Covid19-Sources

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A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers
A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers
Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP™) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers ([NCT05358873][1]). COVITRAP™ exhibited broadly potent 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, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP™ or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP™ was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP™ were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP™ application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP™ was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP™ can be considered an integral instrument for COVID-19 prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05358873 ### Funding Statement This study was sponsored by HIBIOCY Co., Ltd., and funded by the Program Management Unit Competitiveness (PMU-C) [Grant No. C10F650051], Ministry of Higher Education, Science, Research and Innovation, Thailand. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the Department of Medical Services, Ministry of Public Health, Thailand gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05358873&atom=%2Fmedrxiv%2Fearly%2F2022%2F10%2F05%2F2022.10.04.22280574.atom
·medrxiv.org·
A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers
IgG4 Antibodies Induced by mRNA Vaccines Generate Immune Tolerance to SARS-CoV-2’spike Protein by Suppressing the Immune System
IgG4 Antibodies Induced by mRNA Vaccines Generate Immune Tolerance to SARS-CoV-2’spike Protein by Suppressing the Immune System
Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.
·preprints.org·
IgG4 Antibodies Induced by mRNA Vaccines Generate Immune Tolerance to SARS-CoV-2’spike Protein by Suppressing the Immune System
Clinical case definition of post-COVID-19 condition in children: a good start, but improvements are needed
Clinical case definition of post-COVID-19 condition in children: a good start, but improvements are needed
On Feb 16, 2023, WHO issued a new clinical case definition for post-COVID-19 condition, also known as long COVID, in children and adolescents. It stated that the condition occurs in “individuals with a history of confirmed or probable SARS-CoV-2 infection, when experiencing symptoms lasting at least 2 months which initially occurred within 3 months of acute COVID-19”. Fatigue, altered smell or anosmia, and anxiety were picked out as being the symptoms most strongly associated with post-COVID-19 condition in children and adolescents.
·thelancet.com·
Clinical case definition of post-COVID-19 condition in children: a good start, but improvements are needed
Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients
Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla. Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.” In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.
·frontiersin.org·
Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients
Current understanding of T cell immunity against SARS-CoV-2 - Inflammation and Regeneration
Current understanding of T cell immunity against SARS-CoV-2 - Inflammation and Regeneration
As an important part of adaptive immunity, T cells are indispensable in the defense against pathogens including viruses. SARS-CoV-2 is a new human coronavirus that occurred at the end of 2019 and has caused the COVID-19 pandemic. Nevertheless, most of the infected patients recovered without any antiviral therapies, suggesting an effective immunity developed in the bodies. T cell immunity responds upon SARS-CoV-2 infection or vaccination and plays crucial roles in eliminating the viruses and generating T cell memory. Specifically, a subpopulation of CD4+ T cells could support the production of anti-SARS-CoV-2 antibodies, and cytotoxic CD8+ T cells are also protective against the infection. SARS-CoV-2–recognizing T cells could be detected in SARS-CoV-2–unexposed donors, but the role of these cross-reactive T cells is still in debate. T cell responses could be diverse across individuals, mainly due to the polymorphism of HLAs. Thus, compared to antibodies, T cell responses are generally less affected by the mutations of SARS-CoV-2 variants. Up to now, a huge number of studies on SARS-CoV-2–responsive T cells have been published. In this review, we introduced some major findings addressing the questions in the main aspects about T cell responses elicited by SARS-CoV-2, to summarize the current understanding of COVID-19.
·inflammregen.biomedcentral.com·
Current understanding of T cell immunity against SARS-CoV-2 - Inflammation and Regeneration
Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November–December 2022
Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November–December 2022
Nature Medicine - With the lifting of the zero-COVID policy and requirements governing reporting case numbers in China, it has become imperative to estimate the dynamics and cumulative infection...
·nature.com·
Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November–December 2022
The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures
The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures
COVID-19 causes neurological damage, systemic inflammation, and immune cell abnormalities. COVID-19-induced neurological impairment may be caused by s…
·sciencedirect.com·
The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures
Vaccine effectiveness against hospitalization among adolescent and pediatric SARS-CoV-2 cases between May 2021 and January 2022 in Ontario, Canada: A retrospective cohort study
Vaccine effectiveness against hospitalization among adolescent and pediatric SARS-CoV-2 cases between May 2021 and January 2022 in Ontario, Canada: A retrospective cohort study
Background Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations. Methods We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario’s Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron. Results We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p
·journals.plos.org·
Vaccine effectiveness against hospitalization among adolescent and pediatric SARS-CoV-2 cases between May 2021 and January 2022 in Ontario, Canada: A retrospective cohort study
Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies
Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies
The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric …
·sciencedirect.com·
Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies
Is there a Link between the 2021 COVID-19 Vaccination Uptake in Europe and 2022 Excess All-Cause Mortality?
Is there a Link between the 2021 COVID-19 Vaccination Uptake in Europe and 2022 Excess All-Cause Mortality?
We primarily study a possible link between 2021 COVID-19 vaccination uptake in Europe and monthly 2022 excess all-cause mortality, i.e., mortality higher than before the pandemic. Analyses of 31 countries weighted by population size show that all-cause mortality during the first nine months of 2022 increased more the higher the 2021 vaccination uptake; a one percentage point increase in 2021 vaccination uptake was associated with a monthly mortality increase in 2022 by 0.105 percent (95% CI, 0.075-0.134). When controlling for alternative explanations, the association remained robust, and we discuss the result emphasizing causality as well as potential ecological fallacy. Also, the study shows that 2021 all-cause mortality was lower the higher the vaccination uptake, but this association became non-significant when controlling for alternative explanations.
·preprints.org·
Is there a Link between the 2021 COVID-19 Vaccination Uptake in Europe and 2022 Excess All-Cause Mortality?
An Oral Galectin Inhibitor in COVID-19—A Phase II Randomized Controlled Trial
An Oral Galectin Inhibitor in COVID-19—A Phase II Randomized Controlled Trial
Background: SARS-CoV-2 vaccines play an important role in reducing disease severity, hospitalization, and death, although they failed to prevent the transmission of SARS-CoV-2 variants. Therefore, an effective inhibitor of galectin-3 (Gal-3) could be used to treat and prevent the transmission of COVID-19. ProLectin-M (PL-M), a Gal-3 antagonist, was shown to interact with Gal-3 and thereby prevent cellular entry of SARS-CoV-2 in previous studies. Aim: The present study aimed to further evaluate the therapeutic effect of PL-M tablets in 34 subjects with COVID-19. Methods: The efficacy of PL-M was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with mild to moderately severe COVID-19. Primary endpoints included changes in the absolute RT-PCR Ct values of the nucleocapsid and open reading frame (ORF) genes from baseline to days 3 and 7. The incidence of adverse events, changes in blood biochemistry, inflammatory biomarkers, and levels of antibodies against COVID-19 were also evaluated as part of the safety evaluation. Results: PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to a placebo treatment. On day 3, 14 subjects in the PL-M group had cycle counts for the N gene above the cut-off value of 29 (target cycle count 29), whereas on day 7, all subjects had cycle counts above the cut-off value. Ct values in placebo subjects were consistently less than 29, and no placebo subjects were RT-PCR-negative until day 7. Most of the symptoms disappeared completely after receiving PL-M treatment for 7 days in more patients compared to the placebo group. Conclusion: PL-M is safe and effective for clinical use in reducing viral loads and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through the inhibition of Gal-3.
·mdpi.com·
An Oral Galectin Inhibitor in COVID-19—A Phase II Randomized Controlled Trial
Real time analysis of SARS-CoV-2 induced cytolysis reveals distinct variant-specific replication profiles
Real time analysis of SARS-CoV-2 induced cytolysis reveals distinct variant-specific replication profiles
The continuous evolution of new SARS-CoV-2 variants with enhanced immune evasion capacity suggests the entire population is and will continue to be potentially vulnerable to infection despite pre-existing immunity. The ability of each new variant to evade host humoral immunity is the focus of intense research across the globe. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here we demonstrate the utility of a new approach to assessing viral replication kinetics using Real Time Cell Analysis (RTCA). Virus induced cell death is measured in real time by the detection of electrical impedance through cell monolayers. Using this system, we quantified replication kinetics of five clinically important viral variants; USA WA1/2020 (an A1 ancestral lineage isolate), Delta, and Omicron subvariants BA.1, BA.4, and BA.5. We identified multiple kinetic measures that proved useful in variant replication comparisons including time (in hours) to the maximum rate of cell death at each log10 viral dilution and the slope at the maximum rate of cell death. We found that WA1/2020 and Delta were the most rapid but in distinct ways. While WA1/2020 induced cell death most rapidly after inoculation, Delta was slightly slower to reach cell death, it appeared to kill cells faster once cytotoxic effects began. Interestingly, BA.1, showed substantially reduced replication kinetics relative to all other variants. Together, these data show that real time analysis of cell death is a robust method to assess replicative capacity of any given SARS-CoV-2 variant rapidly and quantitatively, which may be useful in assessment of newly emerging variants. ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
Real time analysis of SARS-CoV-2 induced cytolysis reveals distinct variant-specific replication profiles
The Effects of COVID-19 on the Placenta During Pregnancy
The Effects of COVID-19 on the Placenta During Pregnancy
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.
·frontiersin.org·
The Effects of COVID-19 on the Placenta During Pregnancy
Immungedächtnis nach SARS-CoV-2: Eine COVID-Infektion schützt mindestens so gut wie die Impfung
Immungedächtnis nach SARS-CoV-2: Eine COVID-Infektion schützt mindestens so gut wie die Impfung
Immunität muss reifen, die Entwicklung eines abwehrbereiten Immungedächtnisses benötigt Zeit. Das kann auch bei einer SARS-CoV-2-Infektion gut gelingen, wie aus einer aktuellen Metaanalyse hervorgeht. Mit dem Stichtag 28. Februar 2023 waren in...
·aerzteblatt.de·
Immungedächtnis nach SARS-CoV-2: Eine COVID-Infektion schützt mindestens so gut wie die Impfung
Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air - PubMed
Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air - PubMed
Coronavirus disease 2019 (COVID-19) spreads by airborne transmission; therefore, the development and functional evaluation of air-cleaning technologies are essential for infection control. Air filtration using high-efficiency particulate air (HEPA) filters may be effective; however, no quantitative …
·pubmed.ncbi.nlm.nih.gov·
Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air - PubMed