Past pandemic experience can affect health outcomes in future pandemics. This paper focuses on the last major influenza pandemic in 1968 (H3N2), which killed up to 100,000 people in the US. We find that places with high influenza mortality in 1968 experienced 1-4% lower COVID-19 death rates. Our identification strategy isolates variation in COVID-19 rates across people born before and after 1968. In places with high 1968 influenza incidence, older cohorts experience lower COVID-19 death rates relative to younger ones. The relationship holds using county and patient-level data, as well as in hospital and nursing home settings. Results do not appear to be driven by systemic or policy-related factors, instead suggesting an individual-level response to prior influenza pandemic exposure. The findings merit investigation into potential biological and immunological mechanisms that account for these differences–and their implications for future pandemic preparedness.
Objective: We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. Results: Among 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio (aHR) 1.12; 95% confidence interval (CI) 0.93; 1.34). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for boosted vs. no vaccine) were protective. Conclusion: Disease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective.
A number of studies have investigated the potential non-specific effects of some routinely administered vaccines (e.g. influenza, pneumococcal) on COVID-19 related outcomes, with contrasting results. In order to elucidate this discrepancy, we conducted a systematic review and meta-analysis to assess the association between seasonal influenza vaccination and pneumococcal vaccination with SARS-CoV-2 infection and its clinical outcomes. PubMed and medRxiv databases were searched, up until November 2021. Random effects model was used in the meta-analysis to pool odds ratio (OR) and adjusted estimates with their 95% confidence intervals (CIs). Heterogeneity was quantitatively assessed using the Cohran9s Q and the I2 index. Sub-group analysis, sensitivity analysis and assessment of publication bias were performed for all outcomes. In total 38 observational studies were included in the meta-analysis and there was substantial heterogeneity. Influenza and pneumococcal vaccination were associated with lower risk of SARS-Cov-2 infection (OR: 0.80, 95% CI: 0.75-0.86 and OR: 0.70, 95% CI: 0.57-0.88, respectively). Regarding influenza vaccination, it seems that the majority of studies did not properly adjust for all potential confounders, so when the analysis was limited to studies that adjusted for age, sex, comorbidities and socioeconomic indices, the association diminished. This is not the case regarding the pneumococcal vaccination, for which even after adjustment for such factors the association persisted. Regarding harder endpoints such as ICU admission and death, current data do not support the association. Possible explanations are discussed, including trained immunity, inadequate matching for socioeconomic indices and possible coinfection.
At the end of 2019, the new coronavirus, SARS-CoV-2, began a pandemic that persists to date and which has caused more than 6.2 million deaths. In the last couple of years, researchers have made great efforts to develop a diagnostic technique that maintains high levels of sensitivity and specificity, since an accurate and early diagnosis is required to minimize the prevalence of SARS-CoV-2 infection. In this context, CRISPR-Cas systems are proposed as promising tools for development in diagnostic techniques due to their high specificity, highlighting that Cas13 endonuclease discriminates single nucleotide changes and displays a collateral activity against single stranded RNA molecules. With the aim of improve the sensitivity of the diagnosis, this technology is usually combined with isothermal pre-amplification reactions (SHERLOCK, DETECTR). Basing on this, we have developed an RT-LAMP-CRISPR-Cas13a for SARS-CoV-2 virus detection in nasopharyngeal samples without using RNA extraction kit that exhibited 100 % specificity and 83 % sensitivity, as well as a positive predictive value of 100 % and a negative predictive value of 100%, 81%, 79.1% and 66.7 % in <20 Ct, 20-30 Ct, >30 Ct and total Ct values, respectively.
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults (≥18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
At the outset of the COVID-19 epidemic in the UK, infectious disease modellers advised the government that unless a lockdown was imposed, most of the population would be infected within a few months and critical care capacity would be overwhelmed. This paper investigates the quantitative arguments underlying these predictions, and draws lessons for future policy. The modellers assumed that within age bands all individuals were equally susceptible and equally connected, leading to predictions that more than 80% of the population would be infected in the first wave of an unmitigated epidemic. Models that relax this unrealistic assumption to allow for selective removal of the most susceptible and connected individuals predict much smaller epidemic sizes. In most European countries no more than 10% of the population was infected in the first wave, irrespective of what restrictions were imposed. The modellers assumed that about 2% of those infected would require critical care, far higher than the proportion who entered critical care in the first wave, and failed to identify the key role of nosocomial transmission in overloading health systems. Model-based forecasts that only a lockdown could suppress the epidemic relied on a survey of contact rates in 2006, with no information on the types of contact most relevant to aerosol transmission or on heterogeneity of contact rates. In future epidemics, modellers should communicate the uncertainties associated with their assumptions and data, especially when these models are used to recommend policies that have high societal costs and are hard to reverse. Recognition of the gap between models and reality also implies a need to rebalance in favour of greater reliance on rapid studies of real-world transmission, robust model criticism, and acceptance that when measurements contradict model predictions it is the model that needs to be changed.
