The biology driving individual patient responses to SARS-CoV-2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data, covering a year post disease onset, from 215 SARS-CoV-2 infected subjects with differing disease severities. Our analyses revealed distinct “systemic recovery” profiles with specific progression and resolution of the inflammatory, immune, metabolic and clinical responses, over weeks to several months after infection. In particular, we found a strong intra-patient temporal covariation of innate immune cell numbers, kynurenine- and host lipid-metabolites, which suggested candidate immunometabolic pathways putatively influencing restoration of homeostasis, the risk of death and of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery on the patient level, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-systemic-recovery-prediction-app, designed to test our findings prospectively.
Abstract Introduction Contemporary literature has revealed that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes acute sialadenitis and related symptoms, such as discomfort, pain, swelling, and secretory dysfunction in salivary glands. The secretory dysfunction is due to SARS-CoV-2 infection-induced xerostomia and other associated clinical courses such as sore tongue, mucosal ulcer, and gingivitis in the oral cavity. Furthermore, it has been reported that COVID-19 causes the development of other oral manifestations. Materials and Methods A prospective clinical follow-up (a prevalent cohort) study was conducted to identify the possible oral manifestations of SARS-CoV-2 infection among patients admitted at the Eka General Hospital COVID-19 treatment center. Furthermore, the study aimed to calculate the prevalence rate of oral clinical courses in the cohorts. The study had two follow-up phases: Hospital and patient-home-based. Results A total of 55 patients (36 males and 19 females) met the inclusion criteria and were followed for 7.5 weeks. The 3.5 weeks’ hospital-based prospective follow-up study documented an 18% (n=10) prevalence rate of oral clinical courses among the cohorts. Twelve oral symptoms appeared in these ten patients. The manifested oral symptoms were oral mucosal lesions (n=6), xerostomia (n=5), and thickening of saliva (n=1). The oral mucosal lesions per se consisted of aphthous lesions (n=3), candidiasis (n=1), geographic tongue (n=1), and localized gingivitis (n=1). On the other hand, the four weeks’ home-based follow-up study disclosed four newly manifested oral symptoms: hemorrhagic crust, bulla, buccal mucositis, and petechiae. These manifestations appeared among six patients (four males and two females) who had not manifested any oral symptoms during the hospital-based follow-up. Accordingly, the overall prevalence of oral clinical courses among patients presented with SARS-CoV-2 is raised from 18% (n=10) to 29% (n=16). Similarly, the number of clinical courses increased from 12 to 16 after four additional weeks of follow-up. Discussion The study9s findings suggest the importance of initiating oral health care for patients with COVID-19. Therefore, multidisciplinary healthcare approaches should be delivered to assure optimal health outcomes. Accordingly, oral health professionals must be a substantial part of the interdisciplinary approach in caring for patients with COVID-19.
Background Determining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models. Methods We analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitter9s decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data. Results Anomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses. Conclusions Our results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention.
Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition: COVID-19 Pneumonia
Interventions: Biological: Experimental Vaccine 1; Biological: Experimental Vaccine 2; Biological: Experimental Vaccine 3; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
COVID-19 Algorithm Treatment at Home - Condition: COVID-19
Interventions: Drug: Recommended treatment schedule; Drug: Usual care
Sponsor: Mario Negri Institute for Pharmacological Research
Not yet recruiting
Immunosuppression and COVID-19 Boosters - Condition: COVID-19
Interventions: Biological: diphtheria and tetanus toxoids (adsorbed) vaccine; Biological: COVID-19 vaccine
Sponsors: Kirby Institute; Seqirus Pty Ltd, Australia; Medical Research Future Fund (MRFF)
Not yet recruiting
Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition: COVID-19
Intervention: Other: telephone interview 24 months after hospitalization for Covid-19
Sponsor: Centre Hospitalier Universitaire de la Réunion
Not yet recruiting
Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition: COVID-19 Vaccines
Interventions: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Recruiting
Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
Sponsor: Sinovac Biotech (Hong Kong) Limited
Not yet recruiting
Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19
Interventions: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo
Sponsor: 4Living Biotech
Not yet recruiting
Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. - Condition: Men Infertility, Post-COVID-19
Intervention: Other: diagnostic test and sperm analysis
Sponsors: Comenius University; GYN-FIV
Active, not recruiting
Calcitriol Supplementation in COVID-19 Patients - Conditions: COVID-19; Vitamin D Deficiency
Intervention: Drug: Calcitriol
Sponsor: RenJi Hospital
Not yet recruiting
Olfactory Training in COVID-19 Associated Loss of Smell - Conditions: COVID-19; Hyposmia
Intervention: Device: Sniffin’ sticks Duftquartett
Sponsor: Medical University Innsbruck
Not yet recruiting
Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19 - Conditions: COVID-19; Stress Disorders, Post-Traumatic
Interventions: Other: Revised Impact of Event Scale; Other: Hospital Anxiety and Depression scale; Other: 36-Item Short Form Survey; Other: satisfaction survey; Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation; Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care
Sponsor: Centre Hospitalier Metropole Savoie
Completed
Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions: COVID-19; Type 2 Diabetes Mellitus
Intervention: Other: Aerobic and Relaxation Exercises
Sponsor: Bozyaka Training and Research Hospital
Active, not recruiting
COVID-19 Vaccine Uptake Trial - Conditions: Vaccination Refusal; COVID-19
Interventions: Other: Short Message Service (SMS) + Website Link Strategy; Other: Phone Call with Peer Strategy
Sponsor: Washington University School of Medicine
Not yet recruiting
Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome - Conditions: Post-acute COVID-19 Syndrome; Postural Tachycardia Syndrome (POTS); Long COVID; SARS CoV 2 Infection
Interventions: Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients; Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation); Diagnostic Test: Autonomic Symptoms assessment
Sponsors: Vanderbilt University Medical Center; American Heart Association
Recruiting
Inhibition of Bradykinin in COVID-19 Infection With Icatibant - Condition: SARS CoV 2 Infection
Interventions: Drug: Icatibant; Drug: 0.9% Sodium Chloride Injection
Sponsors: Belfast Health and Social Care Trust; Queen’s University, Belfast
Recruiting
Humoral and Cellular Responses to BNT162b2 as a Booster Following Two Doses of ChAdOx1 nCov-19 Determined Using Three SARS-CoV-2 Antibody Assays and an Interferon-Gamma Release Assay: A Prospective Longitudinal Study in Healthcare Workers - Data on humoral and cellular responses to BNT162b2 as a booster dose, following two doses of ChAdOx1 nCov-19 vaccine, have seldom been reported. The aim of this study was to assess the positivity rates of three representative antibody assays targeting total, IgG, and neutralizing antibodies, and an interferon-γ release assay (IGRA), and to determine the longitudinal changes in quantitative antibody titers after each vaccination. A total of 1027 samples were collected from healthcare workers. The…
Mechanism of CK2 Inhibition by a Ruthenium-Based Polyoxometalate - CK2 is a Ser/Thr protein kinase involved in many cellular processes such as gene expression, cell cycle progression, cell growth and differentiation, embryogenesis, and apoptosis. Aberrantly high CK2 activity is widely documented in cancer, but the enzyme is also involved in several other pathologies, such as diabetes, inflammation, neurodegeneration, and viral infections, including COVID-19. Over the last years, a large number of small-molecules able to inhibit the CK2 activity have been…
