One master and two servants: One Zr(â £) with two ligands of TCPP and NH2-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application.

Here we put forward an innovative "one master and two servants" strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH2-BDC (TCPP@UiO-66-NH2) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH2-BDC) with Zr clusters. TCPP@UiO-66-NH2 has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer. Importantly, TCPP@UiO-66-NH2 has a higher and more stable ECL signal. To further improve the sensitivity of the sensor, we use polydopamine-coated manganese dioxide (PDA@MnO2), which has a double quenching effect, as the quencher. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-N) is one of the ideal markers for the early diagnosis of COVID-19, and its sensitivity detection is of great significance for the prevention and treatment of COVID-19. Thus, we constructed a quenching-type ECL sensor for the ultrasensitive detection of the SARS-CoV-2-N. Its linear range is 10 fg/mL∼1 µg/mL and the calculated detection limit is 1.4 fg/mL (S/N = 3). The spiked recoveries are 97.40-103.8%, with the relative standard deviations (RSD) under 3.0%. More importantly, the technique offers a viable way to identify and diagnose viral infections early.

Revolutionizing SARS-CoV-2 omicron variant detection: Towards faster and more reliable methods.

The emergence of the highly contagious Omicron variant of SARS-CoV-2 has inflicted significant damage during the ongoing COVID-19 pandemic. This new variant's significant sequence changes and mutations in both proteins and RNA have rendered many existing rapid detection methods ineffective in identifying it accurately. As the world races to control the spread of the virus, researchers are urgently exploring new diagnostic strategies to specifically detect Omicron variants with high accuracy and sensitivity. In response to this challenge, we have compiled a comprehensive overview of the latest reported rapid detection techniques. These techniques include strategies for the simultaneous detection of multiple SARS-CoV-2 variants and methods for selectively distinguishing Omicron variants. By categorizing these diagnostic techniques based on their targets, which encompass protein antigens and nucleic acids, we aim to offer a comprehensive understanding of the utilization of various recognition elements in identifying these targets. We also highlight the advantages and limitations of each approach. Our work is crucial in providing a more nuanced understanding of the challenges and opportunities in detecting Omicron variants and emerging variants.

A triple-aptamer tetrahedral DNA nanostructures based carbon-nanotube-array transistor biosensor for rapid virus detection.

Outbreaks of infectious viruses cause enormous challenges to global public health. Recently, the coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely threatened human health and resulted in the global pandemic. A strategy to detect SARS-CoV-2 with both fast sensing speed and high accuracy is urgently required. Here, rapid detection of SARS-CoV-2 antigen using carbon-nanotube-array-based thin-film transistor (CNT-array-based TFT) biosensors merged with tetrahedral DNA nanostructures (TDNs) and triple aptamers is demonstrated for the first time. Compared with CNT-network-based TFT biosensors and metal-electrode-based CNT-TFT biosensors, the response of CNT-array-based TFT biosensors can be enhanced up to 102% for SARS-CoV-2 receptor-binding domain (RBD) detection, which is supported by its sensing mechanism. By combining TDNs with triple aptamers, the biosensor has realized the wildtype SARS-CoV-2 RBD detection in a broad detection range spanning eight orders of magnitude with a low limit of detection (LOD) of 10 aM (6 copies/µL) owing to the improved protein capture efficiency. Moreover, the triple-aptamer biosensor platform has achieved the detection of SARS-CoV-2 Omicron RBD in a low LOD of 6 aM (3.6 copies/µL). Additionally, the CNT-array-based TFT biosensors have exhibited excellent specificity, enabling identification among SARS-CoV-2 antigen, SARS-CoV antigen and MERS-CoV antigen. The platform of CNT-array-based TFT biosensors combined with TDNs and triple aptamers provides a high-performance and rapid approach for SARS-CoV-2 detection, and its versatility by altering specific aptamers enables the possibility for rapid virus detection.

Phenol red as electrochemical indicator for highly sensitive quantification of SARS-CoV-2 by loop-mediated isothermal amplification detection.

The current COVID-19 pandemic has made patent the need for rapid and cost-effective diagnostic tests, crucial for future infectious outbreaks. Loop-mediated isothermal amplification (LAMP) is a promising and decentralized alternative to qPCR. In this work we have developed a sensitive, fast, and simple innovative methodology for quantification of SARS-CoV-2 RNA copies, combining reverse-transcription LAMP with electrochemical detection. This is based on the oxidation of phenol red (PR), a visual and electroactive LAMP indicator, which oxidation peak potential (Ep) changes with the progress of the LAMP reaction. Using that Ep shift as analytical signal, a calibration curve was obtained for fragment N1 copies of SARS-CoV2 (which provided better results than N or S fragments), with a potential shift of 16.2 mV per order of magnitude, and a practical limit of detection of 21 copies·µL-1. Moreover, the precision of Ep is excellent (RSD < 2%): 557 ± 5 mV for negative and 602 ± 7 mV for positive (2148 N fragment RNA copies·µL-1·-1) LAMP controls. This methodology has been applied to the analysis of nasopharyngeal swab samples, resulting in total concordance with clinical RT-qPCR results. Advances towards fully decentralization have been achieved by designing and fabricating a small portable heater for isothermal procedures, obtaining comparable results to those from a commercial benchtop thermal cycler.

A facile electrochemical biosensor for coronavirus RNA assay with silver deposition.

Coronaviruses are highly infectious and pose a serious threat to human and animal healths. In this work, a facile electrochemical method based on Exonuclease III (Exo III) catalyzed digestion and silver deposition is developed for coronavirus RNA analysis. A magnetic separation procedure is performed to specifically identify target sequence and release single-stranded DNA modified gold nanoparticles (AuNPs). The nanoparticles can thus be immobilized at a screen-printed electrode and catalyze silver deposition for signal readout. This method allows sensitive analysis of PEDV and SARS-CoV-2 RNAs in the concentration range from 1 to 1000 nM with the limits of detection as low as 0.47 nM and 0.17 nM, respectively. Good specificities are demonstrated. Thus, the proposed method may have great potential use in the applications of coronaviruses analysis.

Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients.

Background: Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients. Methods: In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded. Results: After the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range [IQR] 7.2-402.8) to 1,612.1 (IQR 153.9-5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels (<400 AU/mL) post-third vaccination were a risk factor for symptomatic breakthrough infection (hazard ratio [HR]=3.46, P<0.001). Anti-RBD IgG levels <200 AU/mL were a critical risk factor for hospitalization (HR=36.4, P=0.007). Conclusions: Low anti-spike IgG levels after third vaccination in kidney transplant recipients were associated with symptomatic breakthrough infection and, particularly, with hospitalization during the Omicron surge. These data can be used to identify patients requiring additional protective measures, such as passive immunization using monoclonal antibodies.

Bioscreening specific peptide-expressing phage and its application in sensitive dual-mode immunoassay of SARS-CoV-2 spike antigen.

Biorecognition components with high affinity and selectivity are vital in bioassay to diagnose and treat epidemic disease. Herein a phage display strategy of combining single-amplification-panning with non-amplification-panning was developed, by which a phage displaying cyclic heptapeptide ACLDWLFNSC (peptide J4) with good affinity and specificity to SARS-CoV-2 spike protein (SP) was identified. Molecular docking suggests that peptide J4 binds to S2 subunit by hydrogen bonding and hydrophobic interaction. Then the J4-phage was used as the capture antibody to establish phage-based chemiluminescence immunoassay (CLIA) and electrochemical impedance spectroscopy (EIS) analytical systems. The as-proposed dual-modal immunoassay platform exhibited good sensitivity and reliability in SARS-CoV-2 SP and pseudovirus assay. The limit of detection for SARS-CoV-2 SP by EIS immunoassay is 0.152 pg/mL, which is dramatically lower than that of 42 pg/mL for J4-phage based CLIA. Further, low to 40 transducing units (TU)/mL, 10 TU/mL SARS-CoV-2 pseudoviruses can be detected by the proposed J4-phage based CLIA and electrochemical immunosensor, respectively. Therefore, the as-developed dual mode immunoassays are potential methods to detect SARS-CoV-2. It is also expected to explore various phages with specific peptides to different targets for bioanalysis.

Temperature-insensitive label-free SARS-CoV-2 spike protein detection based on complementary refractive index and temperature dependence of multi-mode interference and grating resonance.

We demonstrated temperature-insensitive, label-free detection of SARS-CoV-2 spike protein (SSP) by harnessing the complementary refractive index and temperature dependence of multi-mode interference (MMI) created by a no-core fiber (NCF) and phase-matched resonance generated by a long-period fiber grating (LPFG). To combine MMI and grating resonance, primarily sensitive to the surrounding medium refractive index (SMRI) and ambient temperature, respectively, a fiber-optic transducer was fabricated by splicing an NCF segment with an LPFG inscribed on double-clad fiber. The transducer was functionalized with human ACE2 receptors to selectively capture SSP. The functionalized sensor head exhibited high SSP selectivity, with overall average wavelength displacements of ∼253.33 and ∼160.00 pm in PBS and saliva, respectively, for SSP with concentrations ranging from 1 to 104 ng/mL. These spectral shifts are associated with localized SMRI modulations on the sensor surface induced by specific binding between SSP and ACE2. We also examined the cross-reactivity of the sensor head for MERS-CoV spike protein to confirm its SSP specificity. Moreover, we proved the capability of temperature-independent SSP detection and ambient temperature measurement by scrutinizing the temperature effect on the sensor performance. Our functionalized fiber transducer showed great promise as a temperature-insensitive and portable platform for rapid SSP detection.

Fabrication of flexible electrospinning nano-fiber membrane for detection of respiratory tract transmission virus based on SERS.

The application of flexible sensors in the biomedical field is deepening. It is of great significance to develop flexible wearable sensors which are more in line with the needs of the public. A flexible polylactic acid membrane fabric was prepared by electrospinning method. The membrane was used as SERS active substrate by screen printing capture probe which combine Au nanoplates with antibodies to the target substance. Thioglycolic acid-labeled silver nanoparticles coupled with antibodies as SERS nanotags. The target substance can be fixed between the capture probe and SERS nanotags. Due to the high specific surface area between the spinning, the adhesion rate of the capture probe is higher than that of the rigid substrate, and the enrichment and hypersensitivity detection of the object to be tested could be realized. The membranes prepared are flexible, wearable, portable, highly biocompatible, and can be mass-produced for high-throughput detection. We then applied the sensor to the detection of SARS-CoV-2 with detection limits as low as 10 TU/mL. This membrane as a SERS substrate can offer a fast and non-invasive reference for the early diagnosis of respiratory infectious diseases similar to COVID-19.

Regional Update, Influenza and Other Respiratory Viruses. Epidemiological Week 34 (1 September 2023)

[WEEKLY SUMMARY]. North America: Influenza activity has remained at low levels. Over the past 4 epidemiological weeks (EW), the predominant influenza viruses have been influenza A(H1N1)pdm09, with concurrent circulation of influenza B/Victoria. Respiratory syncytial virus (RSV) activity has remained at low levels. SARS-CoV-2 activity has shown an increase over the last 4 EWs and continues to circulate at moderate levels. Cases of influenza-like illness (ILI) and severe acute respiratory infections (SARI) have increased, with a rising proportion of cases testing positive for SARS-CoV-2. Caribbean: Influenza activity continues to exhibit a declining trend over the past 4 EWs. During this period, the predominant influenza viruses have been B/Victoria, with lesser circulation of influenza A, primarily A(H1N1)pdm09. RSV activity has remained low. SARS-CoV-2 activity shows an increasing trend with intermediate to high levels of circulation. ILI and SARI cases have demonstrated a declining trend over the past 4 EWs. Central America: Influenza activity continues to decrease over the past 4 EWs. During this period, the predominant influenza viruses have been influenza B/Victoria, with concurrent circulation of influenza A, mainly A(H1N1)pdm09, and to a lesser extent, influenza A(H3N2). RSV activity has shown a decrease in the last EWs but remains at medium-high levels of circulation. SARS-CoV-2 activity is at low levels with a declining trend. ILI activity has remained low. SARI activity is currently decreasing; however, the proportion of cases attributable to RSV continues to rise. In El Salvador, RSV activity remains high, coinciding with an increase in SARS-CoV-2 circulation. In Guatemala, RSV activity continues at moderate-high levels, with elevated ILI activity and epidemic levels of SARI cases, with most ILI cases testing positive for RSV and influenza, and most SARI cases testing positive for RSV. In Honduras, influenza activity continues to decrease, and SARS-CoV-2 activity is at high levels. SARI cases are currently decreasing below the epidemic threshold, with almost all positives related to influenza. In Nicaragua and Panama, following moderate activity levels in previous EWs, influenza positivity in both countries is currently at epidemic levels. In Panama, RSV activity is at moderate levels. Andean: Influenza activity remains stable at low levels. Over the past 4 EWs, the predominant influenza viruses have been influenza A, mainly A(H1N1)pdm09, and influenza B/Victoria. RSV activity remains at low levels. SARS-CoV-2 has shown a decline over the last 4 EWs, circulating at moderate levels, with elevated circulation in Bolivia. SARI activity continues to decline, with most cases associated with influenza and, to a lesser extent, RSV and SARS-CoV-2. ILI activity has shown a declining trend, with most cases associated with influenza. Brazil and Southern Cone: Influenza activity has decreased to low circulation levels. Over the past 4 EWs, the predominant influenza viruses have primarily been A(H1N1)pdm09, with concurrent circulation of influenza B/Victoria. RSV activity has declined in the last 4 EWs, reaching low circulation levels. SARS-CoV-2 activity has increased, although it remains low. SARI activity has continued to decline over the past 4 EWs, with most cases testing positive for RSV. ILI cases have shown a slight increase, with low positivity percentages for the monitored respiratory viruses. Argentina continues to present epidemic levels of influenza activity, with the majority of cases testing positive for influenza A(H1N1)pdm09. SARS-CoV-2 activity has increased to moderate levels, but ILI and SARI levels remain below the epidemic threshold. In Brazil, influenza activity is decreasing, while SARS-CoV-2 is on the rise, with SARI levels above the epidemic threshold. In Chile, ILI activity remains at moderate levels, showing a slight increase, with most cases related to influenza. SARI activity is currently decreasing below the epidemic threshold. In Paraguay, SARI activity has declined, reaching epidemic levels, with RSV being the primary cause among positive cases. In Uruguay, SARI activity has decreased over the past EWs, with most cases associated with RSV.

[RESUMEN SEMANAL]. Norteamérica: La actividad de influenza ha permanecido en niveles bajos. Durante las últimas 4 semanas epidemiológicas (SE) los virus influenza predominantes han sido influenza A(H1N1)pdm09, con circulación concurrente de influenza B/Victoria. La actividad del virus sincitial respiratorio (VSR) se ha mantenido en niveles bajos. La actividad del SARS-CoV-2 ha presentado un incremento en las últimas 4 SE y continúa circulando en niveles moderados. Los casos de enfermedad tipo influenza (ETI) e infección respiratoria aguda grave (IRAG) han mostrado un ligero incremento con un aumento en la proporción de casos positivos para SARS-CoV-2. En México se han detectado niveles moderados de circulación de influenza en las últimas SE, sin embrago la actividad de IRAG se mantiene baja, por encima del umbral epidémico, siendo la mayoría de los casos asociados a SARS-CoV-2. Caribe: La actividad de la influenza continúa mostrando una tendencia decreciente en las últimas 4 SE. Durante este periodo, los virus predominantes de la influenza han sido B/Victoria, con menor circulación de la influenza A, principalmente A(H1N1)pdm09. La actividad del VSR ha permanecido baja. La actividad del SARS-CoV-2 muestra una tendencia creciente con niveles intermedios de circulación. Los casos de ETI e IRAG han mostrado una tendencia decreciente en las últimas 4 SE. Centroamérica: La actividad de influenza continúa en descenso en las últimas 4 SE. Durante este periodo, los virus predominantes de influenza han sido influenza B/Victoria, con circulación concurrente de influenza A, principalmente A(H1N1)pdm09 y en menor medida de influenza A(H3N2). La actividad de VSR ha mostrado un incremnto en las últimas 4 SE, situándose en niveles medioaltos de circulación. La actividad de SARS-CoV-2 se encuentra en niveles bajos con una tendencia decreciente. La actividad de ETI se ha mantenido baja con la mayoría de los casos asociados a influenza. La actividad de IRAG se encuentra actualmente en descenso, sin embargo la proporción de casos atribuibles a VSR ha presentado un incremento. En El Salvador se ha observado un incremento en la actividad del VSR coincidente con un aumento en la circulación de SARS-CoV-2. En Honduras tras alcanzar niveles elevados en los porcentajes de positividad de influenza, en las 4 últimas SE se ha observado un descenso hasta niveles por debajo del umbral epidémico sin embargo la actividad del SARS-CoV-2 ha presentado un incremento en este periodo. Los casos de IRAG actualmente se encuentran en descenso siendo casi la totalidad de los positivos relacionados con influenza. En Guatemala la actividad del VSR continúa en ascenso con niveles moderados, y niveles de actividad de ETI e IRAG moderados, siendo los casos ETI positivos en su mayoría para influenza y los casos IRAG positivos para VSR. En Nicaragua y Panamá tras los niveles de actividad moderados alcanzados en SE previas, la positividad de influenza en ambos países se encuentra actualmente en niveles epidémicos. En Panmá la actividad de VSR ha presentado un incremento, situándose en niveles moderados. Andina: La actividad de la influenza se mantiene estable a niveles bajos. Durante las 4 últimas SE los virus influenza predominantes han sido influenza A, mayoritariamente A(H1N1)pdm09, con circulación en menor medida de influenza B/Victoria. La actividad del VSR, se mantiene en niveles bajos. El SARS-CoV-2 ha presentado un descenso en las 4 últimas SE, circulando en niveles moderados, con circulación elevada en Bolivia. La actividad de IRAG continúa en descenso con la mayoría de los casos asociados a influenza y en menor medida VSR y SARS-CoV-2. La actividad de ETI ha mostrado una tendencia decreciente con la mayoría de los casos asociados a influenza. Brasil y Cono Sur: La actividad de la influenza ha disminuido a niveles bajos de circulación. Durante las últimas 4 SE, los virus predominantes de la influenza han sido principalmente A(H1N1)pdm09, con circulación simultánea de influenza B/Victoria. La actividad del VSR ha presentado un descenso en las 4 últimas SE situándose en niveles bajos de circulación. La actividad del SARSCoV- 2 ha permanecido baja. Después de alcanzar un pico, tanto la actividad de IRAG como la de ETI han continuado en descenso en las últimas 4 SE, con la mayoría de los casos positivos para VSR en el caso de IRAG e influenza en los casos de ETI. Argentina continúa presentando niveles epidémicos en la actividad de influenza, siendo la mayoría de los casos detectados positivos para influenza A(H1N1)pdm09 con niveles de ETI e IRAG por debajo del umbral epidémico. En Brasil, la actividad de influenza se mantiene en descenso, mientras que el SARS-CoV-2 ha presentado un ligero incremento, con niveles de IRAG por encima del umbral epidémico y la mayorúa de los casos asociados a VSR y en menor medida, influenza. En Chile, la actividad de ETI se mantiene en niveles moderados con la mayoría de los casos relacionados con influenza. Tras alcanzar niveles moderados de actividad de IRAG, actualmente se encuentra en descenso en niveles epidémicos, siendo el VSR la causa más común entre los casos positivos. En Paraguay, la actividad de IRAG ha presentado un descenso situándose en niveles epidémicos, siendo el VSR la causa principal entre los casos positivos. En Uruguay la actividad de IRAG ha presentado un descenso en las últimas SE, siendo la mayoría de los casos asociados a VSR.

Contact patterns of older adults with and without frailty in the Netherlands during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, social distancing measures were imposed to protect the population from exposure, especially older adults and people with frailty, who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little was known about behaviour changes among older adults and people with frailty themselves. Our aim was to quantify how COVID-19 measures affected the contact behaviour of older adults and how this differed between older adults with and without frailty. METHODS: In 2021, a contact survey was carried out among people aged 70 years and older in the Netherlands. A random sample of persons per age group (70-74, 75-79, 80-84, 85-89, and 90 +) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves, including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week. RESULTS: In total, 720 community-dwelling older adults were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailty had significantly more contacts outside their household than participants with frailty. Especially for females, frailty was a more informative predictor of the number of contacts than age. During the survey period with stringent measures, participants with and without frailty had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of the number of contacts was largest for the eldest participants without frailty. As they interact mostly with adults of a similar high age who are likely frail, this reduction of the number of contacts indirectly protects older adults with frailty from SARS-CoV-2 exposure. CONCLUSIONS: The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailty. The reduction of contacts may have led to the direct protection of older adults in general but also to the indirect protection of older adults with frailty.

mRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States.

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

Predictors of the post-COVID condition following mild SARS-CoV-2 infection.

Whereas the nature of the post-COVID condition following mild acute COVID-19 is increasingly well described in the literature, knowledge of its risk factors, and whether it can be predicted, remains limited. This study, conducted in Norway, uses individual-level register data from 214,667 SARS-CoV-2 infected individuals covering a range of demographic, socioeconomic factors, as well as cause-specific healthcare utilization in the years prior to infection to assess the risk of post-COVID complaints ≥3 months after testing positive. We find that the risk of post-COVID was higher among individuals who prior to infection had been diagnosed with psychological (OR = 2.12, 95% CI 1.84-2.44), respiratory (OR = 2.03, 95% CI 1.78-2.32), or general and unspecified health problems (OR = 1.78, 95% CI 1.52-2.09). To assess the predictability of post-COVID after mild initial disease, we use machine learning methods and find that pre-infection characteristics, combined with information on the SARS-CoV-2 virus type and vaccine status, to a considerable extent (AUC = 0.79, 95% CI 0.75-0.81) could predict the occurrence of post-COVID complaints in our sample.

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

Evaluation of face shields used during aerosol generating procedures.

Transnasal flexible laryngoscopy is considered an aerosol generating procedure. A negative pressure face shield (NPFS) was developed to control aerosol from the patient during laryngoscopy. The purpose of this study was to determine the effectiveness of the NPFS at controlling virus aerosol compared to a standard disposable plastic face shield. The face shields were placed on a simulated patient coughing machine. MS2 bacteriophage was used as a surrogate for SARS-CoV-2 and was aerosolized using the coughing machine. The aerosolized virus was sampled on the inside and outside of the face shields. The virus aerosol concentration was not significantly different between the inside and outside of the traditional plastic face shield (p = 0.12). However, the particle concentrations across all particle sizes measured were significantly decreased outside the face shield. The virus and particle concentrations were significantly decreased (p < 0.01) outside the NPFS operating at a flow rate of 38.6 L per minute (LPM). When the NPFS was operated at 10 LPM, virus concentrations were not significantly different (p = 0.09) across the face shield. However, the number particle concentrations across all particle sizes measured were significantly different (p < 0.05).

Seroprevalence of SARS-CoV-2 anti-nucleocapsid total Ig, anti-RBD IgG antibodies, and infection in Thailand: a cross-sectional survey from October 2022 to January 2023.

Seroprevalence studies on SARS-CoV-2 are essential for estimating actual prevalence rates of infection and vaccination in communities. This study evaluated infection rates based on total anti-nucleocapsid immunoglobulin (N) and/or infection history. We determined the seroprevalence of anti-receptor binding domain (RBD) antibodies across age groups. A cross-sectional study was conducted in Chonburi province, Thailand, between October 2022 and January 2023. Participants included newborns to adults aged up to 80 years. All serum samples were tested for anti-N total Ig and anti-RBD IgG. The interviewer-administered questionnaires queried information on infection history and vaccination records. Of 1459 participants enrolled from the Chonburi population, ~ 72.4% were infected. The number of infections was higher in children aged < 5 years, with evidence of SARS-CoV-2 infection decreasing significantly with increasing age. There were no significant differences based on sex or occupation. Overall, ~ 97.4% of participants had an immune response against SARS-CoV-2. The anti-RBD IgG seroprevalence rate was lower in younger vaccinated individuals and was slightly increased to 100% seropositivity at ages > 60 years. Our findings will help predict the exact number of infections and the seroprevalence of SARS-CoV-2 in the Thai population. Furthermore, this information is essential for public health decision-making and the development of vaccination strategies.

Relatively preserved functional immune capacity with standard COVID-19 vaccine regimen in people living with HIV.

Introduction: People living with HIV (PLWH) are at a higher risk of severe disease with SARS-CoV-2 virus infection. COVID-19 vaccines are effective in most PLWH. However, suboptimal immune responses to the standard two-shot regimen are a concern, especially for those with moderate to severe immunodeficiency. An additional dose is recommended as part of the extended primary series in Taiwan. Herein, we study the efficacy of this additional shot in PLWH with mild immunodeficiency compared to that in healthy non-HIV people. Methods: In total, 72 PLWH that were asymptomatic or with mild immunodeficiency (CD4 counts ≥200/mm3) and suppressed virology, and 362 healthcare workers of our hospital were enrolled. None of the participants had a history of SARS-CoV-2 infection. They received mRNA-1273 and ChAdOx1 vaccines. Anti-SARS-CoV-2 neutralizing and anti-Spike IgG antibodies, and SARS-CoV-2-specific T cell responses were evaluated. Results: The standard two-shot regimen elicited lower responses in PLWH than the healthcare workers without HIV infection, although the difference was statistically insignificant. They had comparable levels of neutralizing and anti-Spike antibodies and comparable effector CD4+ and CD8+ T cell responses. The third shot boosted the SARS-CoV-2 immunity significantly more with better antibody responses and higher IFN-γ and IL-2 responses of the CD4+ and CD8+ T cells in PLWH compared to those without HIV. Upon in vitro stimulation with extracted Wuhan strain SARS-CoV-2 proteins, CD8+ T cells from PLWH after 3 shots had more durable effector responses than the non-HIV controls with extended time of stimulation. Conclusion: This subtle difference between PLWH and non-HIV people implied immune exhaustion with two shots in non-HIV people. Slightly compromised immunity in PLWH indeed preserved the functional capacity for further response to the third shot or natural infection.

Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants.

Background: Immune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear. Methods: This prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution. Results: The study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-α and IFN-ß), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-α, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-α, with cut-off value of 107 pg/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p<0.001), compared to those of IL-6, >17.9 pg/ml (OR=10.5; 95% CI, 2.9-46; p<0.001). Conclusions: This study demonstrated that serum IFN-α levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.

Factors influencing immunogenicity and safety of SARS-CoV-2 vaccine in liver transplantation recipients: a systematic review and meta-analysis.

Background: This review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use. Methods: Electronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used. Result: In total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ''positive leukopenia'' group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in <7years group and 83% (95% CI [0.76-0.90], P=0.000 I2 = 95.7%) in > 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000). Conclusion: The seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.