Background: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic. However, limited information is available from countries in sub-Saharan Africa (SSA). Evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are also scarce in these countries. The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. Methods: The PeriCOVID study is a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. A nasopharyngeal swab was taken from mothers at enrolment for RT-PCR confirmation of SARS-CoV-2 infection, and maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. The primary outcome was seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. Placental transfer of antibodies was described using the geometric mean ratio (GMR). We also estimated the proportion of asymptomatic or subclinical COVID-19 infections in pregnant women using serological testing, and collected adverse pregnancy and infancy outcomes (e.g. still-birth, prematurity, maternal or infant death). Results: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron) , in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes. Discussion: This study describes the increasing prevalence of SARS CoV-2 antibodies in pregnant woman in Uganda and Malawi across waves of SARS-CoV-2 infection. Our study adds to existing evidence that suggests under-reporting of infection if based solely on cases with clinical disease, or a positive RT-PCR for SARS-CoV-2, as most of the women in our study had asymptomatic infections and did not seek medical care. This has implications for screening in subsequent outbreaks and pandemics where protection of pregnant women and effect of infection in pregnancy on the infant are unknown.
Background The coronavirus disease 2019 (COVID-19) pandemic has put a strain on the healthcare system, and sudden changes in disease status during home treatment have become a serious issue. Therefore, prediction of disease severity and allocation of sufficient medical resources, including high-flow nasal cannula (HFNC), to patients in need are important. We aimed to determine risk factors for the need of HFNC use in COVID-19. Methods This was a single-center retrospective observational cohort study including all eligible hospitalized adult patients aged ≥18 years diagnosed with COVID-19 between April 14, 2020 and August 5, 2021 who were treated in the study hospital. The primary outcome was critical respiratory illness meeting one of the following criteria: oxygenation flow rate ≥ 10 L/min, high-flow oxygenation, noninvasive ventilation, invasive ventilation, and death. Nineteen potential predictive variables, including patient characteristics at hospital admission, were screened using least absolute shrinkage and selection operator and logistic regression to construct a predictive risk score. Accuracy of the risk score was determined using area under the receiver operating characteristic curve. Results The study cohort included 148 patients. The rate of critical respiratory illness was 22.9% (all patients needed high-flow device support). Among the 19 potential variables, percutaneous oxygen saturation (SpO2) <92% (odds ratio [OR] 7.50, 95% confidence interval [CI] 2.806–20.82) and IL-6 (OR 1.021, 95% CI 1.010–1.033) were included in developing the risk score, which was termed interleukin (IL)-6-based COVID-19 severity (IBC-S) score. Conclusions The IBC-S score, an easy-to-use risk score based on parameters available at the time of hospital admission, predicted critical respiratory failure in patients with COVID-19. In primary care settings, the IBC-S score based on interleukin-6 and SpO2 might aid in determining patients who should be transported to a tertiary medical institution or an isolation facility.
To design effective vaccines and other immune interventions against a pathogen, it is necessary to know which aspect of immunity associates with protection. We investigated whether neutralizing antibodies associate with infection clearance in long-term SARS-CoV-2 infection during HIV-mediated immunosuppression. We monitored neutralizing antibody activity against SARS-CoV-2 in five participants with advanced HIV disease and delayed control of HIV viremia. These participants had persistent SARS-CoV-2 infection ranging from 110 to 289 days which was associated with low or undetectable neutralizing antibody responses. SARS-CoV-2 clearance was associated with the emergence of neutralizing antibodies and occurred in two participants before suppression of HIV viremia, but after some CD4 T cell reconstitution. Vaccination only further increased neutralizing antibody levels in the advanced HIV disease participants who achieved HIV suppression pre-vaccination. During the prolonged SARS-CoV-2 infection we observed widespread evolution which was particularly pronounced in one Delta variant infection. This resulted in high-level escape from Delta-elicited neutralizing antibodies and a virus antigenically distinct from both ancestral SARS-CoV-2 and Omicron XBB in hamster experimental infections. The results offer new evidence that neutralizing antibodies associate with SARS-CoV-2 protection and argue that successful management of HIV may be necessary to curtail long-term infection and evolution of co-infecting pathogens.
Background: B-cell hypo-responsiveness has been associated with intestinal parasitic co-infection. The effect of parasite co-infection on antibody response to SARS-CoV-2 is unknown. Here, we aimed to determine antibody response to SARS-CoV-2 among COVID-19 patients co-infected with intestinal parasites and those without parasite co-infection. Methods: In this prospective cohort study, a total of 589 samples were serially collected from 72 RT-PCR-confirmed patients. Anti-SARS-CoV-2 nucleocapsid protein (NP) antibody titers were measured longitudinally during hospitalization. SARS-CoV-2 infection was confirmed by RT-PCR on samples obtained from nasopharyngeal swabs, while direct microscopic examination, modified Ritchie concentration, and Kato-Katz methods were used to identify parasites and ova from fresh stool samples. Data were analyzed using STATA version 14. Results: Of the 72 COVID-19 patients, 39 (54.2%) were co-infected with intestinal parasites while 33 (45.8%) had no parasitic co-infection. Overall, the median cut-off index (COI) for anti-NP antibody titer among COVID-19 patients co-infected with parasites was 6.91 (IQR: 0.55-40.7) compared to 7.51 (IQR: 0.21-59.21) in those without parasites (p=0.764). In addition, 174/261 [66.7% (95% CI: 60.68-72.16)] and 231/328 [70.4% (95% CI: 65.23-75.14)] specimens from COVID-19 patients with parasite co-infection and without parasites, respectively, had anti-SARS-CoV-2 antibody above the cut-off COI value (p=0.328). The positivity rate for anti-SARS-CoV-2 NP < 14 days after symptom onset was 66.3% (95% CI: 60.21-71.85) and 70.0% (95% CI: 64.72-74.74) for those not infected and co-infected with parasites, respectively (p=0.343). In addition, 31/72 (41.9%) of the patients who were negative at the time of enrollment were seroconverted. The trend in anti-NP antibodies among seroconverted individuals with and without parasites is also similar. Conclusions: Co-infection with parasitic infection has very little effect on the anti-SARS-CoV-2 antibody immune response. Further studies on the profile of neutralizing antibodies in parasite-endemic areas are warranted to ascertain vaccine efficacy.
The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 810 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
Background: Immune-suppressed solid organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. The highly infectious SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear. Methods: We characterized Spike-specific T cell responses to ancestral SARS-CoV-2, Omicron BA.4/5 and XBB.1.5 peptides in a prospective study of kidney, lung and liver transplant recipients (n = 42) throughout a three- or four-dose ancestral Spike mRNA vaccination schedule. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4+ and CD8+ T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137 and/or CD107a. Results: Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to Omicron BA.4/5 and XBB.1.5 were significantly lower in magnitude compared to ancestral strain responses. Antigen-specific CD4+ T cell frequencies correlated with anti-receptor-binding domain (RBD) antibody titres, with post-second dose T cell responses predicting subsequent antibody responses. Patients receiving prednisone, lung transplant recipients and older adults displayed weaker responses. Conclusions: Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but responses to these variants are diminished. Antigen-specific T cells can predict future antibody responses and identify vaccine responses in seronegative individuals. Our data support monitoring both humoral and cellular immunity in SOTRs to track effectiveness of COVID-19 vaccines against emerging variants.
Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known. Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for cardiometabolic diagnoses by 18 months after birth, compared with unexposed offspring born during the COVID-19 pandemic. Design. This retrospective cohort study included the live offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020 - December 31, 2021) at 8 hospitals within 2 health systems in Massachusetts. Exposure. SARS-CoV-2 positivity on polymerase chain reaction (PCR) test during pregnancy. Main Outcome Measures. Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to cardiometabolic disorders. Offspring weight-for-age, length-for-age, and body mass index (BMI)-for-age z-scores at birth, 6 months, 12 months, and 18 months of age. Results. The full study cohort includes 29,510 live born offspring (1,599 exposed and 27,911 unexposed offspring). 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis by 18 months of age (crude OR 1.47 [95% CI: 1.10-1.94], p=0.007; adjusted OR 1.37 [1.01-1.83]; p=0.04). These diagnoses were preceded by significantly greater mean BMI-for-age z-scores in exposed versus unexposed offspring at 6 months (mean z-score difference 0.19, 95% CI: 0.10, 0.29, p<0.001), and a greater proportion of offspring at risk of, or meeting criteria for, overweight/obesity (16.5% vs. 12.2%, p=0.006). Conclusions. Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months and greater BMI-for-age at 6 months.
We administered BNT162b2 as a third dose to 314 adults ≥30 years of age who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1, 6 and 12 months, and found stable levels of antibody responses to the ancestral strain and Omicron BA.2 at 6-12 months after receipt of the BNT162b2 third dose, with increased antibody levels in individuals who also received a fourth vaccine dose or reported a SARS-CoV-2 infection during follow-up.
People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March – October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n=12), secondary immunosuppression (N=8) and those with primary or acquired immunodeficiency (i.e. HIV; N=7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.
Purpose: Retail workers are an understudied occupational group that may have been at increased risk of contracting SARS-CoV-2 during the COVID-19 pandemic. Therefore, we set up a longitudinal cohort of participants working in this sector to better document the incidence of SARS-CoV-2 infection and the immune response to infection and/or vaccination in this group. Participants: A total of 304 participants were recruited between April 20, 2021 and October 22, 2021. They were invited to attend three visits (each separated by ~12 weeks) during which they provided blood samples and information on participant characteristics, COVID-19 symptoms, and vaccination. An extension phase of two additional visits was carried out between March 15th, 2022 and October 3rd, 2022 to document the impact of the Omicron variant among the 198 participants who were still eligible for recruitment. Participants were aged 18 to 75 and worked in grocery stores, hardware stores, bars or restaurants within the Quebec City metropolitan area (Canada). Findings to date: This article describes participants9 demographic, socioeconomic, behavioral, clinical and occupational characteristics, and their COVID-19 symptoms (where applicable). It also describes SARS-CoV-2 vaccination status and any SARS-CoV-2 diagnostic test (i.e., PCR or rapid antigen) performed from the beginning of the pandemic until the last visit. Future plans: The incidence of SARS-CoV-2 infections will be assessed. The immune response (innate and acquired) to SARS-CoV-2 infection or vaccination will be studied using a variety of techniques, including reference and experimental enzyme-linked immunosorbent assays, microneutralization assays with live viruses, experimental pseudoneutralization with an angiotensin-converting enzyme 2-spike assay, peripheral blood mononuclear cells and neutrophil stimulation, and a proliferation assay based on carboxyfluorescein diacetate succinimidyl ester.
Objective: To determine the clinical and laboratory characteristics, as well as evaluating the factors associated with mortality in patients with COVID-19 infection and acute kidney injury (AKI) hospitalized in the Intensive Care Unit (ICU) of the Hospital Nacional Arzobispo Loayza. Materials and Methods: Retrospective cohort study, with convenience sampling during the period from April 2020 to March 2021, through the review of medical records data. Inclusion criteria were; patients ≥ 18 years old, with a diagnosis of COVID-19 infection, who were admitted to ICU with normal renal function and developed AKI during their stay in ICU. Exclusion criteria were; patients who developed AKI prior to ICU admission, patients with chronic kidney disease with and without dialysis. Results: A total of 177 medical records that met the inclusion and exclusion criteria were evaluated. The mean age was 57.2+/-13.2 years, 145 (81.4%) were male; comorbidities were: obesity 112(63.3%), arterial hypertension 55 (31.1%) and diabetes mellitus 30(16.9%); the most frequent cause of AKI was hypoperfusion (93%). 83 participants (46.8%) received dialytic support in the intermittent hemodialysis modality. In-hospital mortality was 151 (85.3%) and was higher in the group with stage 3 AKI: 109 (72.2%). The increase in ferritin level (OR: 10.04 (95%CI 4.4-38.46), p<0.001) and APACHE score (OR: 1.75 (95%CI 1.4-2.12), p<0.001), as well as the decrease in PaO2/FiO2 level (OR: 0.85 (95%CI 0.59-0.92), p<0.041, were related to mortality. Conclusions: AKI in ICU patients with COVID-19 infection has a high mortality and the related factors were the increase in APACHE II score and ferritin level, as well as the decrease in PaO2/FiO2 level. Keywords: Acute kidney injury, COVID-19, Intensive care units (MeSH)
