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Background: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. Methods: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. Results: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9–48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. Conclusions: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.

Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and Methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58–0.85]; P = 4 ×10−4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.

The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.

Risk of cardiovascular events is increased after COVID-19. However, information on cardiovascular risk trends after COVID-19 infection is lacking and estimates by sex are inconsistent. Our aim was to examine cardiovascular outcomes and mortality in a large cohort (164,346 participants) of SARS-CoV-2 positive individuals compared to non-positive individuals, stratified by sex. Data were obtained from the Spanish Health System’s electronic medical records. Selected individuals were ≥ 45 years old with/without a positive SARS-CoV-2 test in the period March-May 2020. Follow-up was obtained until January 31, 2021, for cardiovascular events (angina/myocardial infarction, arrhythmias, bypass/revascularization, heart failure, peripheral artery disease, stroke/transient ischemic attack, and thrombosis), and until March 31, 2021, for mortality. Individuals were matched by propensity score. Incidence of cardiovascular events and mortality was compared with accelerated failure time models. The effect of matching and of COVID-19 severity was assessed with sensitivity analyses. In the first 3 months of follow-up, SARS-CoV-2 positive individuals had a higher risk of mortality and of all cardiovascular events. From 4–12 months, there was increased risk of mortality in SARS-CoV-2 positive individuals overall, of heart failure in SARS-CoV-2 positive females (HR= 1.26 [1.11–1.42]), and of arrhythmias and thrombosis in SARS-CoV-2 positive males (HR= 1.29 [1.14–1.47] and HR= 1.35 [1.03–1.77], respectively). When COVID-19 patients admitted to the ICU were excluded, incidence of thrombosis was similar in males regardless of positive/non-positive SARS-CoV-2 status. In the full year of follow-up, increased incidence of heart failure and of arrhythmias and thrombosis was observed in SARS-CoV-2 positive females and males, respectively.

Summary: Background and Aims: Passive transfer of antibodies through breastfeeding is a potential mode of protection for newborns and infants following maternal SARS-CoV-2 infection. The primary goal of this study was to evaluate and characterize SARS-CoV-2 Spike (S)-specific antibodies in human milk samples collected longitudinally from a cohort of convalescent mothers. Methods: SARS-CoV-2 infected participants enrolled in this study were lactating women aged 29–36 years with a confirmed COVID-19 diagnosis who donated milk samples at intervals over the six-month study period. Samples were evaluated for antibody subclass SARS-Cov-2 S glycoprotein binding activity by ELISA, and for the capacity of antibodies purified from these samples to mediate neutralizing antibody (nAb) activity in S pseudovirus inhibition assays and phagocytic activity in an antibody-dependent phagocytosis assay. Results: Robust S-reactive IgM, IgG and IgA ELISA titers were found at day 7 after enrollment, with IgG and IgA levels persisting through 6 months. The majority of S-reactive IgA in milk was secretory in nature. Strong IgG (mean IC50 value 29.19μg/ml) and IgA (mean IC50 value 10.17μg/ml) nAb activity was found in all convalescent samples at 14 days with a decline by 3 months after the onset of symptoms but was not seen in pre-pandemic controls. Both IgG and IgA antibodies mediated phagocytic activity in samples from all subjects by day 14 after the onset of symptoms. Conclusions: Our findings indicate that human milk from SARS-CoV-2 infected mothers have the capacity to transfer SARS-CoV-2-specific antibodies capable of mediating multiple functional activities to newborns via breastfeeding.

Background: Data on SARSCoV-2 infection in children with hematological malignancies (HM) are limited. Here, we describe the clinical features of children with HM after SARS-CoV-2 infection and investigate the potential risk factors for disease severity. Methods: Children with HM and SARS-CoV-2 infection from five hospitals in five cities in Henan, China from October 2022 to January 2023 were retrospectively included. Clinical information and Coronavirus disease 2019 (COVID-19) vaccination status were collected for further analyses. Results: A total of 285 children with HM and SARS-CoV-2 infections were included. COVID-19 was asymptomatic in 3.2% of the patients (n = 9), mild in 89.1% (n = 254), moderate in 5.3% (n = 15), severe in 1.8% (n = 5), and critical in 0.7% (n = 2). Fever (92.4%) and cough (56.9%) were the most common symptoms. Most (249, 88.3%) children were managed at home during their COVID-19 illness. Of the 36 children admitted to the hospital, two required intensive care unit care, 11 required supplementary oxygen, and two non-invasive ventilation. A total of 283 (99.3%) children fully recovered and two (0.7%) died due to COVID-19. Significant risk factors for increased severity of infection in multivariable analyses were the presence of comorbidity (OR, 10.4; 95%CI, 2.8–38.7; p

Coronavirus disease 2019 (COVID-19) is a viral pandemic and a matter of concern. It also mimics viral pneumonia with cough and fever but also causes severe sequels and various complications. Subdural empyema is a very rare brain infection presenting mostly with fever, weakness, and altered level of consciousness, and has been recently noted as a new complication of COVID-19. This report presents 3 cases of subdural empyema with a prior history of COVID-19. The first case is a 17-year-old female presented with a 1-week history of severe progressive headache, right-sided ptosis, and left-sided hemiplegia with a history of COVID-19 in about 40 days before admission. The second one is a 41-year-old female presented with a 2-week history of fatigue, severe progressive headache which deteriorated while sitting, left tarsal swelling, and left-sided hemiparesis accompanied by drowsiness since 1 day before admission and a history of COVID-19 in about 50 days before admission. The third one is a 47-year-old gentleman with a known case of epilepsy, who presented with a 2-day history of headache and fever and an event of Generalized Tonic Colonic (GTC) seizure on the day of admission. The patient had a history of multiple head traumas during past years, which led to craniectomy, and also a history of COVID-19 about 46 days before admission. Emergent surgery was performed to evacuate empyema, and patients underwent subsequent anti-bacterial treatment. All patients showed clinical improvement. This report highlights a potential link between SARS-COV-2 infection and the patient's development of subdural empyema.

Background: Little is known about the dermatologic manifestations of multisystem inflammatory syndrome in children (MIS-C) in children and adolescents. Objective: We sought to describe the demographic background, key clinical features, and the clinical consequences of developing rash manifestations in MIS-C patients at Texas Children’s Hospital. Methods: Descriptive retrospective cohort study of 290 hospitalized eligible patients between May 2020 and April 2022. Results: Among MIS-C patients, 51% exhibited a rash. We found that younger children (8.62 vs 9.49 years of age, P = .006) and White children (P = .002) had a higher likelihood of developing a rash in association with MIS-C. Additionally, patients without a rash had increased maximum troponin levels (0.11 ng/mL vs 0.07 ng/mL, P = .02) and a higher incidence of cardiac involvement (83.1% vs 72.3%, P = .03) compared to those with a rash but did not significantly affect the length of hospital stay or clinical course. The most commonly observed rash was an erythematous and maculopapular rash on the trunk and/or extremities. Limitations: Rash characteristics were initially described by a variety of physicians in the pediatric primary care services. Conclusion: Rash manifestations in MIS-C patients are associated with lower cardiac involvement and decreased troponin levels.

