This study offers an unprecedented perspective on home-related trauma, as past literature has mainly examined trauma injuries treated in hospitals. The types of wounds have morphed depending on the percentage of time spent in the house, which has undergone a remarkable transformation since the lockdown was enacted.

Primary Liver Rhabdomyosarcoma in a Burnt-out disease: An unusual presentation (preprint)

Rhabdomyosarcoma is the most common soft tissue sarcoma in children. However, Primary hepatic RMS is rare and less than 20 cases are reported in literature. We present the case of a neonate who presented to us with a lumbar mass and lost follow-up during COVID pandemic. She came back to us with a Primary liver Rhabdomyosarcoma in the setting of a burnt out disease. In the setting of a diagnostic dilemma, we found histopathology as the cornerstone to diagnosis. Multimodality therapy based on the experience of similar case reports is the answer is such rare cases where specific guidelines are not yet defined.

Effect Of Molnupiravir On Ichemia/Reperfusion Damage In Rat Liver, An Experimental Study (preprint)

Background Ischemia occurs when blood supply to tissues is limited, resulting in cellular dysfunction and necrosis. Reperfusion, or the process of restoring blood flow, can result in an overabundance of reactive oxygen species (ROS) and toxic byproducts. The I/R (Ischemia / Reperfusion) technique used in liver resection and transplantation has been linked to liver damage. Molnupiravir, a non-hepatotoxic oral medicine, is converted into N-hydroxycytidine (NHC). The purpose of this study is to see how molnupiravir affects I/R-induced damage of liver in rats.Methods We divided the rats into three groups: Sham operation (SG) (n = 6), Liver I/R (LIR) (n = 6), and Molnupiravir + Liver I/R (MIR) (n = 6) groups. The MIR group (n = 6) received 40 mg/kg of molnupiravir. All animals were subjected to laparotomy, hepatic ischemia (1 hour), and reperfusion (6 hours). At the end of the trial, liver tissue samples were tested for IL-1β, tGSH, NF-κB, MDA, and TNF-α levels, as well as histopathological examination. The levels of ALT and AST in the blood were determined. The MIR group's results were in comparison to the SG and LIR groups.Results Biochemical examination revealed that NF-ƘB, MDA, TNF-α, IL-1β, ALT, and AST measurements were higher in the LIR and MIR groups than in the SG group. The SG group had the highest tGSH values. Histopathological examinations revealed that the MIR group had the most damage.Conclusion While molnupiravir, which is included in COVID-19 treatment regimen since it has no projected liver toxicity, does not affect healthy liver tissue, it does exacerbate ischemia/reperfusion injury in stressed liver tissue. Molnupiravir should be used with caution because it has the potential to aggravate liver damage during procedures such as liver transplantation or resection.

A clustering and graph deep learning-based framework for COVID-19 drug repurposing (preprint)

Drug repurposing (or repositioning) is the process of finding new therapeutic uses for drugs already approved by drug regulatory authorities (e.g., the Food and Drug Administration (FDA) and Therapeutic Goods Administration (TGA)) for other diseases. This involves analyzing the interactions between different biological entities, such as drug targets (genes/proteins and biological pathways) and drug properties, to discover novel drug-target or drug-disease relations. Artificial intelligence methods such as machine learning and deep learning have successfully analyzed complex heterogeneous data in the biomedical domain and have also been used for drug repurposing. This study presents a novel unsupervised machine learning framework that utilizes a graph-based autoencoder for multi-feature type clustering on heterogeneous drug data. The dataset consists of 438 drugs, of which 224 are under clinical trials for COVID-19 (category A). The rest are systematically filtered to ensure the safety and efficacy of the treatment (category B). The framework solely relies on reported drug data, including its pharmacological properties, chemical/physical properties, interaction with the host, and efficacy in different publicly available COVID-19 assays. Our machine-learning framework reveals three clusters of interest and provides recommendations featuring the top 15 drugs for COVID-19 drug repurposing, which were shortlisted based on the predicted clusters that were dominated by category A drugs. The anti-COVID efficacy of the drugs should be verified by experimental studies. Our framework can be extended to support other datasets and drug repurposing studies, given open-source code and data availability.

The impact of the COVID-19 pandemic on treatment for domestic violence injuries: evidence from medical claims (preprint)

Previous studies have observed heterogeneous changes in domestic violence-related 911 calls, police incident reports, and arrests at the onset of the COVID-19 pandemic. In this study, we use a large-scale medical claims database with coverage of over 100 million patients to examine the impact on domestic violence victims’ use of emergency department care for their injuries in the early weeks of the pandemic compared to the corresponding weeks in previous years. We find a 35% decrease in utilization of emergency medical services by domestic violence victims between March and June of 2020. Based on this finding, it is essential to use caution when using medical claims to measure domestic violence in future research covering this time period. Decreases in care utilization also have important implications for the detection, screening, and treatment of domestic violence injuries during future public health crises.

Ivermectin drug induced liver injury.

Ivermectin remains a popular, albeit unproven, therapy used in both the prevention and treatment of COVID-19. We discuss a patient who developed jaundice and a liver injury 3 weeks after initiating ivermectin for COVID prevention.  Liver histology demonstrated a pattern of injury that was both portal and lobular, with a bile ductulitis as well with marked cholesasis. She was managed with low dose corticosteroids, later tapered and withdrawn. She remains well a year after presenting.

Early treatment with N-acetylcysteine reduces hepatotoxicity in acute acetaminophen poisoning.

During the outbreak of COVID19 measures taken to contain the spread of the virus have influenced the mental well-being of adults and adolescents. Acetaminophen overdose is the major cause of drug intoxication among children and adolescents. We reported a case of a 15-year- old girl referred to our Emergency Department 3 hours after ingestion of 10 g of paracetamol for suicidal purposes. She promptly started the administration of intravenous N-acetylcysteine (NAC) and the patient was discharged after 5 days of hospitalization in good clinical condition and with neuropsychiatric follow-up. Our case shows that the timing of the intravenous NAC administration is considered the most important factor in the prevention of acetaminophen-induced hepatic failure, despite high serum levels after acetaminophen ingestion.

[Treatment of toxic hepatitis in COVID-19 patients].

BACKGROUND: The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. AIM: The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. MATERIALS AND METHODS: On the basis of the newly created infection centers of the Central Clinical Hospital "RZhD-Medicine" and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. RESULTS: On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower - 122 (55.2%) and 134 (58.8%); p<0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. CONCLUSION: The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

The Prophylactic Effect of Vitamin C and Vitamin B12 against Ultraviolet-C-Induced Hepatotoxicity in Male Rats.

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm2) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant-antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1ß, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Improving modelling for epidemic responses: reflections from members of the UK infectious disease modelling community on their experiences during the COVID-19 pandemic (preprint)

The COVID-19 pandemic both relied and placed significant burdens on the experts involved from research and public health sectors. The sustained high pressure of a pandemic on responders, such as healthcare workers, can lead to lasting psychological impacts including acute stress disorder, post-traumatic stress disorder, burnout, and moral injury, which can impact individual wellbeing and productivity. As members of the infectious disease modelling community, we convened a reflective workshop to understand the professional and personal impacts of response work on our community and to propose recommendations for future epidemic responses. The attendees represented a range of career stages, institutions, and disciplines. This piece was collectively produced by those present at the session based on our collective experiences. Key issues we identified at the workshop were lack of institutional support, insecure contracts, unequal credit and recognition, and mental health impacts. Our recommendations include rewarding impactful work, fostering academia-public health collaboration, decreasing dependence on key individuals by developing teams, increasing transparency in decision-making, and implementing sustainable work practices. Despite limitations in representation, this workshop provided valuable insights into the UK COVID-19 modelling experience and guidance for future public health crises. Recognising and addressing the issues highlighted here is crucial, in our view, for ensuring the effectiveness of epidemic response work in the future.

AMA-positive hepatitis induced by the SARS-CoV-2 vaccine.

We present the case of a 56-year-old female admitted to our centre for hepatitis. She had recieved the first dose of the BNT162b2 vaccine against SARS-CoV-2 10 days before the admission. Etiologic study was negative. The patient was diagnosed with vaccine-induced hepatitis.