Background: Decisions to impose temporary travel measures are less common as the global epidemiology of COVID-19 evolves. Risk-based travel measures may avoid the need for a complete travel ban, however evaluations of their effects are lacking. Here we investigated the public health effects of a temporary traffic light system introduced in the United Kingdom (UK) in 2021, imposing red-amber-green (RAG) status based on risk assessment. Methods: We analysed data on international flight passengers arriving into Scotland, COVID-19 testing surveillance, and SARS-CoV-2 whole genome sequences to quantify effects of the traffic light system on (i) international travel frequency, (ii) travel-related SARS-CoV-2 case importations, (iii) national SARS-CoV-2 case incidence, and (iv) importation of novel SARS-CoV-2 variants. Results: International flight passengers arriving into Scotland had increased by 754% during the traffic light period. Amber list countries were the most frequently visited and ranked highly for SARS-CoV-2 importations and contribution to national case incidence. Rates of international travel and associated SARS-CoV-2 cases varied significantly across age, health board, and deprivation groups. Multivariable logistic regression revealed SARS-CoV-2 cases detections were less likely among travellers than non-travellers, although increasing from green-to-amber and amber-to-red lists. When examined according to travel destination, SARS-CoV-2 importation risks did not strictly follow RAG designations, and red lists did not prevent establishment of novel SARS-CoV-2 variants. Conclusions: Our findings suggest that country-specific post-arrival screening undertaken in Scotland did not prohibit the public health impact of COVID-19 in Scotland. Travel rates likely contributed to patterns of high SARS-CoV-2 case importation and population impact.
Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.
Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: COVID-19
Intervention: Drug: Obeldesivir
Sponsor: Gilead Sciences
Not yet recruiting
EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition: Post-COVID-19 Syndrome
Intervention: Behavioral: rehacom
Sponsor: Cairo University
Enrolling by invitation
Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A COVID-19 Preventive Vaccine in Healthy Volunteers - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI; Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
Sponsor: Cellid Co., Ltd.
Not yet recruiting
Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions: Vaccination Hesitancy; COVID-19
Interventions: Behavioral: Behavioural science-informed text messages; Behavioral: Control
Sponsors: The Behavioural Insights Team; Public Health England; Department of Health and Social Care; NHS England and NHS Improvement
Completed
Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: Ivermectin; Drug: Placebo
Sponsor: Insud Pharma
Terminated
Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition: Post-COVID-19 Syndrome
Intervention: Drug: Methylprednisolone
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy
Intervention: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
Sponsors: Duke University; American Society of Hematology
Not yet recruiting
A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions: SARS CoV 2 Infection; Influenza, Human
Interventions: Biological: BIMERVAX; Biological: SIIV
Sponsor: Hipra Scientific, S.L.U
Not yet recruiting
Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions: Mental Health; COVID-19; Misinformation
Interventions: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging
Sponsors: Harvard Medical School (HMS and HSDM); Partners in Health
Active, not recruiting
A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Biological: BNT162b2 (Omi XBB.1.5)
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Pulmonary Artery Pressure in COVID-19 Survivors - Condition: Pulmonary Hypertension Secondary
Intervention: Diagnostic Test: right heart catheterization (RHC).
Sponsor: Mansoura University Hospital
Enrolling by invitation
Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions: Cardiovascular Health; Physical Function
Intervention: Behavioral: Golden Circle
Sponsor: University of Illinois at Urbana-Champaign
Completed
Supported Employment COVID-19 Rapid Testing for PWID - Condition: Health Behavior
Intervention: Behavioral: Supported Employment
Sponsor: University of Oregon
Not yet recruiting
Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 - Condition: Coronavirus Infections
Interventions: Drug: tixagevimab/cilgavimab 150+150 mg; Drug: tixagevimab/cilgavimab 300+300 mg; Drug: regdanvimab
Sponsors: City Clinical Hospital No.52 of Moscow Healthcare Department; Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Active, not recruiting
Study of LAU-7b for the Treatment of Long COVID in Adults - Condition: Long COVID
Interventions: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles
Sponsor: Laurent Pharmaceuticals Inc.
Not yet recruiting
Peptide foldamer-based inhibitors of the SARS-CoV-2 S protein-human ACE2 interaction - The entry of the SARS-CoV-2 virus into a human host cell begins with the interaction between the viral spike protein (S protein) and human angiotensin-converting enzyme 2 (hACE2). Therefore, a possible strategy for the treatment of this infection is based on inhibiting the interaction of the two abovementioned proteins. Compounds that bind to the SARS-CoV-2 S protein at the interface with the alpha-1/alpha-2 helices of ACE2 PD Subdomain I are of particular interest. We present a stepwise…
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis - Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and…
Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-modifying Therapies - Respiratory virus infections initiate and transmit from the upper respiratory tract (URT). Coronaviruses, including OC43, are a major cause of respiratory infection and disease. Failure to mount an effective anti-viral immune response in the nasal mucosa increases the risk of severe disease and person to person transmission highlighting the need for URT infection models to support development of nasal treatments that improve coronavirus anti-viral immunity. We aimed to determine if OC43…
The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community - SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in…
Management of chronic myelogenous leukemia with COVID-19 and hepatitis B - The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and…
Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance - CONCLUSIONS: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.
Neutralizing antibody and T-cell responses against SARS-CoV-2 variants by heterologous CoronaVac/ChAdOx-1 vaccination in elderly subjects with chronic obstructive pulmonary disease - CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen.
Cysteamine-mediated blockade of the glycine cleavage system modulates epithelial cell inflammatory and innate immune responses to viral infection - Transient blockade of glycine decarboxylase (GLDC) can restrict de novo pyrimidine synthesis, which is a well-described strategy for enhancing the host interferon response to viral infection and a target pathway for some licenced anti-inflammatory therapies. The aminothiol, cysteamine, is produced endogenously during the metabolism of coenzyme A, and is currently being investigated in a clinical trial as an intervention in community acquired pneumonia resulting from viral (influenza and…
Bioengineered Neutrophil Extinguisher Targets Cascade Immune Pathways of Macrophages for Alleviating Cytokine Storm in Pneumonia - Cytokine storm is a common complication of COVID-19 pneumonia and has been proven to contribute to high mortality rates. However, current treatment approaches exhibit limited potential to balance immune response and overproduction of inflammatory cytokines, leading to poor therapeutic outcomes. Herein, a smart bioengineered neutrophil, Extinguisher, composed of live neutrophils encapsulating the liposome formulation of NF-κB suppressor MLN4924 and STING inhibitor H-151 (Lip@MH), is developed for…
Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys - Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming the bioactive triphosphate 2-NTP. 2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for 1 have prompted interest in oral approaches to generate 2-NTP. Here, we describe the discovery of a 5’-isobutyryl ester prodrug of 2 (GS-5245, Obeldesivir, 3) that has low cellular…
Novel mono- and multivalent N-acetylneuraminic acid glycoclusters as potential broad-spectrum entry inhibitors for influenza and coronavirus infection - N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density-dependent fashion. Compared with inhibition by Neu5Ac,…
Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides - The COVID-19 pandemic has caused significant global impact, resulting in long-term health effects for many individuals. As more patients recover, there is a growing need to identify effective management strategies for ongoing health concerns, such as post-COVID-19 syndrome, characterized by persistent symptoms or complications beyond several weeks or months from the onset of symptoms. In this review, we explore the potential of dietary polysaccharides as a promising approach to managing…
Alkyne as a Latent Warhead to Covalently Target SARS-CoV-2 Main Protease - There is an urgent need for improved therapy to better control the ongoing COVID-19 pandemic. The main protease M^(pro) plays a pivotal role in SARS-CoV-2 replications, thereby representing an attractive target for antiviral development. We seek to identify novel electrophilic warheads for efficient, covalent inhibition of M^(pro). By comparing the efficacy of a panel of warheads installed on a common scaffold against M^(pro), we discovered that the terminal alkyne could covalently modify…
Discovery and Mechanism Study of SARS-CoV-2 3C-like Protease Inhibitors with a New Reactive Group - 3CL^(pro) is an attractive target for the treatment of COVID-19. Using the scaffold hopping strategy, we identified a potent inhibitor of 3CL^(pro) (3a) that contains a thiocyanate moiety as a novel warhead that can form a covalent bond with Cys145 of the protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed the mechanism of covalent formation between 3a and the protein in its catalytic pocket. Moreover, several analogues of compound 3a were designed and synthesized….
Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum - Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and…