Introduction and aims: Pandemic lockdown measures are a cause of concern, regarding their negative impact on the mental health of individuals. The results of numerous studies have associated the appearance of gastrointestinal symptoms with different psychologic disorders, such as stress, depression, and anxiety, due to gut-brain axis interaction. The aim of the present study was to determine the prevalence of, and factors associated with, gastrointestinal symptom onset related to the COVID-19 pandemic lockdown and various lifestyle modifications. Methods: An analytic, observational, and cross-sectional study was conducted on an open population that agreed to participate within the time frame of January to May 2021. Results: A total of 298 subjects, 165 of whom were women (55.4%), agreed to participate and the mean patient age was 36.1 ± 12.6 years. There was a significant increase in the frequency of several gastrointestinal symptoms: epigastric burning, early satiety, heartburn, regurgitation, constipation, and diarrhea. Changes in weight and modifications in lifestyle were found to be associated variables. Conclusions: The results of this study showed a significant increase in a wide variety of gastrointestinal symptoms related to lifestyle changes due to the pandemic lockdown. Weight change, supplement and multivitamin intake, and reduced physical activity were the main associated risk factors. Public healthcare systems should take a multidisciplinary approach into consideration for the care of affected individuals. Resumen: Antecedentes: Las medidas de confinamiento pandémico han generado preocupaciones sobre su impacto en la salud mental de las personas. La aparición de síntomas gastrointestinales ha sido asociada en múltiples estudios con diversos trastornos psicológicos como el estrés, la depresión y la ansiedad, debido a la interacción del eje intestino-cerebro. Este estudio tuvo como objetivo determinar la prevalencia y los factores asociados con el inicio de síntomas gastrointestinales relacionados con el confinamiento por la pandemia de COVID-19 y varias modificaciones en el estilo de vida. Métodos: Se realizó un estudio observacional, transversal y analítico en una población abierta que aceptó participar entre enero y mayo de 2021. Resultados: Doscientos noventa y ocho sujetos aceptaron participar, 165 mujeres (55,4%); la edad promedio fue de 36.1 ± 12.6 años, se observó un aumento significativo en la frecuencia de varios síntomas gastrointestinales: ardor epigástrico, saciedad temprana, acidez, regurgitación, estreñimiento y diarrea. Los cambios en el peso y las modificaciones en el estilo de vida se encontraron como variables asociadas. Conclusiones: En este estudio, se encontró un aumento significativo en una amplia variedad de síntomas gastrointestinales relacionados con modificaciones en el estilo de vida debido al confinamiento. Los cambios en el peso, la ingesta de suplementos y multivitaminas, y la disminución de la actividad física fueron los principales factores de riesgo asociados. Los sistemas de salud pública deben tener en cuenta un enfoque multidisciplinario para el cuidado de estas personas.

Detecting anti-PF4 antibodies remains the golden diagnostic method for heparin-induced thrombocytopenia (HIT) diagnosis with high sensitivity and specificity. Various lab tests detect anti-PF4 antibodies, including immunoassays and functional assays. Even with positive detection of the anti-PF4 antibody, several factors are involved in the result. The concept of anti-PF4 disorders was recently brought to light during the COVID pandemic since the development of vaccine-induced thrombotic thrombocytopenia (VITT) with the adenovirus-vectored-DNA vaccine during the pandemic. Circumstances that detect anti-PF4 antibodies are classified as anti-PF4 disorders, including VITT, autoimmune HIT and spontaneous HIT. Some studies showed a higher percentage of anti-PF4 antibody detection among the population infected by COVID-19 without heparin exposure and some supported the theory that the anti-PF4 antibodies were related to the disease severity. In this review article, we provide a brief review of anti-PF4 disorders and summarize the current studies of anti-PF4 antibodies and COVID-19 infection.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), turned into a global pandemic, and there remains an urgent demand for specific/targeted drugs for the disease. The 3C-like protease (3CLpro) is a promising target for developing anti-coronavirus drugs. Schisandra sphenanthera fruit is a well-known traditional Chinese medicine (TCM) with good antiviral activity. This study found that the ethanolic extract displayed a significant inhibitory effect against SARS-CoV-2 3CLpro. Forty-four compounds were identified in this extract using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Combining molecular docking and in vitro experiments, we found that two epimeric 7,8-secolignans, rel-(1S,2R)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate (2) and rel-(1S,2S)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate (4), potently inhibited 3CLpro with IC50 values of 4.88 ± 0.60 μM and 4.75 ± 0.34 μM, respectively. Moreover, in vivo and in vitro experiments indicated that compounds 2 and 4 were potent in regulating the inflammatory response and preventing lung injury. Our findings indicate that compounds 2 and 4 may emerge as promising SARS-CoV-2 inhibitors via 3CLpro inhibition and anti-inflammatory mechanisms.

Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase, is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity, leading to degradation of IFT46, a protein component of the intraflagellar transport (IFT) complex B. This results in dysfunctional cilia, which explains certain symptoms that are specific to COVID-19. However, the precise molecular mechanism of how ORF10 recognizes CUL2ZYG11B remains unknown. Here, we determined the crystal structure of CUL2ZYG11B complexed with the N-terminal extension (NTE) of SARS-CoV-2 ORF10 (2.9 Å). The structure reveals that the ORF10 N-terminal heptapeptide (NTH) mimics the Gly/N-degron to bind CUL2ZYG11B. Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2ZYG11B both in ITC assay and in vivo cells. In addition, we prove that enhancement of CUL2ZYG11B activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2ZYG11B. Finally, we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif, thereby binding competitively to CUL2ZYG11B and inhibiting the degradation of target substrates bearing the Gly/N-degron motif. Overall, this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation, and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2ZYG11B interaction, while pinpointing a promising target for the development of treatments for COVID-19.

There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, and toxicity have been reported in previous studies. Thus there is a dearth of new treatment options for SARS-CoV-2. In this work, a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 activity. One compound, designated 172, demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of concern. Mechanistic studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease (3CLpro) by binding to an allosteric site and reduces 3CLpro dimerization. A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in vitro. In vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 mice. Overall, this study identified an alternative druggable site on the SARS-CoV-2 3CLpro, proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

Background/Objective: Multiple cases of postvaccination immune-related adverse events have been reported. We, hereby, present a patient who presented with new-onset type 1 diabetes mellitus (DM) after COVID-19 messenger RNA (mRNA) vaccination. Case Report: A 38-year-old Caucasian man presented with sudden onset of polyuria, polydipsia, and blurry vision for 1 month. The patient received the second dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech) 4 weeks prior to symptom onset. Initial workup revealed glucosuria and hemoglobin A1c of 9.4%. Antibodies against multiple pancreatic beta cell autoantigens were detected. The patient was then initiated on insulin. Discussion: Hypothesized mechanisms for development of type 1 DM after COVID-19 mRNA vaccination include molecular mimicry, autoimmune/inflammatory syndrome induced by adjuvants, and possible interaction between the angiotensin-I converting enzyme-2 receptor on beta cells and viral mRNA. An initial high index of suspicion should be accompanied by early autoantibody testing and initiation of insulin, if indicated. Finally, if diagnosed with type 1 diabetes, patients must have long-term follow-up as there may be brief periods where glycemic control is maintained off insulin. Conclusion: New-onset type 1 DM has been reported after COVID mRNA vaccination. Clinicians should maintain a high index of suspicion and pursue early testing for the same to reduce adverse outcomes and improve long-term prognosis.