Infection with SARS-CoV-2 induces COVID-19, an inflammatory disease that is usually self-limited, but depending on patient conditions may culminate with critical illness and patient death. The virus triggers activation of intracellular sensors, such as the NLRP3 inflammasome, which promotes inflammation and aggravates the disease. Thus, identification of host components associated with NLRP3 inflammasome is key for understanding the physiopathology of the disease. Here, we reported that SARS-CoV-2 induces upregulation and activation of human Caspase-4/CASP4 (mouse Caspase-11/CASP11) and this process contributes to inflammasome activation in response to SARS-CoV-2. CASP4 was expressed in lung autopsy of lethal cases of COVID-19 and CASP4 expression correlates with expression of inflammasome components and inflammatory mediators such as CASP1, IL1B, IL18 and IL6. In vivo infections performed in transgenic hACE2 humanized mouse, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with reduced body weight loss, reduced temperature variation, increased pulmonary parenchymal area, reduced clinical score of the disease and reduced mortality. Collectively, our data establishes that CASP4/11 contributes to disease pathology and contributes for future immunomodulatory therapeutic interventions to COVID-19.
Given the present pandemic and the constantly arising new variants of SARS-CoV-2, there is an urgent need to understand the factors driving disease evolution. Here, we investigate the tradeoff between the speed at which a disease progresses and its reproductive number. Using SEIR and agent-based models, we show that in the exponential growth phase of an epidemic, there will be an optimal duration of new disease variants, balancing the advantage of developing fast with the advantage of infecting many new people. In the endemic state this optimum disappears, and lasting longer is always advantageous for the disease. However, if we take into account the possibility of quarantining the infected, this leads to a new optimum disease duration emerging. This work thereby comments on the observation of ever shorter generation times in the evolution of variants of SARS-CoV-2 from the original strain to the Alpha, Delta, and finally Omicron variants.
Immuno-bridging Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition: COVID-19
Interventions: Biological: COVID-19 Protein Subunit Recombinant Vaccine; Biological: Active Comparator
Sponsors: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; Faculty of Medicine Universitas Diponegoro; Faculty of Medicine Universitas Andalas; Faculty of Medicine Universitas Hassanudin
Recruiting
A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised - Condition: COVID-19
Interventions: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir
Sponsor: Pfizer
Not yet recruiting
A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa. - Condition: COVID-19
Interventions: Device: Abbott Panbio rapid antigen self-tests; Other: COVIDSmart CARE! app
Sponsors: McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Cape Town Lung Institute
Not yet recruiting
Discussing COVID-19 Vaccines in Private Facebook Groups - Condition: COVID-19
Interventions: Behavioral: Gist messages on COVID-19 vaccination; Behavioral: COVID-19 vaccine information
Sponsor: George Washington University
Completed
Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated - Condition: COVID-19
Interventions: Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain; Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors: Sinovac Biotech (Colombia) S.A.S.; Sinovac Life Sciences Co., Ltd.
Not yet recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19 - Condition: Post SARS-CoV2 (COVID-19)
Intervention: Other: Tele-exercise
Sponsors: VA Office of Research and Development; Baltimore Veterans Affairs Medical Center; Salem Veterans Affairs Medical Center
Not yet recruiting
IMM-BCP-01 in Mild to Moderate COVID-19 - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Drug: IMM-BCP-01; Drug: Placebo
Sponsors: Immunome, Inc.; United States Department of Defense
Recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1) - Condition: COVID-19
Intervention: Biological: ABO1009-DP
Sponsor: Suzhou Abogen Biosciences Co., Ltd.
Not yet recruiting
A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines - Condition: COVID-19
Interventions: Biological: ABO1009-DP; Biological: ABO-CoV.617.2; Other: Placebo
Sponsor: Suzhou Abogen Biosciences Co., Ltd.
Not yet recruiting
Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions: COVID-19; Dysglycemia
Interventions: Drug: Insulin; Drug: Subcutaneous Insulin
Sponsor: Benha University
Completed
Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19. - Conditions: COVID-19 Pneumonia; COVID-19
Interventions: Biological: Mesenchymal stem cell; Other: Placebo
Sponsors: Paulo Brofman; Conselho Nacional de Desenvolvimento Científico e Tecnológico
Recruiting
A Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222 - Condition: COVID-19 Vaccine
Interventions: Biological: MVC-COV1901; Biological: AZD1222
Sponsor: Medigen Vaccine Biologics Corp.
Not yet recruiting
Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients - Conditions: Tension-Type Headache; Orofacial Pain; COVID-19
Intervention: Radiation: Photobimodulation
Sponsor: University of Nove de Julho
Recruiting
Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV) - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: GRT-R912, samRNA-Spikebeta-TCE11; Drug: GRT-R914, samRNA-Spikebeta-TCE9; Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11
Sponsor: Gritstone bio, Inc.
