The Asymptomatic Proportion of SARS-CoV-2 Omicron Variant Infections in Households: A Systematic Review.

Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.

COVID-19-related temporary disability in healthcare workers in Spain during the four first pandemic waves.

Healthcare workers (HCW) have been the professional category most exposed to SARS-CoV-2. The pandemic's impact on HCW was analyzed in terms of COVID-19-related temporary disability (TD) between February 15th, 2020 and May 1st, 2021. TDs in HCW for COVID-19 infection or quarantine were described. TD quarantine/infection ratios and TDs per 100,000 affiliated HCW were compared with the cumulative incidence (CI) of COVID-19 cases notified to the National Network of Epidemiological Surveillance. TDs rates by economic activity and occupation were computed. A total of 429,127 TDs were recorded, 36,6% for infection. Three-quarters (76%) were women. The median TD quarantine/infection ratio was 2.5 (Interquartile range [IQR] 1.5-3.9). TDs rates in HCW were always above the CI except for the last two months of the fourth wave. Hospital activities accounted for 84% of TDs and showed the highest TD rate for infection (8,279/100,000). Nursing professionals and midwifery, Physicians, and Nursing assistants accounted for 26, 18 and 17 % of the conceded TD respectively, whereas the highest TDs rates were registered among Nursing assistants, Nursing professionals and Physicians: 7,426, 6,925 and 5,508/100,000, respectively. The results indicate the high impact of COVID-19 on HCW in Spain and it's inequalities. They also confirm that TDs represent a complementary source of information for epidemiological and public health surveillance and could provide an early warning of new emerging infections.

The Utility and Limitations of Universal Polymerase Chain Reaction Screening for SARS-CoV-2 During Hospital Admission.

OBJECTIVE: Universal polymerase chain reaction (PCR) screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admission is an effective approach to preventing coronavirus disease 2019 (COVID-19) outbreaks in medical facilities. However, false-positive test results due to a recent infection are a concern. We investigated the usefulness and limitations of universal PCR screening for SARS-CoV-2 on hospital admission in a real-world setting. METHODS: We retrospectively analyzed 1320 attempted hospital admissions for 775 patients at the Department of Respiratory Medicine, Kyushu University Hospital, between January 1, 2022, and May 2, 2023. RESULTS: Thirty-nine out of 1201 PCR tests (3.2%) yielded a positive result, with 22 of these results being considered false positives on the basis of a recent infection. We found that 39% of cases showed a positive PCR result between 31 and 60 days after the onset of COVID-19, although the threshold cycle (Ct) for target 1 (ORF1ab gene) of the Cobas SARS-CoV-2 test (Roche Diagnostics, Basel, Switzerland) was >30 in most instances. CONCLUSION: Hospital admission based on the results of PCR screening for SARS-CoV-2 should take into account not only PCR positivity but also the Ct value and recent COVID-19 history.

SARS-CoV-2 BA.4/5 infection triggers more cross-reactive FcγRIIIa signaling and neutralization than BA.1, in the context of hybrid immunity.

SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing and antibody-dependent cellular cytotoxic (ADCC) antibodies with variable cross-reactivity. Omicron BA.4/5 was approved for inclusion in bivalent vaccination boosters, and therefore the antigenic profile of antibodies elicited by this variant is critical to understand. Here, we investigate the ability of BA.4/5-elicited antibodies following the first documented (primary) infection (n = 13) or breakthrough infection after vaccination (n = 9) to mediate neutralization and FcγRIIIa signaling across multiple SARS-CoV-2 variants including XBB.1.5 and BQ.1. Using a pseudovirus neutralization assay and a FcγRIIIa crosslinking assay to measure ADCC potential, we show that unlike SARS-CoV-2 Omicron BA.1, BA.4/5 infection triggers highly cross-reactive functional antibodies. Cross-reactivity was observed both in the absence of prior vaccination and in breakthrough infections following vaccination. However, BQ.1 and XBB.1.5 neutralization and FcγRIIIa signaling were significantly compromised compared to other VOCs, regardless of prior vaccination status. BA.4/5 triggered FcγRIIIa signaling was significantly more resilient against VOCs (<10-fold decrease in magnitude) compared to neutralization (10- to 100-fold decrease). Overall, this study shows that BA.4/5 triggered antibodies are highly cross-reactive compared to those triggered by other variants. Although this is consistent with enhanced neutralization and FcγRIIIa signaling breadth of BA.4/5 vaccine boosters, the reduced activity against XBB.1.5 supports the need to update vaccines with XBB sublineage immunogens to provide adequate coverage of these highly antibody evasive variants. IMPORTANCE: The continued evolution of SARS-CoV-2 has resulted in a number of variants of concern. Of these, the Omicron sublineage is the most immune evasive. Within Omicron, the BA.4/5 sublineage drove the fifth wave of infection in South Africa prior to becoming the dominant variant globally. As a result this spike sequence was approved as part of a bivalent vaccine booster, and rolled out worldwide. We aimed to understand the cross-reactivity of neutralizing and Fc mediated cytotoxic functions elicited by BA.4/5 infection following infection or breakthrough infection. We find that, in contrast to BA.1 which triggered fairly strain-specific antibodies, BA.4/5 triggered antibodies that are highly cross-reactive for neutralization and antibody-dependent cellular cytotoxicity potential. Despite this cross-reactivity, these antibodies are compromised against highly resistant variants such as XBB.1.5 and BQ.1. This suggests that next-generation vaccines will require XBB sublineage immunogens in order to protect against these evasive variants.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission.

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring of its subvariants. Omicron subvariants are responsible for the vast majority of SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% of circulating strains as of January 2024. To better understand parameters involved in viral transmission, we characterized the functional properties of Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, BA.2.86 and JN.1. We tested their capacity to evade plasma-mediated recognition and neutralization, binding to angiotensin-converting enzyme 2 (ACE2), their susceptibility to cold inactivation, Spike processing, as well as the impact of temperature on Spike-ACE2 interaction. We found that compared to the early wild-type (D614G) strain, most Omicron subvariants' Spike glycoproteins evolved to escape recognition and neutralization by plasma from individuals who received a fifth dose of bivalent (BA.1 or BA.4/5) mRNA vaccine and improve ACE2 binding, particularly at low temperatures. Moreover, BA.2.86 had the best affinity for ACE2 at all temperatures tested. We found that Omicron subvariants' Spike processing is associated with their susceptibility to cold inactivation. Intriguingly, we found that Spike-ACE2 binding at low temperature was significantly associated with growth rates of Omicron subvariants in humans. Overall, we report that Spikes from newly emerged Omicron subvariants are relatively more stable and resistant to plasma-mediated neutralization, present improved affinity for ACE2 which is associated, particularly at low temperatures, with their growth rates.IMPORTANCEThe persistent evolution of SARS-CoV-2 gave rise to a wide range of variants harboring new mutations in their Spike glycoproteins. Several factors have been associated with viral transmission and fitness such as plasma-neutralization escape and ACE2 interaction. To better understand whether additional factors could be of importance in SARS-CoV-2 variants' transmission, we characterize the functional properties of Spike glycoproteins from several Omicron subvariants. We found that the Spike glycoprotein of Omicron subvariants presents an improved escape from plasma-mediated recognition and neutralization, Spike processing, and ACE2 binding which was further improved at low temperature. Intriguingly, Spike-ACE2 interaction at low temperature is strongly associated with viral growth rate, as such, low temperatures could represent another parameter affecting viral transmission.

Rapid Wane and Recovery of XBB Sublineage Neutralization After Sequential Omicron-based Vaccination in Solid Organ Transplant Recipients.

Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization.

A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

ABSTRACTSARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Prevalence and 3-month follow-up of cerebrovascular MRI markers in hospitalized COVID-19 patients: the CORONIS study.

PURPOSE: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months. METHODS: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders. RESULTS: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%). CONCLUSION: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization.

SARS-CoV-2-related peptides induce endothelial-to-mesenchymal transition in endothelial capillary cells derived from different body districts: focus on membrane (M) protein.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19, may lead to multiple organ dysfunctions and long-term complications. The induction of microvascular dysfunction is regarded as a main player in these pathological processes. To investigate the possible impact of SARS-CoV-2-induced endothelial-to-mesenchymal transition (EndMT) on fibrosis in "long-COVID" syndrome, we used primary cultures of human microvascular cells derived from the lungs, as the main infection target, compared to cells derived from different organs (dermis, heart, kidney, liver, brain) and to the HUVEC cell line. To mimic the virus action, we used mixed SARS-CoV-2 peptide fragments (PepTivator®) of spike (S), nucleocapsid (N), and membrane (M) proteins. TGFß2 and cytokine mix (IL-1ß, IL-6, TNFα) were used as positive controls. The percentage of cells positive to mesenchymal and endothelial markers was quantified by high content screening. We demonstrated that S+N+M mix induces irreversible EndMT in all analyzed endothelial cells via the TGFß pathway, as demonstrated by ApoA1 treatment. We then tested the contribution of single peptides in lung and brain cells, demonstrating that EndMT is triggered by M peptide. This was confirmed by transfection experiment, inducing the endogenous expression of the glycoprotein M in lung-derived cells. In conclusion, we demonstrated that SARS-CoV-2 peptides induce EndMT in microvascular endothelial cells from multiple body districts. The different peptides play different roles in the induction and maintenance of the virus-mediated effects, which are organ-specific. These results corroborate the hypothesis of the SARS-CoV-2-mediated microvascular damage underlying the multiple organ dysfunctions and the long-COVID syndrome.

Graphene Multiplexed Sensor for Point-of-Need Viral Wastewater-Based Epidemiology.

Wastewater-based epidemiology (WBE) can help mitigate the spread of respiratory infections through the early detection of viruses, pathogens, and other biomarkers in human waste. The need for sample collection, shipping, and testing facilities drives up the cost of WBE and hinders its use for rapid detection and isolation in environments with small populations and in low-resource settings. Given the ubiquitousness and regular outbreaks of respiratory syncytial virus, SARS-CoV-2, and various influenza strains, there is a rising need for a low-cost and easy-to-use biosensing platform to detect these viruses locally before outbreaks can occur and monitor their progression. To this end, we have developed an easy-to-use, cost-effective, multiplexed platform able to detect viral loads in wastewater with several orders of magnitude lower limit of detection than that of mass spectrometry. This is enabled by wafer-scale production and aptamers preattached with linker molecules, producing 44 chips at once. Each chip can simultaneously detect four target analytes using 20 transistors segregated into four sets of five for each analyte to allow for immediate statistical analysis. We show our platform's ability to rapidly detect three virus proteins (SARS-CoV-2, RSV, and Influenza A) and a population normalization molecule (caffeine) in wastewater. Going forward, turning these devices into hand-held systems would enable wastewater epidemiology in low-resource settings and be instrumental for rapid, local outbreak prevention.

SARS-CoV-2 and RSV bronchiolitis outcomes.

BACKGROUND: Severe acute respiratory syndrome related coronavirus (SARS-CoV-2) bronchiolitis has arisen with the SARS-CoV-2 pandemic. There is a paucity of literature on SARS-CoV-2 bronchiolitis. OBJECTIVE: The purpose of our paper was to review and compare outcomes in bronchiolitis due to severe acute respiratory syndrome related coronavirus 2 (SARS- CoV-2) and Respiratory Syncytial Virus (RSV). We also performed a subgroup analysis of two disrupted RSV seasons during the pandemic. METHODS: This was a retrospective study from a US TriNetX database from March 1, 2020-January 1, 2023. Propensity matching was utilized for confounders. RESULTS: There was a total of 3,592 patients (1,796 in each group) after propensity matching. There was an increased risk of oxygen saturation ≤95 % (RR=1.50 95 % CI 1.58-1.94, p = 0.002) and ICU admission (RR=1.44 95 % CI 1.06-1.94, p = 0.02) in those with SARS- CoV-2 but not for oxygen saturation ≤90 % (RR=1.03 95 %CI 0.75-1.42, p = 0.85) or intubation (RR=0.73 95 % CI 0.35-1.47, p = 0.37). There was a decreased risk of a patient with SARS- CoV-2 bronchiolitis being hospitalized (RR=0.65 95 % CI 0.57-0.74, p < 0.0001), respiratory rate ≥60 (RR=0.64 95 % CI 0.48-0.88, p < 0.001) or ≥70 (RR=0.64 95 % CI 0.43-0.96, p = 0.03) when compared to RSV bronchiolitis. Specifically examining SARS- CoV-2 versus RSV bronchiolitis during the delayed RSV seasons, during the first season both infections were not severe, but during the second RSV bronchiolitis season, patients infected with RSV had less risk of ICU admission compared to those infected with SARS- CoV-2. CONCLUSION: SARS- CoV-2 bronchiolitis patients appeared to have more severe outcomes since the risk of ICU admission was higher for these patients. Also, during the second delayed RSV season, SARS- CoV-2 bronchiolitis was more severe than RSV bronchiolitis.

Bioengineered self-assembled nanofibrils for high-affinity SARS-CoV-2 capture and neutralization.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spurred intense research efforts to develop new materials with antiviral activity. In this study, we genetically engineered amyloid-based nanofibrils for capturing and neutralizing SARS-CoV-2. Building upon the amyloid properties of a short Sup35 yeast prion sequence, we fused it to SARS-CoV-2 receptor-binding domain (RBD) capturing proteins, LCB1 and LCB3. By tuning the reaction conditions, we achieved the spontaneous self-assembly of the Sup35-LCB1 fusion protein into a highly homogeneous and well-dispersed amyloid-like fibrillar material. These nanofibrils exhibited high affinity for the SARS-CoV-2 RBD, effectively inhibiting its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor, the primary entry point for the virus into host cells. We further demonstrate that this functional nanomaterial entraps and neutralizes SARS-CoV-2 virus-like particles (VLPs), with a potency comparable to that of therapeutic antibodies. As a proof of concept, we successfully fabricated patterned surfaces that selectively capture SARS-CoV-2 RBD protein on wet environments. Collectively, these findings suggest that these protein-only nanofibrils hold promise as disinfecting coatings endowed with selective SARS-CoV-2 neutralizing properties to combat viral spread or in the development of sensitive viral sampling and diagnostic tools.

Single-molecule detection of SARS-CoV-2 N protein on multilayered plasmonic nanotraps with surface-enhanced Raman spectroscopy.

The spread of the SARS-CoV-2 virus has had an unprecedented impact, both by posing a serious risk to human health and by amplifying the burden on the global economy. The rapid identification of the SARS-CoV-2 virus has been crucial to preventing and controlling the spread of SARS-CoV-2 infections. In this study, we propose a multilayered plasmonic nanotrap (MPNT) device for the rapid identification of single particles of SARS-CoV-2 virus in ultra-high sensitivity by surface-enhanced Raman scattering (SERS). The MPNT device is composed of arrays of concentric cylindrical cavities with Ag/SiO2/Ag multilayers deposited on the top and at the bottom. By varying the diameter of the cylinders and the thickness of the multilayers, the resonant optical absorption and local electric field were optimized. The SERS enhancement factors of the proposed device are of the order of 108, which enable the rapid identification of SARS-CoV-2 N protein in concentrations as low as 1.25 × 10-15－12.5 × 10-15 g mL-1 within 1 min. The developed MPNT SERS device provides a label-free and rapid detection platform for SARS-CoV-2 virus. The general nature of the device makes it equally suitable to detect other infectious viruses.

Metabolomic Approach to Identify the Potential Metabolites from Alpinia malaccensis for Treating SARS-CoV-2 Infection.

The advent of the new coronavirus, leading to the SARS-CoV-2 pandemic, has presented a substantial worldwide health hazard since its inception in the latter part of 2019. The severity of the current pandemic is exacerbated by the occurrence of re-infection or co-infection with SARS-CoV-2. Hence, comprehending the molecular process underlying the pathophysiology of sepsis and discerning possible molecular targets for therapeutic intervention holds significant importance. For the first time, 31 metabolites were tentatively identified by GC-MS analysis from Alpinia malaccensis. On the other hand, five phenolic compounds were identified and quantified from the plant in HPLC-DAD analysis, including (-) epicatechin, rutin hydrate, rosmarinic acid, quercetin, and kaempferol. Nine GC-MS and five HPLC-identified metabolites had shown interactions with 45 and 30 COVID-19-associated human proteins, respectively. Among the proteins, PARP1, FN1, PRKCA, EGFR, ALDH2, AKR1C3, AHR, and IKBKB have been found as potential therapeutic targets to mitigate SARS-CoV-2 infection. KEGG pathway analysis also showed a strong association of FN1, EGFR, and IKBKB genes with SARS-CoV-2 viral replication and cytokine overexpression due to viral infection. Protein-protein interaction (PPI) analysis also showed that TP53, MMP9, FN1, EGFR, and NOS2 proteins are highly related to the genes involved in COVID-19 comorbidity. These proteins showed interaction with the plant phytoconstituents as well. As the study offers a robust network-based procedure for identifying biomolecules relevant to COVID-19 disease, A. malaccensis could be a good source of effective therapeutic agents against COVID-19 and related viral diseases.

Differences in virus and immune dynamics for SARS-CoV-2 Delta and Omicron infections by age and vaccination histories.

Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

Environmental and geographical factors influencing the spread of SARS-CoV-2 over 2 years: a fine-scale spatiotemporal analysis.

Introduction: Since its emergence in late 2019, the SARS-CoV-2 virus has led to a global health crisis, affecting millions and reshaping societies and economies worldwide. Investigating the determinants of SARS-CoV-2 diffusion and their spatiotemporal dynamics at high spatial resolution is critical for public health and policymaking. Methods: This study analyses 194,682 georeferenced SARS-CoV-2 RT-PCR tests from March 2020 and April 2022 in the canton of Vaud, Switzerland. We characterized five distinct pandemic periods using metrics of spatial and temporal clustering like inverse Shannon entropy, the Hoover index, Lloyd's index of mean crowding, and the modified space-time DBSCAN algorithm. We assessed the demographic, socioeconomic, and environmental factors contributing to cluster persistence during each period using eXtreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP), to consider non-linear and spatial effects. Results: Our findings reveal important variations in the spatial and temporal clustering of cases. Notably, areas with flatter epidemics had higher total attack rate. Air pollution emerged as a factor showing a consistent positive association with higher cluster persistence, substantiated by both immission models and, to a lesser extent, tropospheric NO2 estimations. Factors including population density, testing rates, and geographical coordinates, also showed important positive associations with higher cluster persistence. The socioeconomic index showed no significant contribution to cluster persistence, suggesting its limited role in the observed dynamics, which warrants further research. Discussion: Overall, the determinants of cluster persistence remained across the study periods. These findings highlight the need for effective air quality management strategies to mitigate air pollution's adverse impacts on public health, particularly in the context of respiratory viral diseases like COVID-19.

Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study.

There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.

Identification of Differentially Expressed Genes and Protein-Protein Interaction in Patients With COVID-19 and Diabetes Peripheral Neuropathy: A Bioinformatics and System Biology Approach.

The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact globally, resulting in a higher death toll and persistent health issues for survivors, particularly those with pre-existing medical conditions. Numerous studies have demonstrated a strong correlation between catastrophic COVID-19 results and diabetes. To gain deeper insights, we analysed the transcriptome dataset from COVID-19 and diabetic peripheral neuropathic patients. Using the R programming language, differentially expressed genes (DEGs) were identified and classified based on up and down regulations. The overlaps of DEGs were then explored between these groups. Functional annotation of those common DEGs was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Bio-Planet, Reactome, and Wiki pathways. A protein-protein interaction (PPI) network was created with bioinformatics tools to understand molecular interactions. Through topological analysis of the PPI network, we determined hub gene modules and explored gene regulatory networks (GRN). Furthermore, the study extended to suggesting potential drug molecules for the identified mutual DEG based on the comprehensive analysis. These approaches may contribute to understanding the molecular intricacies of COVID-19 in diabetic peripheral neuropathy patients through insights into potential therapeutic interventions.