Wastewater surveillance (WWS) can leverage its wide coverage, population-based sampling, and high monitoring frequency to capture citywide pandemic trends independent of clinical surveillance. Here we conducted a nine months daily WWS for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 12 wastewater treatment plants (WWTPs), covering approximately 80% of the population, to monitor infection dynamics in Hong Kong, China. We found that the SARS-CoV-2 virus concentration in wastewater was correlated with the daily number of reported cases and reached two pandemic peaks three days earlier during the study period. In addition, two different methods were established to estimate the prevalence/incidence rates from wastewater measurements. The estimated results from wastewater were consistent with findings from two independent citywide clinical surveillance programmes (rapid antigen test (RAT) surveillance and serology surveillance), but higher than the cases number reported by the Centre for Health Protection (CHP) of Hong Kong, China. Moreover, the effective reproductive number (Rt) was estimated from wastewater measurements to reflect both citywide and regional transmission dynamics. Our findings demonstrate that large-scale intensive WWS from WWTPs provides cost-effective and timely public health information, especially when the clinical surveillance is inadequate and costly. This approach also provides insights into pandemic dynamics at higher spatiotemporal resolutions, facilitating the formulation of effective control policies and targeted resource allocation.

Background: COVID-19 has further burdened the Brazilian healthcare system, especially emergencies. Patients may have delayed seeking care for surgical abdominal pain. Delays in the approach may have impacted clinical evolution and outcomes. This study evaluated appendectomies and their complications performed by the public system during one-year follow-up of COVID-19 in a hospital in southern Brazil. Materials and methods: In this hospital-based cross-sectional study, we included adult patients who underwent appendectomy from March 2019 to April 2021 (n = 162). Patients were divided into pre-pandemic (n = 78) and pandemic (n = 84) groups based on the surgery date. The analyzed variables included hospitalization duration, intensive care unit (ICU) admission, surgical approach, histopathological findings, COVID-19 testing, patient outcomes, and 30-day survival rate. Results: The cohorts exhibited similar epidemiology, with the sex ratio and average age being maintained. No statistical difference was found in the 30-day survival rate and clinical outcomes. Of the four patients admitted to the ICU, three belonged to the pandemic cohort and tested negative for COVID-19. Only 47.6 % of the patients in the pandemic cohort underwent COVID-19 polymerase chain reaction examination; one tested positive (2.5 %). Conclusion: This study demonstrated that there was no increased risk for appendectomies during the first wave of the pandemic. Surgeries were safe during this period. Patients continued to access the emergency service despite surgical abdominal pain and restrictive measures imposed by health authorities. The similar results observed across cohorts are attributed to the readiness of the teams and the availability of medical surgical equipment in safe quantities.

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016–2019) and exposed (2020−2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P

Summary: Background: Liver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood. Methods: Immunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19. The 10x Genomics Visium CytAssist Spatial Gene Assay was designed to analyze liver transcriptomics. TCR CDR3 sequences were analyzed in DNA from liver tissues. Liver function indicators were retrospectively studied in 650 hospitalized patients with COVID-19. Findings: SARS-CoV-2 proteins were initially detected in the livers of naturally infected golden (Syrian) hamsters, prompting us to investigate the situation in clinical cases. Thus, we collected liver tissues from patients with abnormal liver biochemical values. Viral S and N proteins were detected in the livers of severe and deceased patients but not in those of moderate patients. We further demonstrated that hepatocytes and erythroid cells in hepatic sinusoids are major cells targeted by SARS-CoV-2. Immune cells, especially T cells, were enriched in surviving severe patients, characterized by enhanced CDR3α clonality and novel CDR3β recombination of the T-cell receptor. In contrast, hepatocyte apoptosis was triggered, and the transcription of albumin (ALB) was obviously impaired in the deceased patients. We then performed a retrospective study including patients with COVID-19. Serum aspartate aminotransferase (AST) and ALB levels at baseline significantly differed in the deceased cohort. However, AST regression did not decrease the risk of death. ALB recovery indicated clinical improvement, and declining or low serum ALB concentrations were associated with death. Interpretation: This study provides clinical evidence for liver infection with SARS-CoV-2, insight into the impact of SARS-CoV-2 on the liver, and a potential way to evaluate the risk of death via assessing serum ALB concentration fluctuations in patients with COVID-19. Funding: National Key R&D Program of China (2021YFC2300602), National Natural Science Foundation of China (92369110), National Natural Science Foundation of China (U23A20474), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Jinshan District Medical and Health Technology Innovation Fund Project (2023-WS-31).

Background: SARS-CoV-2 infection during pregnancy poses health risks to both mother and fetus. This study investigates neutralizing antibodies (NAbs) against the SARS-CoV-2 JN.1 Omicron subvariant in pregnant women, focusing on responses to natural infection, vaccination, and passive immunity. Methods: A single-center, prospective study collected blood samples from 19 pregnant women at various pregnancy stages and postpartum. NAb titers were analyzed using a pseudovirus neutralization assay, with statistical analyses (p-value

The SARS-CoV-2 infection has spread to various areas of the world, and the number of infected people, seriously ill people, and deaths have increased in 2020∼2023. It is important to suppress the spread of virus from infected people to non-infected people in order to prevent the disease from becoming more severe. To protect widespread of virus, flavor/fragrances composition was selected as a convenient effective material to protect the inhibition. It was previously investigated whether flavor/fragrances composition inhibit the binding between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and host angiotensin converting enzyme 2 (ACE2) in the infection model assay. This binding lead to natural infection of SARS-CoV-2 to tissues. In a previous report, it was found that some Flavor/fragrances compositions strongly inhibited the binding between RBD and ACE2. To clarify whether these flavor/fragrances compositions actually inhibit the infection of SARS-CoV-2, the inhibition assay of infection to VeroE6/TMPRSS2 cells, the inhibition model in vitro, were performed by the treatment of these compositions. Some flavor/fragrances compositions excepting for cinnamyl alcohol, 0.25 %, strongly inhibited the infection of SARS-CoV-2 to VeroE6/TMPRSS2 cells because cinnamyl alcohol could not be completely melted by PBS (pH 7.4) containing 1.5 % Tween 20 and 0.5 % BSA. Among fragrance compounds, cinnamon flavor and cinnamon mint had stronger inhibition effects on the infection effects on SARS-C0V-2 than others. The strategy of using flavor/fragrances compositions such as cinnamon flavor and cinnamon mint may be useful to protect widespread of SARS-CoV-2 in their daily lives.

Objective: The aim of this prospective cohort study is to analyse the humoral and cellular vaccine responses in paediatric heart transplant recipients (HTR, n = 12), and compare it with the response in healthy controls (HC, n = 14). All participants were 5–18 years old and vaccinated with mRNA vaccine against SARS-CoV-2 between December 2021 and May 2022. Methods: The humoral response was measured by quantifying antibody titers against SARS-CoV-2 spike protein (anti-S). The T-lymphocyte phenotype and SARS-CoV2-specific CD4+ and CD8+ T-cell response was studied by multiparametric flow cytometry through peripheral blood mononuclear cells by the quantification of degranulation markers (CD107a) and intracellular cytokines (IFN-γ, TNF-α and IL-2) after in vitro stimulation with SARS-CoV-2 peptides from structural proteins (S, M, N, E) and non-structural viral proteins. Results: After vaccination, humoral response was found in all HTR, although they showed lower levels of anti-S IgG compared to HC (p = 0.003). However, in terms of cellular response, no significant differences were obtained in the prevalence of responders and magnitude of responses between groups. In addition, anti-S IgG levels directly correlated with a higher SARS-CoV-2 specific T-cell response (rho = 0.43; p = 0.027 and rho = 0.45; p = 0.02 for IFN-γ+ and TNF-α+ production of CD8+ T-cells, respectively). Activated T-cell phenotype in HTR was associated with a lower humoral response to SARS-CoV-2 vaccine. Conclusion: HTR had humoral response after vaccination, although they showed lower levels of specific anti-S antibodies compared to HC. There were no significant differences in the SARS-CoV2-specific cellular response between the two groups. Obtaining satisfactory data on this type of response could potentially challenge the current vaccine guideline recommendations.

Background: The SARS-CoV-2 pandemic caused millions of infections worldwide. Among the strategies for effective containment, frequent and massive testing was fundamental. Although sample pooling allows multiplying the installed analysis capacity, the definition of the number of samples to include in a pool is commonly guided more by economic parameters than analytical quality. Methods: We developed a mathematical model to determine the pooling conditions that maximize reagent efficiency and analytical sensitivity. We evaluated 30 samples individually and in 2-sample to 12-sample pools. Using Passing Bablok regressions, we estimated the shift of Ct values in the RT-qPCR reaction for each pool size. With this Ct shift, we estimated sensitivity in the context of the distribution of 1,030 individually evaluated positive samples. Findings: Our results showed that the most significant gain in efficiency occurred in the 4-sample pool, while at pools greater than 8-sample, there was no considerable reagent savings. Sensitivity significantly dropped to 87.18 %–92.52 % for a 4-sample pool and reached as low as 77.09 %–80.87 % in a 12-sample pooling. Conclusions: Our results suggest that a 4-sample pooling maximizes reagent efficiency and analytical sensitivity. These considerations are essential to increase testing capacity and efficiently detect and contain contagious.

Summary: Background: Vaccine co-administration can increase vaccination coverage. We assessed the safety, reactogenicity, and immunogenicity of concomitant administration of Ad26.COV2.S COVID-19 vaccine with seasonal influenza vaccines. Methods: This non-inferiority, Phase 3, randomised, double-blind study enrolled 859 healthy adults and was conducted between 02 November 2021 and 28 November 2022. Participants aged ≥18–64 years were randomised to receive a seasonal quadrivalent standard dose (SD) influenza vaccine (Afluria Quadrivalent, Seqirus) concomitantly with Ad26.COV2.S (Coad_SD) or placebo (0.9% NaCl; Control_SD) on Day 1 and placebo or Ad26.COV2.S on Day 29. Participants aged ≥65-years were randomised to the Coad_SD or Control_SD groups, or to Coad_HD or Control_HD groups that received a seasonal quadrivalent HD (high-dose) influenza vaccine (Fluzone High-Dose Quadrivalent, Sanofi Pasteur Inc) in the same schedules. The primary outcomes were haemagglutinin inhibition titres against the four influenza vaccine strains at Day 29, and SARS-CoV-2 Spike-specific antibodies at Day 29 in the Coad_SD group and Day 57 in the Control-SD group, with a non-inferiority margin (Control-SD group/Coad_SD group) of 1.5. Reactogenicity and safety were assessed in all participants (NCT05091307). Findings: Non-inferiority criteria for concomitant administration in the SD groups were met for SARS-CoV-2 Spike-specific antibodies (ratio 1.11, 95% CI 0.97–1.26) and haemagglutinin inhibition titres for all influenza strains (A/H3N2 1.23, 95% CI 1.05–1.45; B/Victoria 0.99, 95% CI 0.84–1.19; B/Yamagata, 1.03, 95% CI 0.88–1.21) except A/H1N1 (1.28, 95% CI 1.09–1.53) for which the upper limit of the 95% CI was >1.5. Concomitant administration of Ad26.COV2.S and SD influenza vaccine induced robust immune responses in terms of SARS-CoV-2 Spike-specific antibodies and haemagglutinin inhibition to all four influenza strains. Seroconversion and seroprotection rates against all influenza vaccine strains were comparable in the Coad and Control groups. Anti-Spike antibodies 28 days after receiving Ad26.COV2.S were similar whether administered with influenza vaccine or alone. Antibody responses persisted at least 6 months post-vaccination in all groups. The reactogenicity and safety profile following co-administration was consistent with the known safety profiles of the study vaccines. No safety concerns were identified. Coadministration was immunogenic and well tolerated in adults aged ≥65 years who received HD influenza vaccine. Interpretation: Co-administration of seasonal influenza vaccine with Ad26.COV2.S was immunogenic with an acceptable safety profile, supporting co-administration of these vaccines. Funding: Janssen Vaccines & Prevention BV and Biomedical Advanced Research and Development Authority.

Brazil's COVID-19 response has faced challenges due to the continuous emergence of variants of concern (VOCs), emphasizing the need for ongoing genomic surveillance and retrospective analyses of past epidemic waves to reassess and fine tune containment protocols. Rio Grande do Sul (RS), Brazil's southernmost state, has international borders and trades with Argentina and Uruguay, along with significant domestic connections within Brazil. The identification of source and sink transmission chains at national and international scales can identify main hubs and pathways to target future interventions. In this study we investigated the RS state role in the national and international SARS-CoV-2 transmission chains, which has not been fully explored. Nasopharyngeal samples from various municipalities in RS were collected between June 2020 and July 2022. SARS-CoV-2 whole genome amplification and sequencing were performed using high-throughput Illumina sequencing. Bioinformatics analysis encompassed the development of scripts and tools to perform subsampling taking into account epidemiological information to reduce sequencing disparities bias among the regions/countries, genome assembly, and large-scale alignment and phylogenetic reconstruction. We sequenced a total of 1,480 SARS-CoV-2 genomes from RS, covering all major regions. Sequences predominantly represented Gamma (April-June 2021) and Omicron (January-July 2022) lineages. Phylogenetic analysis revealed a regional pattern for transmission dynamics, particularly with Southeast Brazil for Gamma, and a range of inter-regional connections for Delta and Omicron within the country. On the other hand, international and cross-border transmission with Argentina and Uruguay was rather limited. We evaluated the three VOCs circulation over two years in RS using a new subsampling strategy based on the number of cases in each state during the circulation of each VOC. In summary, the retrospective analysis of genomic surveillance data demonstrated that virus transmission was less intense between country borders than within the country. These findings suggest that while non-pharmacological interventions were effective to mitigate transmission across international RS land borders, they were insufficient to contain transmission at the domestic level.

Introduction: Autoantibodies (AAbs) directed against interferon alpha (aIFNα), nuclear antigens (ANAs), anti-cardiolipin (aCL), and anti-beta 2 glycoprotein 1 (aβ2GP1), have been demonstrated to significantly correlate with the severity of acute Coronavirus Disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces these AAbs and whether they are associated with long COVID remains unclear. Methods: The potential induction of aIFNα, ANAs, aCL, and aβ2GP1 by SARS-CoV-2 was assessed by measuring these AAbs in 224 pre- and post-infection paired serum samples from the Johns Hopkins Hospital Emergency Department (JHHED). The relationship between these AAbs and long COVID was assessed using 60 serum samples from participants in the Outpatient SARS-CoV-2 Mild and Asymptomatic Infection Response and Transmission study. Results: We found no evidence that these AAbs were induced in the JHHED cohort and no significant difference in their prevalence between patients with (n = 30) and without (n = 30) long COVID in the OutSMART cohort. Conclusion: These findings do not support the hypotheses that SARS-CoV-2 induces these AAbs or that they are related to long COVID.

Objectives: Children have been largely spared from serious disease through the COVID-19 pandemic despite a high exposure to SARS-CoV-2. Antibody responses to exposure and their role in protecting children from subsequent variant infection remain poorly understood. Methods: This is a prospective cohort study of children in a South African community through ancestral/Beta/Delta/Omicron BA.1/BA.2 and BA.4/BA.5 SARS-CoV-2 waves (March 2020-October 2022). Health seeking behavior/illness was recorded and postwave serum samples measured for immunoglobulin (Ig) G to spike (S) (CoV2-S-IgG) by electrochemiluminescent immunosorbent assay. To estimate the protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter. Results: Despite little disease, 125 per 366 (34.2%) children (median age 6.7 years [interquartile range 5.99-7.4 years]) were seropositive after wave I, rising to 53.6%, 76.0%, and 96.2% and 99.2% after waves II (Beta), III (Delta), and IV and V (Omicron variants), respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection, with the greatest protection for Beta and least for Omicron. The levels of IgG specific for ancestral S antigen that provided a 50% protective threshold for the subsequent wave were lowest for the Beta and highest for the Omicron BA.1/BA.2 wave. In the multivariate analysis, maternal seropositivity (adjusted odds ratio = 2.57 [95% confidence interval: 1.72-3.82]) was strongly associated with child seropositivity. Conclusion: Children responded robustly to successive waves of SARS-CoV-2, mounting IgG responses to S antigen that were protective against subsequent waves. In the absence of vaccination, almost all children were seropositive after wave V but none were hospitalized, suggesting that natural immunity alone may be sufficient to protect children in a pandemic setting.

Summary: Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.1 variant than the XBB variant. This study evaluated the effectiveness and durability of the BNT162b2 XBB.1.5-adapted vaccine against JN.1-related hospitalization during the 2023–2024 season in Europe. Methods: A test-negative case–control study was carried out in adults (≥18 y) hospitalized between 2 October 2023 and 2 April 2024 with severe acute respiratory infection (SARI) within the id.DRIVE partnership. This study included nine sites across Belgium, Germany, Italy, and Spain. Cases had a laboratory-confirmed JN.1 infection or a positive SARS-CoV-2 test with symptom onset during JN.1 predominance; controls had a negative SARS-CoV-2 test and symptom onset during JN.1 predominance. The primary objective was to estimate BNT162b2 XBB.1.5-adapted vaccine effectiveness (VE) against COVID-19 hospitalization. One case was matched with up to four controls, according to symptom onset date and site. Multivariable analyses were adjusted for symptom onset date, age, sex, and number of chronic conditions. Findings: Among 308 test-positive cases and 1117 test-negative controls, BNT162b2 XBB.1.5-adapted VE against hospitalization compared to no vaccination this season was 53.8% (95% CI 38.4–65.4) after a median of 63 days following vaccination. Protection was sustained through five months; VE was 52.2% (95% CI 41.3–61.1) 2 to

Objectives: We estimated vaccine effectiveness (VE) against SARS-CoV-2 infection among a statewide cohort of people with HIV (PWH) and compared the estimates with a matched cohort of people without HIV (PWoH) in South Carolina (SC), USA. Methods: A population-based cohort was retrieved from statewide electronic health records between January 2, 2021, and April 14, 2022, during which several variants were circulating in SC (i.e., Alpha, Delta, Omicron). We compared the odds of vaccination between test-positive cases and test-negative controls using logistic regression models for both SARS-CoV-2 infection and severe COVID-19 outcomes. The VE was derived as (1 − adjusted odds ratio) × 100%. Results: A total of 7279 test episodes in PWH and 72,790 matched test episodes in PWoH were included for analysis, representing 6561 unique PWH and 67,521 unique PWoH. The peak level of VE against SARS-CoV-2 infection occurred 7-59 days after receipt of the second dose of vaccine (PWH: 61.20%; PWoH: 67.09%), followed by a waning protective effect 90-119 days after the second dose in both PWH (35.80%) and PWoH (47.57%), where PWH had a proportionally lower and declined faster VE. Regarding the VE against severe outcomes of SARS-CoV-2 infection, a relatively higher level of protection was maintained in both populations (complete primary series: PWH: 69.06%; PWoH: 60.63%). Conclusions: A complete primary series of COVID-19 vaccines offered significant protection against SARS-CoV-2 infection and severe outcomes in both PWH and PWoH populations, although this wanes with time. However, the estimate of VE against SARS-CoV-2 infection appeared lower in PWH than in PWoH and the degree of waning over time was relatively quicker in PWH.

Objectives: Influenza-like-illness (ILI) is a commonly used symptom categorization in seasonal disease surveillance focusing on influenza in community and clinical settings. However, SARS-CoV-2 often causes presentation with a similar symptom profile. We explore how SARS-CoV-2-positive individuals can influence surveillance trends for the World Health Organization, the United States Centre for Disease Control, and the European Centre for Disease Control (ECDC) ILI criteria. Methods: Harnessing the Winter COVID-19 Infection Study in England, a cohort study, the prevalence of different ILI definitions is modeled using multilevel regression and poststratification using age and spatial stratifications with temporal smoothing. Trends over time across stratifications were compared for SARS-CoV-2 positive and negative individuals to understand differences in ILI trends. Symptom presentation across positive and negative SARS-CoV-2 cases were compared. Results: SARS-CoV-2 symptom profiles are shown to overlap with the ILI case definitions, particularly for “cough” and “fever”, causing SARS-CoV-2 positive individuals to be frequently detected as ILI cases. The trend of SARS-CoV-2 positives is a substantial component of the ILI-modeled trend, driving an earlier perceived peak in prevalence. The ECDC symptom definition was most influenced by SARS-CoV-2 positive individuals. Conclusions: Using a large community cohort we show how SARS-CoV-2 can impact ILI surveillance trends. SARS-CoV-2 makes up a substantial part of the community ILI burden and public health messaging should reflect this when discussing ILI. We show ILI is no longer a strong proxy for influenza activity alone.

Objectives: We evaluated all-cause healthcare utilization among those with vaccine-associated myocarditis, compared to vaccinees without postvaccination myocarditis. Methods: We conducted a retrospective cohort study in individuals aged 12 and older who received COVID-19 mRNA vaccination in British Columbia. Exposure was defined as an ED visit or hospitalization for myocarditis within 21 days postvaccination. The primary outcome was healthcare utilization. Ratios of rate ratios (RRRs) for exposure-associated healthcare utilization were calculated using a difference-in-differences (DiD) analysis. Results: In the postindex period, the exposed and unexposed groups showed substantial utilization rate difference (RD = 15.30 [95% CI, 14.47-16.13). A 51% overall increase in healthcare utilization was observed over 18 months among exposed individuals (RRR, 1.51 [95%CI, 1.08-2.11]). In the initial six months, healthcare utilization surpassed the 18-month estimate, exhibiting a 125% increase (RRR, 2.25 [95%CI, 1.43-3.52]), while the last 12 months showed no statistically significant change (RRR, 1.03 [95%CI, 0.72-1.47]). An additional 9.1 (95%CI, 8.53-9.71) visits per person were attributed to vaccine-associated myocarditis over 18 months (total excess = 938.26 healthcare visits). Conclusion: The initial surge in healthcare visits postexposure, mainly outpatient follow-ups, followed by a return to baseline rates, indicates a positive prognosis and supports the vaccine's safety profile.