Calcium bicarbonate as an antimicrobial, antiviral, and prion-inhibiting agent (Review) - Calcium bicarbonate does not act as a disinfectant at neutral pH; however, it exerts strong antimicrobial activity after it is placed in a high-voltage electric field, whereby it assumes an alkaline pH (12.4). Moreover, the microbicidal activity of the resulting solution (named CAC-717) is not influenced by the presence of organic material or resistance of the agent to inactivation. When sprayed on the skin surface, the pH of CAC-717 decreases rapidly to 8.84. CAC-717 comprises fine particles of…
Streptomyces BAC Cloning of a Large-Sized Biosynthetic Gene Cluster of NPP B1, a Potential SARS-CoV-2 RdRp Inhibitor - As valuable antibiotics, microbial natural products have been in use for decades in various fields. Among them are polyene compounds including nystatin, amphotericin, and nystatin-like Pseudonocardia polyenes (NPPs). Polyene macrolides are known to possess various biological effects, such as antifungal and antiviral activities. NPP A1, which is produced by Pseudonocardia autotrophica, contains a unique disaccharide moiety in the tetraene macrolide backbone. NPP B1, with a heptane structure and…
In vitro study on efficacy of PHELA, an African traditional drug against SARS-CoV-2 - In 2019, coronavirus has made the third apparition in the form of SARS-CoV-2, a novel strain of coronavirus that is extremely pathogenic and it uses the same receptor as SARS-CoV, the angiotensin-converting enzyme 2 (ACE2). However, more than 182 vaccine candidates have been announced; and 12 vaccines have been approved for use, although, even vaccinated individuals are still vulnerable to infection. In this study, we investigated PHELA, recognized as an herbal combination of four exotic African…
Identification of potent inhibitors of arenavirus and SARS-CoV-2 exoribonucleases by fluorescence polarization assay - Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proofreading mechanism ensuring the genetic stability of the viral genome. Because of their key roles in virus life cycle, they constitute attractive…
Microneedle-based Two-step Transdermal Delivery of Langerhans cell-targeting Immunoliposomes Induces a Th1-biased Immune response - Novel Coronavirus is affecting human’s life globally and vaccines are one of the most effective ways to combat the epidemic. Transcutaneous immunization based on microneedle (MN) has attracted much attention because of its painlessness, rapidity, high efficiency and good compliance. In this study, CD11c monoclonal antibody-immunoliposomes (OVA@CD11c-ILP) actively targeting to Langerhans cells (LCs) were successfully prepared and were delivered by the microchannels of skin produced by MN to…
Synergistic interactions of repurposed drugs that inhibit Nsp1, a major virulence factor for COVID-19 - Nsp1 is one of the first proteins expressed from the SARS-CoV-2 genome and is a major virulence factor for COVID-19. A rapid multiplexed assay for detecting the action of Nsp1 was developed in cultured lung cells. The assay is based on the acute cytopathic effects induced by Nsp1. Virtual screening was used to stratify compounds that interact with two functional Nsp1 sites: the RNA-binding groove and C-terminal helix-loop-helix region. Experimental screening focused on compounds that could be…
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants - A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet…
Preadmission Statin Treatment and Outcome in Patients Hospitalized With COVID-19 - Preadmission statin therapy is associated with improved outcome in patients hospitalized with COVID-19. Whether inhibition of inflammation and myocardial injury are in part responsible for this observation has not been studied. The aim of the present study was to relate preadmission statin usage to markers of inflammation, myocardial injury, and clinical outcome among patients with established atherosclerosis who were admitted with COVID-19. Adult patients with a diagnosis of coronary artery…
Quinic and digallic acids from Pistacia atlantica Desf. leaves extracts as potent dual effect inhibitors against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 - CONCLUSION: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves is studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.
Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some Nitrogen Heterocyclic Compounds Targeting Proteins Involved in Development of COVID-19 - CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.
Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide - Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential…
Overview of Breastfeeding Under COVID-19 Pandemic - During the global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnant and lactating women are at higher risk of infection. The potential of viral intrauterine transmission and vertical transmission by breastfeeding has raised wide concerns. Breastmilk is rich in nutrients that contribute to infant growth and development, and reduce the incidence rate of infant illness and death, as well as inhibit pathogens…
Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection - Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented…