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1.
BJOG ; 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1774705

ABSTRACT

OBJECTIVE: On a population basis, we assessed medical care for pregnant women in specific geographic regions of six countries before and during the first year of the COVID-19 pandemic in relationship to pregnancy outcomes. DESIGN: Prospective, population-based study. SETTING: Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India, and Guatemala. POPULATION: Pregnant women enrolled in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry METHODS: Pregnancy/delivery care services and pregnancy outcomes in the pre-COVID-19 time-period (March 2019-February 2020) were compared to the COVID-19 time-period (March 2020-February 2021). MAIN OUTCOME MEASURES: Stillbirth, neonatal mortality, preterm birth, low birth weight, maternal mortality RESULTS: Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID and COVID periods. (18.9% vs 20.3%, aRR 1.12 95% CI 1.05, 1.19). Also, a small but significant decrease in the mean number of antenatal care visits (4.1 - 4.0, p= <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight in the COVID-19 period occurred (15.7% vs 14.6%, aRR 0.94 (0.89, 0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. CONCLUSIONS: Small but significant increases in home births and decreases in the ANC services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birth weight or preterm birth rates during the COVID-19 period as compared to the prior year. Further research should help elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period.

3.
NPJ Vaccines ; 6(1): 137, 2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1526080

ABSTRACT

We developed a SARS-CoV-2 spike subunit vaccine formulation containing dual TLR ligand liposome adjuvant. The vaccine-induced robust systemic neutralizing antibodies and completely protected mice from a lethal challenge. Two immunizations protected against lung injury and cleared the virus from lungs upon challenge. The adjuvanted vaccine also elicited systemic and local anti-Spike IgA which can be an important feature for a COVID-19 vaccine.

4.
JCI Insight ; 6(15)2021 08 09.
Article in English | MEDLINE | ID: covidwho-1286768

ABSTRACT

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2-infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13-induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13-mediated HA synthesis in pulmonary pathology.


Subject(s)
COVID-19/immunology , Interleukin-13/immunology , SARS-CoV-2/immunology , Animals , COVID-19/blood , COVID-19/pathology , COVID-19/therapy , Disease Models, Animal , Disease Progression , Female , Humans , Interleukin-13/blood , Lung/immunology , Lung/pathology , Male , Mice , Mice, Inbred C57BL , Severity of Illness Index
5.
mBio ; 12(3): e0122921, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1286719

ABSTRACT

We sought to discover links between antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient clinical variables, cytokine profiles, and antibodies to endemic coronaviruses. Serum samples from 30 patients of younger (26 to 39 years) and older (69 to 83 years) age groups and with varying clinical severities ranging from outpatient to mechanically ventilated were collected and used to probe a novel multi-coronavirus protein microarray. This microarray contained variable-length overlapping fragments of SARS-CoV-2 spike (S), envelope (E), membrane (M), nucleocapsid (N), and open reading frame (ORF) proteins created through in vitro transcription and translation (IVTT). The array also contained SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), and HCoV-NL63 proteins. IgG antibody responses to specific epitopes within the S1 protein region spanning amino acids (aa) 500 to 650 and within the N protein region spanning aa 201 to 300 were found to be significantly higher in older patients and further significantly elevated in those older patients who were ventilated. Additionally, there was a noticeable overlap between antigenic regions and known mutation locations in selected emerging SARS-CoV-2 variants of current clinical consequence (B.1.1.7, B1.351, P.1, CAL20.C, and B.1.526). Moreover, the older age group displayed more consistent correlations of antibody reactivity with systemic cytokine and chemokine responses than the younger adult group. A subset of patients, however, had little or no response to SARS-CoV-2 antigens and disproportionately severe clinical outcomes. Further characterization of these slow-low-responding individuals with cytokine analysis revealed significantly higher interleukin-10 (IL-10), IL-15, and interferon gamma-induced protein 10 (IP-10) levels and lower epidermal growth factor (EGF) and soluble CD40 ligand (sCD40L) levels than those of seroreactive patients in the cohort. IMPORTANCE As numerous viral variants continue to emerge in the coronavirus disease 2019 (COVID-19) pandemic, determining antibody reactivity to SARS-CoV-2 epitopes becomes essential in discerning changes in the immune response to infection over time. This study enabled us to identify specific areas of antigenicity within the SARS-CoV-2 proteome, allowing us to detect correlations of epitopes with clinical metadata and immunological signals to gain holistic insight into SARS-CoV-2 infection. This work also emphasized the risk of mutation accumulation in viral variants and the potential for evasion of the adaptive immune responses in the event of reinfection. We additionally highlighted the correlation of antigenicity between structural proteins of SARS-CoV-2 and endemic HCoVs, raising the possibility of cross-protection between homologous lineages. Finally, we identified a subset of patients with minimal antibody reactivity to SARS-CoV-2 infection, prompting discussion of the potential consequences of this alternative immune response.


Subject(s)
Antibodies, Viral/blood , Coronavirus NL63, Human/immunology , Coronavirus OC43, Human/immunology , Cytokines/blood , Middle East Respiratory Syndrome Coronavirus/immunology , SARS-CoV-2/immunology , Adult , Age Factors , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , Coronavirus Envelope Proteins/immunology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoglobulin G/immunology , Male , Phosphoproteins/immunology , Protein Array Analysis , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology
6.
Clin Infect Dis ; 72(12): 2225-2240, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-889502

ABSTRACT

In this article, the editors of Clinical Infectious Diseases review some of the most important lessons they have learned about the epidemiology, clinical features, diagnosis, treatment and prevention of SARS-CoV-2 infection and identify essential questions about COVID-19 that remain to be answered.


Subject(s)
COVID-19 , Humans , SARS-CoV-2
7.
Am J Trop Med Hyg ; 103(3): 1215-1219, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-690862

ABSTRACT

Murine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19. Because human angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for 5 days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day 4, when no other obvious clinical symptoms other than weight loss were observed. By day 5, all infected mice had lost around 10% of their original body weight but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration, and alveolar septal thickening. Overall, these results show that the K18-hACE2 transgenic background can be used to establish symptomatic SARS-CoV-2 infection and can be a useful mouse model for COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/etiology , Disease Models, Animal , Keratin-18/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/etiology , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Humans , Male , Mice , Mice, Transgenic , Pandemics , SARS-CoV-2
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