Recruiting
A Phase 1b Study of a Q-Griffithsin Intranasal Spray for Broad-spectrum Coronavirus Prophylaxis - Condition: COVID-19 Prevention
Interventions: Drug: Q-Griffithsin 3.0; Drug: Q-Griffithsin 6.0
Sponsors: Kenneth Palmer; United States Department of Defense
Recruiting
Rapid Assessment of Biological Activity of Ag-Based Antiviral Coatings for the Treatment of Textile Fabrics Used in Protective Equipment Against Coronavirus - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants have rapidly spread worldwide, causing coronavirus disease (COVID-19) with numerous infected cases and millions of deaths. Therefore, developing approaches to fight against COVID-19 is currently the most priority goal of the scientific community. As a sustainable solution to stop the spread of the virus, a green dip-coating method is utilized in the current work to prepare antiviral Ag-based coatings to treat cotton…
A pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa - CONCLUSION: LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.
A novel platform for attenuating immune hyperactivity using EXO-CD24 in Covid-19 and beyond - A small but significant proportion of Covid19 patients develop life-threatening cytokine storm. We have developed a new anti-inflammatory drug, EXO-CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF-kB pathway and the production of cytokines/chemokines. EXO-CD24 discriminates Damage- from Pathogen-Associated Molecular Patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO-CD24 was produced and purified from…
Antiviral effects of coinage metal-based nanomaterials to combat COVID-19 and its variants - The world has been suffering from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and millions of people have been infected through human-to-human transmission and lost their lives within months. Although multidisciplinary scientific approaches have been employed to fight against this deadly pandemic, various mutations and diverse environments keep producing constraints in treating SARS-CoV-2. Indeed, the efficacy of the developed vaccines has been limited, and…
Cepharanthine: A Promising Old Drug against SARS-CoV-2 - Recently, the inhibiting effects of a clinically approved drug Cepharanthine on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted widespread attention and discussion. However, the public does not understand the relevant research progress very well. This paper aims to introduce a brief history of studies on the effects of cepharanthine against SARS-CoV-2, including “discovery of anti-SARS-CoV-2 activity of cepharanthine in vitro”, "potential mechanisms of cepharanthine…
Therapeutic role of traditionally used Indian medicinal plants and spices in combating COVID-19 pandemic situation - The coronavirus disease (COVID-19) caused by SARS-CoV-2 is a big challenge and burning issue to the scientific community and doctors worldwide. Globally, COVID-19 has created a health disaster and adversely affects the economic growth. Although some vaccines have already emerged, no therapeutic medication has yet been approved by FDA for the treatment of COVID-19 patients. Traditionally, we have been using different medicinal plants like neem, tulsi, tea, and many spices like garlic, ginger,…
Structure basis for inhibition of SARS-CoV-2 by the feline drug GC376 - No abstract
Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release - Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines, chemokines and neutrophil extracellular traps (NETs). In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here…
Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial - BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.
The adverse inflammatory response of tobacco smoking in COVID-19 patients: biomarkers from proteomics and metabolomics - Whether tobacco smoking affects the occurrence and development of COVID-19 is still a controversial issue, and potential biomarkers to predict the adverse outcomes of smoking in the progression of COVID-19 patients have not yet been elucidated. To further uncover their linkage and explore the effective biomarkers, three proteomics and metabolomics databases (i.e. smoking status, COVID-19 status, and basic information of population) from human serum proteomic and metabolomic levels were…
The many facets of CD26/dipeptidyl peptidase 4 and its inhibitors in disorders of the CNS - a critical overview - Dipeptidyl peptidase 4 is a serine protease that cleaves X-proline or X-alanine in the penultimate position. Natural substrates of the enzyme are glucagon-like peptide-1, glucagon inhibiting peptide, glucagon, neuropeptide Y, secretin, substance P, pituitary adenylate cyclase-activating polypeptide, endorphins, endomorphins, brain natriuretic peptide, beta-melanocyte stimulating hormone and amyloid peptides as well as some cytokines and chemokines. The enzyme is involved in the maintenance of…
Identification of repurposing therapeutics toward SARS-CoV-2 main protease by virtual screening - SARS-CoV-2 causes the current global pandemic coronavirus disease 2019. Widely-available effective drugs could be a critical factor in halting the pandemic. The main protease (3CLpro) plays a vital role in viral replication; therefore, it is of great interest to find inhibitors for this enzyme. We applied the combination of virtual screening based on molecular docking derived from the crystal structure of the peptidomimetic inhibitors (N3, 13b, and 11a), and experimental verification revealed…
Spatially Patterned Neutralizing Icosahedral DNA Nanocage for Efficient SARS-CoV-2 Blocking - Broad-spectrum anti-SARS-CoV-2 strategies that can inhibit the infection of wild-type and mutant strains would alleviate their threats to global public health. Here, we propose an icosahedral DNA framework for the assembly of up to 30 spatially arranged neutralizing aptamers (IDNA-30) to inhibit viral infection. Each triangular plane of IDNA-30 is composed of three precisely positioned aptamers topologically matching the SARS-CoV-2 spike trimer, thus forming a multivalent spatially patterned…
An Overview on Immunity Booster Foods in Coronavirus Disease (COVID-19) - The present COVID-19 pandemic is highly terrible for the respiratory system and is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). It has affected millions of people globally and over 511.9 million cases and 6.2 million deaths have been reported across the world. Various drugs have been repurposed, however, no specific medicine has been approved by the FDA to combat this disease till date. In this condition, researchers have attracted to natural and safe products to…
C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus - The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde…