Feasibility and Effectiveness of Vaccines for COVID-19: An Umbrella Review.

Introduction: In January 2020, WHO declared the 2019 Coronavirus Disease (COVID-19) a pandemic. Though COVID-19 vaccines are recommended, ongoing surveillance is crucial due to potential unforeseen events. Evaluation of long-term effectiveness and safety and addressing emerging variants are vital. This study integrates systematic reviews to assess COVID-19 vaccine efficacy, immunogenicity, and safety comprehensively. Methods: This study was an umbrella review study on the feasibility and effectiveness of vaccines for COVID-19. We conducted a comprehensive search in PubMed, Web of Sciences, and Scopus, using MeSH terms and keywords related to COVID-19 vaccines. Inclusion criteria comprised peer-reviewed systematic reviews and meta-analyses in English, focusing on feasibility and effectiveness. Exclusion criteria targeted non-systematic reviews exclusively on vaccine safety and duplicates. Two independent reviewers screened and resolved discrepancies. Data extraction included key details. Methodological quality was assessed using the ROBIS tool. Data synthesis involves narrative and, if applicable, quantitative synthesis (meta-analysis). Reporting followed PRISMA guidelines. Results: A total of 32 systematic reviews were included in the study, of which 20 also conducted a meta-analysis. The studies investigated in the included reviews ranged from 7 to 74. The included articles were conducted in various countries around the globe. The findings indicated that COVID-19 vaccines are generally safe and effective for individuals with various medical conditions. The overall risk of bias for the included studies was assessed as low risk. Conclusion: The study outcomes indicated that mRNA vaccines exhibit a higher incidence of adverse events but demonstrate greater efficacy. Conversely, inactivated and protein subunit vaccines are safer but exhibit lower efficiency. Moreover, the vaccine is considered safe for individuals with specific conditions such as inflammatory bowel disease, solid organ transplant recipients, children, pregnant individuals, and those with hematologic problems. Ultimately, the acceptance of the COVID-19 vaccine among individuals is influenced by various factors, including geographic, socioeconomic, and pandemic-related considerations.

Approaching Pharmacological Space: Events and Components.

The pharmacological space comprises all the dynamic events that determine the bioactivity (and/or the metabolism and toxicity) of a given ligand. The pharmacological space accounts for the structural flexibility and property variability of the two interacting molecules as well as for the mutual adaptability characterizing their molecular recognition process. The dynamic behavior of all these events can be described by a set of possible states (e.g., conformations, binding modes, isomeric forms) that the simulated systems can assume. For each monitored state, a set of state-dependent ligand- and structure-based descriptors can be calculated. Instead of considering only the most probable state (as routinely done), the pharmacological space proposes to consider all the monitored states. For each state-dependent descriptor, the corresponding space can be evaluated by calculating various dynamic parameters such as mean and range values.The reviewed examples emphasize that the pharmacological space can find fruitful applications in structure-based virtual screening as well as in toxicity prediction. In detail, in all reported examples, the inclusion of the pharmacological space parameters enhances the resulting performances. Beneficial effects are obtained by combining both different binding modes to account for ligand mobility and different target structures to account for protein flexibility/adaptability.The proposed computational workflow that combines docking simulations and rescoring analyses to enrich the arsenal of docking-based descriptors revealed a general applicability regardless of the considered target and utilized docking engine. Finally, the EFO approach that generates consensus models by linearly combining various descriptors yielded highly performing models in all discussed virtual screening campaigns.

Choroiditis following severe acute respiratory syndrome coronavirus 2 infection in unvaccinated identical twins

ABSTRACT Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.

Exploring the treatment of SARS-CoV-2 with modified vesicular stomatitis virus.

SARS-CoV-2 caused a global pandemic and is now an endemic virus that will require continued antiviral and vaccine development. A possible new treatment modality was recently suggested that would use vesicular stomatitis virus (VSV) modified to express the ACE2 receptor. Since the modified VSV expresses the cell surface receptor that is used by the SARS-CoV-2 spike protein, the thought is that SARS-CoV-2 virions would bind to the modified VSV and thus be neutralized. Additionally, since SARS-CoV-2 infected cells also express the spike protein, the modified VSV could potentially infect these cells, allowing for its own replication, but also potentially interfering with replication of SARS-CoV-2. This idea has not yet been tested experimentally, but we can investigate the feasibility of this possible treatment theoretically. In this manuscript, we develop a mathematical model of this suggested treatment and explore conditions under which it might be effective. We find that treatment with modified VSV does little to change the SARS-CoV-2 time course except when the treatment is applied at the onset of the SARS-CoV-2 infection at very high doses. In this case, VSV reduces the peak SARS-CoV-2 viral load, but lengthens the duration of the SARS-CoV-2 infection. Thus, we find that modified VSV treatment is unlikely to be effective largely because it does not prevent infection of cells by SARS-CoV-2.

LAMP-CRISPR/Cas12a-based impedimetric biosensor powered by Fe3O4@Au-(S-polyA-S)-Au for detection of SARS-CoV-2.

A low-cost, lab-made polytetrafluoroethylene micro-cell, equipped with three electrodes, wasd eveloped for the impedimetric detection of SARS-CoV-2. The gold working electrode was modified with a double-ended thiolated poly-adenine probe, which was conjugated with magnetic Fe3O4@Au nanoparticles (Fe3O4@Au-(S-polyA-S)-Au). After the loop-mediated isothermal amplification (LAMP) of viral RNA, the single-guide RNA (sgRNA), specifically bound to the SARS-CoV-2 target sequence, activates Cas12a. Cas12a then cleaved the immobilized probe. As a result, the magnetic Fe3O4@Au nanoparticles were released and adsorbed onto the gold electrode surface, using an external magnet. This process increased the physical surface area of the gold electrode, facilitating redox ion ([FeIII/II(CN)6]3-/4-) electron transfer. The decrease in the charge transfer resistance was utilized for SARS-CoV-2 detection. Our LAMP-CRISPR/Cas12a-based impedimetric biosensor, powered by Fe3O4@Au-(S-polyA-S)-Au, demonstrated impressive capabilities, including a remarkable detection limit of 0.8 aM (0.48 copies/µL) and a linear range of 0.01 to 36.06 fM.

Shift in Demographic Involvement and Clinical Characteristics of COVID-19 From Wild-Type SARS-CoV-2 to the Delta Variant in the Indian Population: In Silico Analysis.

BACKGROUND: The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. OBJECTIVE: We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). METHODS: A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. RESULTS: With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. CONCLUSIONS: The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

Influenza-Like Illness in Lesotho From July 2020 to July 2021: Population-Based Participatory Surveillance Results.

Background: Participatory surveillance involves at-risk populations reporting their symptoms using technology. In Lesotho, a landlocked country of 2 million people in Southern Africa, laboratory and case-based COVID-19 surveillance systems were complemented by a participatory surveillance system called "LeCellPHIA" (Lesotho Cell Phone Population-Based HIV Impact Assessment Survey). Objective: This report describes the person, place, and time characteristics of influenza-like illness (ILI) in Lesotho from July 15, 2020, to July 15, 2021, and reports the risk ratio of ILI by key demographic variables. Methods: LeCellPHIA employed interviewers to call participants weekly to inquire about ILI. The average weekly incidence rate for the year-long period was created using a Quasi-Poisson model, which accounted for overdispersion. To identify factors associated with an increased risk of ILI, we conducted a weekly data analysis by fitting a multilevel Poisson regression model, which accounted for 3 levels of clustering. Results: The overall response rate for the year of data collection was 75%, which resulted in 122,985 weekly reports from 1776 participants. ILI trends from LeCellPHIA mirrored COVID-19 testing data trends, with an epidemic peak in mid to late January 2021. Overall, any ILI symptoms (eg, fever, dry cough, and shortness of breath) were reported at an average weekly rate of 879 per 100,000 (95% CI 782-988) persons at risk. Compared to persons in the youngest age group (15-19 years), all older age groups had an elevated risk of ILI, with the highest risk of ILI in the oldest age group (≥60 years; risk ratio 2.6, 95% CI 1.7-3.8). Weekly data were shared in near real time with the National COVID-19 Secretariat and other stakeholders to monitor ILI trends, identify and respond to increases in reports of ILI, and inform policies and practices designed to reduce COVID-19 transmission in Lesotho. Conclusions: LeCellPHIA, an innovative and cost-effective system, could be replicated in countries where cell phone ownership is high but internet use is not yet high enough for a web- or app-based surveilance system.

Risk for Facial Palsy after COVID-19 Vaccination, South Korea, 2021-2022.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

An integrative analysis of SARS-CoV 2 during the first and second waves of COVID-19 in Salta, Argentina.

Wastewater surveillance has been extensively applied to provide information about SARS-CoV-2 circulation in the community. However, its applicability is limited in regions lacking adequate sewerage infrastructure, without wastewater treatment plants (WWTP) or with insufficient coverage. During the COVID-19 pandemic, from July 2020 to September 2021, comprehensive epidemiological data encompassing positive, recovered, and deceased cases were collected alongside precipitation records. Additionally, wastewater samples from 13 main sewersheds and river water from two points (up- and downstream the main WWTP), in the city of Salta, were gathered. A total of 452 water samples were analyzed for quantitative detection of SARS-CoV-2 using reverse transcription real-time PCR. Across the 62-week study period, two distinct waves of COVID-19 were identified. The dynamics of deceased cases showed peaks 10 and 28 days after the peaks of positive cases in the first and second waves, respectively. Downstream river water exhibited higher fecal contamination than the upstream samples, evincing the impact of the WWTP discharges. Viral concentration in river waters mirrored those from wastewater, reflecting the progression of cases. Despite the lower reported number of cases during the first wave in comparison to the second (5420 vs. 8516 cases at the respective peaks), higher viral concentrations were detected in water samples (1.97 × 107 vs. 2.36 × 106 gc/L, respectively), suggesting underreporting during the first wave, and highlighting the positive effect of vaccination during the second. To the best of our knowledge, this is the first study that simultaneously and systematically analyzed surface water and wastewater over a prolonged period, the effect of precipitations were considered for the variations in the concentrations, and the findings compared with epidemiological information. Environmental surveillance was demonstrated to be a great tool to obtain valuable information about the circulation patterns of SARS-CoV-2, especially under resource constraints to massively test the population, thus, underreporting cases. Furthermore, the methodology employed herein can be easily expanded to the community-level surveillance of other pathogens excreted in urine and feces, encompassing viruses, bacteria, and protozoa.

The Outcome of SARS-CoV-2 Infection in Patients with Lymphoma and the Risk Factors for the Development of Pneumonia.

BACKGROUND: Although patients with lymphoma appear particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the clinical evolution of coronavirus disease 2019 (COVID-19) in a patient with lymphoid malignancies has been under-represented, especially in relation to chemo-, chemo-immunotherapy. MATERIALS AND METHODS: Among adult patients with lymphoma receiving treatment in a specialized lymphoma center at a 500-bed, university-affiliated hospital, we retrospectively reviewed the medical records of patients diagnosed with SARS-CoV-2 infection from January 2020 to April 2022. RESULTS: A total of 117 patients with a median age of 53 years were included. One hundred twelves (95.7%) were non-Hodgkin lymphoma. Eighty-six patients (73.5%) were on active chemotherapy and 9 were post stem cell transplant state. Sixty-one patients had more than one comorbidity and 29 had hypogammaglobulinemia. Thirty-four patients (29.1%) had never received a COVID-19 vaccine. During a median follow-up of 134 days, COVID-19 pneumonia developed in 37 patients (31.6%). Excluding three patients who died before the 30 days, 31 out of 34 patients had ongoing symptomatic COVID-19. Eleven patients (9.4%) had post COVID-19 lung condition that persisted 90 days after COVID-19 diagnosis. Overall mortality was 10.3% (12 of 117), which was higher in patients with pneumonia. In multivariate analyses, age 65 years or older, follicular lymphoma, receiving rituximab maintenance therapy, and lack of vaccination were significantly associated with the development of COVID-19 pneumonia. CONCLUSION: Patients with lymphoma are at high risk for developing pneumonia after SARS-CoV-2 infection and suffer from prolonged symptoms. More aggressive vaccination and protective measures for patients with lymphoma who have impaired humoral response related to rituximab maintenance therapy and hypogammaglobulinemia are needed.

Predictors of seropositivity to SARS-CoV-2 among employees at a large urban medical center.

BACKGROUND: Before SARS-CoV-2 vaccination availability, medical center employees were at high risk of COVID-19. However, risk factors for SARS-CoV-2 infection in medical center employees, both healthcare and non-healthcare workers, are poorly understood. METHODS: From September-December 2020, free IgG antibody testing was offered to all employees at a large urban medical center. Participants were asked to complete a questionnaire on work and non-work related risk factors for COVID-19 infection. RESULTS: SARS-CoV-2 seropositivity was found in 4.7%. Seropositivity was associated with close contact with COVID-19 cases with or without the use of adequate personal protective equipment (PPE), (OR 3.1 [95% CI 1.4-6.9] and OR 4.7 [95% CI 2.0-11.0] respectively), never wearing a mask outside of work (OR 10.1 [95% CI 1.9-57]), and Native Hawaiian/Pacific Islander race (OR 6.3 95% CI (1.6-25)]. CONCLUSIONS: Among workers in a large urban medical center, SARS-CoV-2 seropositivity was associated with work-related COVID-19 close contacts and low mask use outside of work, suggesting that non-workplace close contacts are also relevant routes of COVID-19 spread among healthcare workers.

Socioeconomic factors and COVID-19 mortality in immune-mediated rheumatic diseases patients: regional analysis from Argentina, Mexico and Brazil.

BACKGROUND: SARS-CoV-2 infection has become a major international issue, not only from a medical point of view, but also social, economic and political. Most of the available information comes from the United States, Europe, and China, where the population and the socioeconomic status are very different from Latin American countries. This study evaluates the effect of regional socioeconomic characteristics on mortality due SARS-CoV-2 infection in patients with immune-mediated rheumatic diseases (IMRD) from Argentina, Mexico and Brazil. METHODS: Data from three national registries, SAR-COVID (Argentina), CMR-COVID (Mexico) and ReumaCoV-Brasil (Brazil), were combined. Adult IMRD patients with SARS-CoV-2 infection were recruited. National data for each province/state, including population density, number of physicians per inhabitant, income, unemployment, GINI index, Municipal Human Development Index (MHDI), stringency index, vaccination rate and most frequent viral strains per period were assessed as risk factors for mortality due to COVID-19. RESULTS: A total of 4744 patients were included, 2534 (53.4%) from SAR-COVID, 1166 (24.6%) from CMRCOVID and 1044 (22.0%) from ReumaCoV-Brasil. Mortality due to COVID-19 was 5.4%. In the multivariable analysis, higher number of physicians per 1000 inhabitants and being infected during the vaccination period of each country were associated with lower mortality. After adjustment for socioeconomic factors, there was no association with country of residence and mortality. CONCLUSION: These findings corroborate the complex interplay between socioeconomic factors, rheumatic disease activity, and regional disparities as determinants of death due to COVID-19 in Argentina, Brazil and Mexico. Thus, this research provides valuable insights for guiding public health policies and clinical practice in the ongoing fight against the COVID-19 pandemic.

Corrigendum: Risk of SARS-CoV-2 infection among people living with HIV in Wuhan, China.

[This corrects the article DOI: 10.3389/fpubh.2022.833783.].

COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type.

BACKGROUND: COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post-COVID-19 are not known. METHODS: Data from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score-matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (>1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components. RESULTS: The risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94-2.25]; P<0.0005) and to a greater extent in cases hospitalized for COVID-19 (HR, 3.85 [95% CI, 3.51-4.24]; P<0.0005). Hospitalization for COVID-19 represented a coronary artery disease risk equivalent since incident MACE risk among cases without history of cardiovascular disease was even higher than that observed in patients with cardiovascular disease without COVID-19 (HR, 1.21 [95% CI, 1.08-1.37]; P<0.005). A significant genetic interaction was observed between the ABO locus and hospitalization for COVID-19 (Pinteraction=0.01), with risk of thrombotic events being increased in subjects with non-O blood types (HR, 1.65 [95% CI, 1.29-2.09]; P=4.8×10-5) to a greater extent than subjects with blood type O (HR, 0.96 [95% CI, 0.66-1.39]; P=0.82). CONCLUSIONS: Hospitalization for COVID-19 represents a coronary artery disease risk equivalent, with post-acute myocardial infarction and stroke risk particularly heightened in non-O blood types. These results may have important clinical implications and represent, to our knowledge, one of the first examples of a gene-pathogen exposure interaction for thrombotic events.

Early impact of treatment modifications adopted for acute lymphoblastic leukemia during SARS-CoV-2 pandemic; a single center experience and lessons for LMICs.

Treatment modifications adopted during pandemic aimed at reducing infection, myelosuppression, and optimizing hospital resources. This study evaluated outcomes for pediatric patients with ALL who had treatment modifications during pandemic compared to historical cohorts at the National Cancer Institute, Cairo University, Egypt. Bi-directional cohort study included 378 patients. Treatment modifications included omission of specific drugs or adjusting chemotherapy schedules to 6-mercaptopurine/methotrexate. Median follow-up were 45.1 and 43.2 months, for cohorts (A) and (B), respectively. The three-year overall survival were 84.9% and 87.5% (p = .48) and three-year relapse free survival were 82.8% and 86.5% (p = .11) for cohorts (A) and (B), respectively. Infection-related mortality was 11% and 4.4% for cohorts (A) and (B), respectively (p = .03). Treatment modifications adopted during the pandemic did not adversely affect the outcome of patients with ALL and notably reduced infection-related deaths. Longer follow-up is warranted to validate these findings.

Exploring the causes of variability in quality of oropharyngeal swab sampling for SARS-CoV-2 nucleic acid testing and proposed improvement measures: a multicenter, double-blind study.

Although coronavirus disease 2019 (COVID-19) has not been considered a public health emergency of international concern since last year, intermittent regional impacts still persist, and accurate testing remains crucial. Ribonuclease P protein subunit P30 (RPP30) RNA, known for its broad and stable expression in tissue cells, was used to evaluate samples from 10 hospitals with over 3,000 negative nucleic acid tests. The results revealed that the overall pass rate for the collected samples was consistently low and exhibited significant heterogeneity. After reassessing the evaluative effectiveness of RPP30 RNA Ct values from the samples of 132 positive individuals under quarantine observation, it was used to identify factors affecting sampling quality. These factors included different stages ranging from sample collection to PCR processing, various characteristics of both samplers and individuals being sampled, as well as sampling season and location. The results indicated that post-sampling handling had minimal impact, winter and fever clinic samples showed higher quality, whereas children's samples had lower quality. The key finding was that the characteristics of samplers were closely related to sampling quality, emphasizing the role of subjectivity. Quality control warnings led to substantial improvements, confirming this finding. Consequently, although there are various factors during the testing process, the most critical aspect is to improve, supervise, and maintain standardized practices among sampling staff.IMPORTANCEThis study further confirmed the reliability of internal references (IRs) in assessing sample quality, and utilized a large sample IR data to comprehensively and multidimensionally identify significant interference factors in nucleic acid test results. By further reminding and intervening in the subjective practices of specimen collectors, good results could be achieved.

Correlation of patient symptoms with SARS-CoV-2 Omicron variant viral loads in nasopharyngeal and saliva samples and their influence on the performance of rapid antigen testing.

Evaluating SARS-CoV-2 viral loads in nasopharyngeal (NP) and saliva samples, factors affecting viral loads, and the performance of rapid antigen testing (RAT) have not been comprehensively conducted during SARS-CoV-2 Omicron epidemic. This prospective study included outpatients enrolled during Omicron variant period in Japan. Paired NP swab and saliva samples were collected to measure viral loads by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between viral loads and clinical symptoms was examined. The performance of an immunochromatography-based RAT kit was also assessed. A total of 153 patients tested within 3 days of symptom onset were included. The mean viral load was 5.60 log10 copies/test and 3.65 log10 copies/test in NP and saliva samples, respectively, resulting in a significant difference (P < 0.0001). Fever over 37°C (axillary temperature) and total number of symptoms other than fever were identified as independent factors positively correlated with the viral loads in both NP and saliva samples. RAT sensitivity using NP and saliva samples was 92% and 68%, respectively, using positive RT-qPCR results as the reference. The sensitivity of RAT using NP and saliva samples was significantly higher in patients with fever ≥37°C and/or at least one symptom than in those with fever <37°C and/or no symptoms (97% vs 83% in NP swabs; 80% vs 50% in saliva). Distinct symptoms, including fever ≥37°C, may reflect high Omicron variant viral loads. Rapid antigen testing, not only using nasopharyngeal swabs but also using saliva, would be useful for COVID-19 diagnosis as point-of-care testing, particularly for symptomatic patients. IMPORTANCE: We examined nasopharyngeal and salivary viral loads using samples collected from outpatients with SARS-CoV-2 infection during the Omicron epidemic in Japan and explored the outpatient factors correlated with viral loads. In addition, we evaluated the performance of an authorized rapid antigen testing (RAT) kit using nasopharyngeal and saliva samples with RT-PCR testing as the reference. Intriguingly, a correlation between fever and other symptoms and SARS-CoV-2 viral loads in nasopharyngeal and saliva samples was observed based on one COVID-19 outpatient visit. RAT sensitivity was influenced by viral loads. Nevertheless, nasopharyngeal RAT is considered useful for SARS-CoV-2 point-of-care diagnosis. In patients with distinct symptoms, including high-grade fever, salivary RAT could be a practical diagnostic tool because of the higher estimated viral loads. After the Omicron epidemic, outpatients with mild COVID-19 have become the main focus of diagnosis and treatment. Our study provides valuable information regarding the point-of-care diagnosis of these patients.

Epidemiological comparison of emergency department presentations with seasonal influenza or COVID-19 and an outcome of intensive care admission or death: a population-based records linkage study in New South Wales, Australia.

BACKGROUND: COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection. METHODS: De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death). RESULTS: Influenza infection was notified in 2,335 and COVID-19 in 5,053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period. CONCLUSIONS: The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.

Interplay of calcium, Vitamin D, and parathormone in the milieu of infections and immunity: reassessed in the context of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized for inducing severe respiratory symptoms like cough, and shortness of breathing. Although symptom severity varies, some individuals remain asymptomatic. This virus has sparked a global pandemic, imposing a substantial rate of mortality or morbidity, with extended periods of illness reported. People with underlying medical issues and the elderly are more likely to experience adverse results. The virus's frequent mutations pose challenges for medical professionals, necessitating adaptable therapeutic and preventive strategies. Vitamin D, a versatile regulatory molecule, not only influences physiological processes such as serum calcium regulation but also exhibits immunomodulatory functions. Calcium ions play a crucial role as secondary signal transduction molecules, impacting diverse cellular functions and maintaining homeostasis through ion channel regulation. Parathormone, another key regulator of serum calcium, often acts antagonistically to vitamin D. This review delves into the interplay of vitamin D, calcium, and parathormone, exploring their possible influence on the progression of COVID-19. The intricate signaling involving these elements contributes to adverse prognosis, emphasizing the need for comprehensive understanding. Monitoring and controlling these physiological factors and associated pathways have shown the potential to alter disease outcomes, underscoring the importance of a holistic approach.

Integrated analyses of the transmission history of SARS-CoV-2 and its association with molecular evolution of the virus underlining the pandemic outbreaks in Italy, 2019-2023.

BACKGROUND: Italy was significantly affected by the COVID-19 pandemic, experiencing multiple waves of infection following the sequential emergence of new variants. Understanding the transmission patterns and evolution of SARS-CoV-2 is vital for future preparedness. METHODS: We conducted an analysis of viral genome sequences, integrating epidemiological and phylodynamic approaches, to characterize how SARS-CoV-2 variants have spread within the country. RESULTS: Our findings indicate bidirectional international transmission, with Italy transitioning between importing and exporting the virus. Italy experienced four distinct epidemic waves, each associated with a significant reduction in fatalities from 2021 to 2023. These waves were primarily driven by the emergence of VOCs such as Alpha, Delta, and Omicron, which were reflected in observed transmission dynamics and effectiveness of public health measures. CONCLUSIONS: The changing patterns of viral spread and variant prevalence throughout Italy's pandemic response underscore the continued importance of flexible public health strategies and genomic surveillance, both of which are crucial for tracking the evolution of variants and adapting control measures effectively to ensure preparedness for future outbreaks.