Background: There have been over 670 million confirmed cases of SARS-CoV-2 infection globally, resulting in over 6.87 million deaths. With approximately 0.1 %−6.8 % experiencing reinfection. This retrospective cohort study aimed to compare the risk of short-term circulatory and respiratory sequelae between SARS-CoV-2 reinfection and initial infection, and assess the impact of vaccination. Method: Data from the TriNetX US Collaborative network (2020–2022) were used to create two cohorts based on reinfection status. The main outcome assessed were medical utilization, circulatory and respiratory symptoms, and circulatory and respiratory diseases. The Kaplan-Meier method was used to compare the risks between two cohorts. Four subgroup analyses (vaccination status, age, sex, race) and six sensitivity analyses (rigorous definition, modified exclusion criteria, treatment, different COVID-19 variants timeline, address survivorship bias, and E-value calculation) were also conducted. Results: The reinfection cohort showed a significant reduction in medical utilization [ Hazard ratio, HR: 0.867, (95 % confidence interval, CI:0.839–0.896) for hospitalization, 0.488 (0.418–0.570) for critical care services, and 0.476 (0.360–0.629) for mechanical ventilation], lower risk of circulatory diseases [ HR: 0.701 (95 % CI:0.637–0.772), 0.695 (0.583–0.829), 0.660 (0.605–0.719), 0.741 (0.644–0.854), 0.614 (0.535–0.705), and 0.758 (0.656–0.876) for ischemic heart disease, inflammatory heart disease, dysrhythmias, venous thromboembolism, other cardiac disorders, and cerebrovascular diseases, respectively], and lower risk of respiratory diseases such as pneumonia, other acute lower respiratory infections, asthma, and hypoxemia [HR: 0.302 (95 % CI: 0.273–0.333), 0.811 (0.686–0.958), 0.791 (0.735–0.850), and 0.392 (0.338–0.455), respectively]. The vaccinated reinfection cohort showed no significant differences in medical utilization, circulatory diseases, or respiratory conditions but had a higher risk of breathing abnormalities. breathing abnormalities [HR: 1.195 (95 % CI:1.087–1.313)]. Conclusions: The individuals who experienced reinfection exhibited milder short-term sequelae in the circulatory and respiratory systems. Vaccine administration protects against cardiovascular or respiratory systems.

Introduction: Refugee settings may increase the risk of SARS-CoV-2 infection and death, yet data on the response to the pandemic in these populations is scarce. Methods: We describe interventions to mitigate SARS-CoV-2 transmission in Dadaab Refugee Camp Complex, Kenya and performed descriptive analyses using March 2020 to December 2022 data from Kenya's national SARS-CoV-2 repository and line list of positive cases maintained by United Nations High Commissioner for Refugees (UNHCR). We calculated case fatality rates (CFR) and attack rates per 100,000 (AR) using the 2019 national census and population statistics from UNHCR and compared them to national figures. Results: SARS-CoV-2 infection was first reported in April and May 2020, among host community members and refugees respectively. Of 964 laboratory-confirmed cases, 700 (72.6 %) were refugees. The AR was 82.7 (95 % CI 72.6–92.8) for host community members, 228.3 (95 % CI 211.3–245.4) for refugees and 721.1 (95 % CI 718.7–723.5) nationally. The CFR was 1.5 % (95 % CI 0.15–3.18) for host community members, 1.76 % (95 % CI 1.71–1.80) nationally and 7.4 % (95 % CI 5.4–9.4) for refugees.Mitigation measures implemented by the Government of Kenya, UNHCR and partners during the pandemic included multisectoral coordination, movement restrictions, mass gathering bans, and health promotion. Social distancing, symptom screening and mandatory mask usage were enforced during mass gatherings. Testing capacity was bolstered, quarantine and isolation facilities established, and vaccination initiated. Conclusions: Despite a low AR and UNHCR's swift and comprehensive response, refugees' CFR was high, underscoring their vulnerability and need for targeted interventions during epidemic responses.

Summary: Background: As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi). Methods: In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi. Findings: Between December 17, 2021, and June 20, 2023, 456 infection-naïve patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138–45,233) vs 36,341 IU/ml (11,887–53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176–54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naïve patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494–50,211)) compared to the fourth dose (7304 IU/ml (3245–17,260), p

AIM: We aimed to test the cross-neutralizing antibody response of hospital healthcare workers (HCWs) vaccinated with CoronaVac and/or BioNTech against SARS-CoV-2 Omicron variant that appeared in February 2024 in Turkey. BACKGROUND: HCWs are at risk for exposure to many viruses because of their contact with infectious patients. As SARS-CoV-2 Omicron and its subvariants are increasing in prevalence worldwide, HCWs are still dealing with it. METHODS: SARS-CoV-2 isolates, collected from the nasopharyngeal samples of COVID-19 patients, were propagated in Vero-E6 cells and the viral titration was carried out by PFU/mL, TCID50/mL assays, and RT-qPCR. The whole genome of variants was sequenced. We tested the protectivity of 102 serum samples of HCWs, collected between September and October 2023, through serum neutralization experiments. Viral RNA loads in the cell culture supernatants after infection were calculated by RT-qPCR. Furthermore, anti-SARS-CoV-2 antibodies (IgG) were screened by ELISA. The results were compared with the data of the Omicron variant, isolated in 2021 and used as a control group. RESULTS: The delta(Ct) values of RT-qPCR results of the new variant were found to be statistically lower than those of control variant (9.36±1.28 vs. 11.82±1.72, p

As COVID-19 has become endemic, SARS-CoV-2 variants are becoming increasingly diverse, underscoring the escalating importance of global genomic surveillance. This study analyzed 86,762 COVID-19 samples identified in the Republic of Korea from September 2022 to November 2023. The results revealed a consistent increase in the prevalence of the XBB variants following the dominance of BN.1, with various XBB sub-lineages co-circulating in the Republic of Korea. The overall nucleotide diversity (π) among the SARS-CoV-2 genomes was 0.00155. Evolutionary analysis revealed that the average time interval between the first detection and estimated date of the most recent common ancestor of Korean XBB sub-lineages was 47 d, suggesting that the novel variants were efficiently identified in the Korean surveillance system. The mutation rate was determined to be in the range of 5.6 × 10–4 to 9.1 × 10–4 substitutions/site/year. In conclusion, this study provides insights into the genetic diversity and evolutionary interpretation of the XBB sub-lineages during the XBB wave in the Republic of Korea, highlighting the importance of continued genomic surveillance for emerging variants.

Background: Biomonitoring is an essential activity for identifying possible vectors and reservoirs of pathogens and predicting potential outbreaks. Wild red foxes are present in both sylvatic and synanthropic environments, making them potential carriers of zoonotic pathogens. Experimental studies have shown that both coyotes and red foxes can transmit SARS-CoV-2. This study aimed to assess the prevalence and seroprevalence of SARS-CoV-2 in wild red foxes hunted in northern Poland. Methods: Oral swabs, blood clots or heat tissue samples were collected from 292 red foxes hunted in northern Poland. We used both molecular (RT-PCR) and serological (IFA) approaches to detect SARS-CoV-2 infections in the sampled animals. Results: We did not find any evidence of SARS-CoV-2 infection in the collected samples, using both molecular and serological methods. Conclusions: Despite foxes having frequent contact with humans, human waste, and other animals, they do not appear to participate in the circulation of the SARS-CoV-2 virus in our geographical region. Nevertheless, we believe that continuous biomonitoring should be performed to assess the SARS-CoV-2 epidemiological situation in the wild.

There have been reports of the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to various mammalian species. Some infected animals show clinical signs and may even die in rare cases. Outbreaks of SARS-CoV-2 have been reported in zoos where susceptible animals are bred in high population densities. However, there have been few reports of omicron variant outbreaks in zoo animals. From late 2022 to 2023, an outbreak of the SARS-CoV-2 omicron variant occurred in one Japanese zoo. A total of 24 lions were housed in the zoo; 13 of them showed respiratory symptoms, and the three oldest lions died. Molecular and histopathological analyses revealed that the deceased lions were infected with SARS-CoV-2 omicron BF.7.15. Virus-neutralization tests showed that all 21 lions were positive for antibodies against the omicron variant, but not against the delta variant. In addition, three tigers and one bear in the same or neighboring building as the lions possessed antibodies against the omicron variant. This is a very rare report on the outbreak of a SARS-CoV-2 omicron variant infection that resulted in the death of animals. This finding demonstrates the importance of continuous countermeasures to protect non-vaccinated animals from SARS-CoV-2 infection.

Introduction: SARS-CoV-2 may transmit across vaccinated cohorts during practical clinical examinations. We sought to assess the feasibility of facemask sampling (FMS) to identify individuals emitting SARS-CoV-2 during a mock PACES exam. Methods: In May 2022 we recruited participants from a mock PACES examination in Leicester, UK. Following a negative lateral flow test assay, all participants wore modified facemasks able to capture exhaled virus during the assessment (FMS). A concomitant upper respiratory tract sample (URTS) was provided prior to FMS. Exposed facemasks were processed by removal and dissolution of sampling matrices fixed within the mask and cycle thresholds values quantified by RT-qPCR. Participants were asked to grade statements regarding the comfort, effort, ethics and communication when providing FMS; laboratory technicians were asked to grade key statements surrounding suitability of samples for processing. Results: 34 participants provided concomitant URTS and FMS during the examination. One participant was positive for SARS-CoV-2, with a cycle threshold value of 22.5 on URTS, but negative (no viral RNA detected) on FMS; no transmission to others was identified from this individual. Participants responded positively to statements regarding FMS describing all four domains; however, 69% of participants felt that a positive result from FMS alone was insufficient for diagnosis and that further tests were required. All but one FMS sample was suitable for processing. Discussion: FMS during PACES exams are acceptable among participants and samples provided are suitable for processing. Our results demonstrate feasibility of FMS within practical examination settings and support the further assessment of FMS as a scalable tool that can be compared with URTS to identify those who are infectious.

Background: During the COVID-19 pandemic the aetiology of respiratory illnesses were narrowed to SARS-CoV-2. This prevented diagnosis of other pathogens and patients were not notified of the accurate diagnosis of their illnesses when SARS-CoV-2 was absent. It is therefore important to look back and determine what else was present but was missed. Objective: This retrospective study sought to gain insights into prevalence of respiratory syncytial virus (RSV) and influenza A alongside SARS-CoV-2 in patients who reported with clinical symptoms of respiratory illnesses. Methods: Samples from patients who had reported of respiratory symptoms were selected at random from a pool. RNA was extracted and RT-PCR was performed for SARS-CoV-2, RSV and Influenza A in parallel. Data on the clinical symptoms was extracted from case-base forms and analysed. Results: Of the 400 symptomatic samples tested, prevalence of SARS-CoV-2, influenza A and RSV was 20.3 %, 2.0 % and 0.5 % respectively. Only one sample tested positive for SARS-CoV-2 and influenza A. About 77 % of the symptomatic cases did not test positive for any of the three agents. Cough (79 %) was the most common symptom followed by fever and chills, headache, sore throat and runny nose. Conclusion: The large proportion of symptomatic cases that tested negative for all three respiratory viruses raises a flag and a need for more investigations into the actual burden of respiratory aetiologic agents during the pandemic. With the low levels of co-infections, parallel testing may not be needed however, a strong case for multiplex tests for respiratory agents exists.

The mRNA vaccines have proven to be very effective in preventing severe disease and death from SARS-CoV-2 in the general population. However, in patients with chronic kidney disease (CKD) in dialysis or with kidney transplants (KT) the vaccine responses vary, with severe breakthrough infections as a consequence. In this intervention study we investigated the magnitude and quality of the responses to mRNA vaccination administered prior to kidney replacement therapy (KRT). Twenty patients with CKD G4/5 and nine healthy controls were followed for 12 months after receiving two doses of BNT162b2 four weeks apart and a booster dose after 3–6 months. Induction of anti-Spike and anti-RBD IgG in plasma followed the same kinetics in CKD patients and controls, with a trend towards higher titers in controls. In accordance, there was no differences in the establishment of Spike-specific memory B-cells between groups. In contrast, the CKD patients showed lower levels of anti-Spike IgG in saliva and Spike-specific CD8+ T-cells in blood, possibly influencing the capacity of viral clearance which can contribute to an elevated risk of severe breakthrough infections. In conclusion, we found that CKD patients, despite having a reduced mucosal and cytotoxic immunity to BNT162b2, demonstrated a serological response in plasma similar to healthy controls. This suggests that immunization prior to RRT is efficient and motivated. (EudraCT-nr 2021-000988-68).

Background: Early in the COVID-19 pandemic, convalescent plasma (CP) emerged as a potentially effective treatment neutralising SARS-CoV-2. Early CP therapy with high neutralising antibody (NAb) titre may benefit COVID-19 outpatients and, in sufficient quantities even some hospitalised patients. This study details the process of setting up a CP bank, containing high- and low-titre CP for a clinical trial. Study design and methods: We identified 18–65-year-old convalescents with SARS-CoV-2 NAb titres of ≥1:40 in microneutralisation test (MNT). Following eligibility pre-screening, the Finnish Red Cross Blood Service (FRCBS) determined suitability as CP donors. Results: Of the 6466 COVID-19 convalescents contacted, 1481 provided serum, with 851 (57.5 %) exhibiting NAb titres ≥1:40. Participation barriers included reluctance, advanced age and, for women, insufficient body size. Of the volunteers, 125 were evaluated at FRCBS, with major exclusions for HLA antibodies (42 women), interferon antibodies (five men), and NAb titres waning below 1:20 (16 participants). Finally, 70 underwent plasmapheresis, resulting in 50 suitable CP donors (0.8 % of initial contacts and 3.4 % of those tested for NAb). Discussion: The process of setting up a CP bank proved challenging. Excessive laboratory workloads during a pandemic hamper their ability to conduct MNT, underscoring the need for rapid screening tests. Only a small proportion of our convalescents exhibited high-titre CP, this fraction declining over time because of waning immunity. Strict plasmapheresis criteria further constrained donor eligibility. Establishing a plasma bank requires meticulous planning to maximize efficiency. Detailed insights from current experiences may prove critical in future pandemics before other remedies and vaccines become available.

Objective: The COVID-19 pandemic highlighted and exacerbated health inequities worldwide. While several studies have examined the impact of individual social factors on COVID infection, our objective was to examine how interactions of social factors were associated with the risk of testing positive for SARS-CoV-2 during the first two years of the pandemic. Study design and setting: We conducted an observational cohort study using linked health administrative data for Ontarians tested for SARS-CoV-2 between January 1st, 2020, and December 31st, 2021. We constructed multivariable models to examine the association between SARS-CoV-2 positivity and key variables including immigration status (immigrants vs. other Ontarians), and neighbourhood variables for household size, income, essential worker status, and visible minority status. We report main and interaction effects using odds ratios and predicted probabilities, with age and sex controlled in all models. Results: Of 6,575,523 Ontarians in the cohort, 88.5 % tested negative, and 11.5 % tested positive for SARS-CoV-2. In all models, immigrants and those living in neighbourhoods with large average household sizes had greater odds of testing positive for SARS-CoV-2. The strength of these associations increased with increasing levels of neighbourhood marginalization for income, essential worker proportion and visible minority proportion. We observed little change in the probability of testing positive across neighbourhood income quintiles among other Ontarians who live in neighbourhoods with smaller households, but a large change in probability among other Ontarians who live in neighbourhoods with larger households. Conclusion: Our study found that SARS-CoV-2 positivity was greater among people with certain combinations of social factors, but in all cases the probability of testing positive was consistently greater for immigrants than for other Ontarians. Examining interactions of social factors can provide a more nuanced and more comprehensive understanding of health inequity than examining factors separately.

Background: Preliminary data across the globe shows that the AZD1222 recombinant vaccine was highly effective in preventing not only the symptoms but also the transmission of the SARS-CoV-2 virus. In Ghana, data on the immune response generated by different vaccination doses is lacking. The present study aimed to compare the anti-SARS-CoV-2 antibody response among single and double-vaccinated versus unvaccinated individuals. Methods: A case-control design was employed for this study. Seventy-nine participants (35 vaccinated, 44 unvaccinated) were recruited from the Sunyani West municipality and screened for the presence of SARS-CoV-2 specific IgG and IgM antibodies in plasma samples using a Standard COVID IgG and IgM Combo immunoassay test. Data analysis was carried out with STATA (version 21). Results: The current study showed that mean IgG levels among vaccine groups (Group 1: Not vaccinated, Group 2: 1 dose, Group 3: 2 doses) differed significantly (F2, 76=11.457, p

Background: Older adults remain vulnerable to COVID-19 waves, particularly in low-income countries with health disparities, so the discovery and validation of accessible clinical tools are required. Despite the expected changes associated with aging, little has been studied on ferritinemia as a prognostic marker, specifically in this population. Objective: Evaluate the use of serum ferritin levels at hospital admission as a prognostic marker in older adults hospitalized for COVID-19. Material and methods: This monocentric study included people over 60 hospitalized for COVID-19 between 2021 and 2022. Disease presence was assessed with polymerase chain reaction and ferritin with spectrophotometry. Multiple logistic regression models, as well as ROC and Kaplan-Meier curves, were used. Results: In 239 older adults, the association between serum ferritin and mortality was modified by the presence of clinical severity data at admission, being a poor prognosis factor only for those with severe COVID-19 (OR=2.82, p = 0.028, controlling for age and immunization doses). The best cut-off point was 355 ng/dl (Sensitivity: 88.3 %; Specificity: 27.4 %). However, there were no differences in survival curves. Conclusions: Serum ferritin levels could help guide therapeutic decisions in older adults with severe COVID-19 but do not predict mortality independently.

Background: Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking. Objective: To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms. Methods: 223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue. Results: A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (n = 37,16.6%), cough (n = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56+ cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae. Conclusion: Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56+ NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic. After the success of therapeutics and worldwide vaccination, the long-term sequelae of SARS-CoV-2 infections are yet to be determined. Common symptoms of COVID-19 include the loss of taste and smell, suggesting SARS-CoV-2 infection has a potentially detrimental effect on neurons within the olfactory/taste pathways, with direct access to the central nervous system (CNS). This could explain the detection of SARS-CoV-2 antigens in the brains of COVID-19 patients. Different viruses display neurotropism that causes impaired neurodevelopment and/or neurodegeneration. Hence, it is plausible that COVID-19-associated neuropathologies are directly driven by SARS-CoV-2 infection in the CNS. Microglia, resident immune cells of the brain, are constantly under investigation as their surveillance role has been suggested to act as a friend or a foe impacting the progression of neurological disorders. Herein, we review the current literature suggesting microglia potentially been a susceptible target by SARS-CoV-2 virions and their role in viral dissemination within the CNS. Particular attention is given to the different experimental models and their translational potential.

According to sparse information from various countries, the seasonal influenza virus circulation has drastically decreased during the COVID-19 pandemic. Here, we show the cross-reactivity of anti-SARS-CoV-2 antibodies against influenza viruses. Plasma samples were collected from 311 SARS-CoV-2 infected individuals. The samples were tested for antibody titers against SARS-CoV-2 by ELISA and seasonal influenza virus strains (influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria) using a Hemagglutination Inhibition Assay (HAI). In addition, SARS-CoV-2 antibody-positive but Influenza antibody-negative samples (n = 16) were investigated to determine the SARS-CoV-2 antibody-neutralizing potential against influenza viruses by microneutralization (MN) assay. The SARS-CoV-2 genomes were sequenced using Illumina next-generation sequencing, and an in-silico protein structural analysis was performed to identify epitope and antibody binding similarities between SARS-CoV-2 and influenza viruses. Among 16 samples that didn't contain antibodies against Influenza A strains (H1N1 and H3N2), five showed high (MN titer≥20), and six showed moderate (MN titer≥10) capability to neutralize Influenza A. Subsequent in-silico analysis revealed that most efficient binding (>8 kcal/mol) was found between the antibodies of SARS-CoV-2 delta variant (ΔG) with influenza A/H1N1 HA (Hemagglutinin), A/H3N2 HA, A/H1N1 NA (Neuraminidase), and A/H3N2 NA glycoproteins with −12.4, −9.3, −10.1, and −11.7 kcal/mol, respectively. This investigation revealed that neutralizing antibodies of the delta variant cross-reacted with the Influenza A virus, which might protect against influenza viruses and reduce and shift the seasonal influenza circulation during the COVID-19 pandemic. Our findings warrant further study to explain the probable mechanisms of this cross-reactivity.

In 2022, the US Centers for Disease Control and Prevention commissioned the National Academies of Sciences, Engineering, and Medicine to assess the role of community-level wastewater-based epidemiology (WBE) beyond COVID-19. WBE is recognized as a promising mechanism for promptly identifying infectious diseases, including COVID-19 and other novel pathogens. An important conclusion from this initiative is the critical importance of maintaining equity and expanding access to fully realize the benefits of wastewater surveillance for marginalized communities. To address this need, we propose an optimization framework that strategically allocates wastewater monitoring resources at the wastewater treatment plant (WWTP) level, ensuring more effective and equitable distribution of surveillance efforts to serve underserved populations.The purpose of the framework is to obtain a balanced spatial distribution, inclusive population coverage, and efficient representation of disadvantaged groups in the allocation of resources for WBE. Furthermore, the framework concentrates on areas with high population density and gives priority to vulnerable regions, as well as identifying signals that display significant variations from other monitored sources. The optimization objective is to maximize a weighted combination of these critical factors. This problem is formulated as an integer optimization problem and solved using simulated annealing. We evaluate various scenarios, considering different weighting factors, to optimize the allocation of WWTPs with monitoring systems. This optimization framework provides an opportunity to enhance WBE by providing customized monitoring strategies created to address specific priorities and situations, thus enhancing the decision-making processes in public health responses.