MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Pre-existing immunity to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, induced from natural infection or vaccination. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. Here we compare serum antibody and memory B cell responses to coronavirus spike proteins from pre-pandemic and SARS-CoV-2 convalescent donors using binding and functional assays. We show weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we find evidence of pre-existing cross-reactive memory B cells that are activated during SARS-CoV-2 infection. Monoclonal antibodies show varying degrees of cross-reactivity with betacoronaviruses, including SARS-CoV-1 and endemic coronaviruses. We identify one cross-reactive neutralizing antibody specific to the S2 subunit of the S protein. Our results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.

/pdf/cross-reactive-serum-and-memory-b-cell-responses-to-spike-3p5nbwsko5.pdf

Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection.

Pre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, either induced in natural infection or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. We compared serum antibody and memory B cell responses to coronavirus spike (S) proteins from pre-pandemic and SARS-CoV-2 convalescent donors using a series of binding and functional assays. We found weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we found stronger evidence of pre-existing cross-reactive memory B cells that were activated on SARS-CoV-2 infection. Monoclonal antibodies (mAbs) isolated from the donors showed varying degrees of cross-reactivity with betacoronaviruses, including SARS and endemic coronaviruses. None of the cross-reactive mAbs were neutralizing except for one that targeted the S2 subunit of the S protein. The results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.

/pdf/cross-reactive-serum-and-memory-b-cell-responses-to-spike-21r2kmsbdy.pdf

Cross-reactive serum and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

The emergence and fast global spread of COVID-19 has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. Africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. We also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83-3.33). A vaccine with 70% efficacy had the capacity to contain COVID-19 outbreak but at very higher vaccination coverage 94.44% (95% Crl 92.44-99.92%) with a vaccine of 100% efficacy requiring 66.10% (95% Crl 64.72-69.95%) coverage. Social distancing measures put in place have so far reduced the number of social contacts by 80.31% (95% Crl 79.76-80.85%). These findings suggest that a highly efficacious vaccine would have been required to contain COVID-19 in South Africa. Therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics.

/pdf/quantifying-early-covid-19-outbreak-transmission-in-south-3cwdartwot.pdf

Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios.

BACKGROUND: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. METHODS: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. RESULTS: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI;56.0-68.1) for bioMerieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3% (78.1-96.1), and 96.8% (86.8-99.3) for Siemens, bioMerieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC < 0.76). CONCLUSIONS: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.

Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of patients with mild COVID-19: clinical sensitivity, specificity and association with virus neutralization test.

There is limited data on the HPV immunization status of Latino/Hispanic youth in the USA. In Los Angeles County in 2015, 54,973 (34.3%) college students were of Latino/Hispanic background. We exami...

https://tandfonline.com/doi/pdf/10.1080/21645515.2019.1627819

A significant portion of college students are not aware of HPV disease and HPV vaccine recommendations

The thymus is a largely neglected organ but plays a significant role in the regulation of adaptive immune responses. The effect of aging on the thymus and immune senescence is well established, and the resulting inflammaging is found to be implicated in the development of many chronic diseases including atherosclerosis, hypertension and type 2 diabetes. Both aging and diseases of inflammaging are associated with severe COVID-19 disease, and a dysfunctional thymus may be a predisposing factor. In addition, insults on the thymus during childhood may lead to abnormal thymic function and may explain severe COVID-19 disease among younger individuals; therefore, measurement of thymic function may assist COVID-19 care. Those with poor thymic function may be treated prophylactically with convalescent serum or recombinant antibodies, and they may respond better to high-dose or adjuvanted COVID-19 vaccines. Treatments inducing thymic regeneration may improve patients' overall health and may be incorporated in COVID-19 management.

https://www.tandfonline.com/doi/pdf/10.1080/21645515.2020.1818519

The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization.

The interleukin (IL)-1 system plays a major role in immune responses and inflammation. The IL-1 system components include IL-1α, IL-1β, IL-1 receptor type 1 and IL-1 receptor type 2 (decoy receptor), IL-1 receptor accessory protein, and IL-1 receptor antagonist (IL-1Ra). These components have been shown to play a role in pregnancy, specifically in embryo-maternal communication for implantation, placenta development, and protection against infections. As gestation advances, maternal tissues experience increasing fetal demand and physical stress and IL-1β is induced. Dependent on the levels of IL-1Ra, which regulates IL-1β activity, a pro-inflammatory response may or may not occur. If there is an inflammatory response, prostaglandins are synthesized that may lead to myometrial contractions and the initiation of labor. Many studies have examined the role of the IL-1 system in pregnancy by independently measuring plasma, cervical, and amniotic fluid IL-1β or IL-1Ra levels. Other studies have tested for polymorphisms in IL-1β and IL-1Ra genes in women experiencing pregnancy complications such as early pregnancy loss, in vitro fertilization failure, pre-eclampsia and preterm delivery. Data from those studies suggest a definite role for the IL-1 system in successful pregnancy outcomes. However, as anticipated, the results varied among different experimental models, ethnicities, and disease states. Here, we review the current literature and propose that measurement of IL-1Ra in relation to IL-1 may be useful in predicting the risk of poor pregnancy outcomes.Summary SentenceThe IL-1 system has been shown to have an important role in pregnancy, and an IL-1 system assay may be used as a method to screen for women who are more likely to have a high-risk pregnancy and pregnancy complications.

The role of the IL-1 system in pregnancy and the use of IL-1 system markers to identify women at risk for pregnancy complications†

The novel coronavirus SARS-CoV-2 emerged in China in 2019 and quickly spread globally, causing a pandemic. There is an urgent need to develop vaccines against the virus, and both convalescent plasma and immune globulin are currently in clinical trials for treatment of patients with COVID-19. It is unclear whether antibodies induced by SARS-CoV-2 have neutralizing capacity and whether they can protect from future infection. Seasonal human coronaviruses (HCoV) have been circulating for decades. It is currently unknown whether antibodies against seasonal HCoV may cross-neutralize SARS-CoV-2. Data from neonates suggest that trans-placental antibodies against HCoV may have neutralizing capacity. Here we briefly review the epidemiologic observations on HCoV and discuss the potential implications for neutralizing and cross-neutralizing antibodies against SARS-CoV-2.

https://www.tandfonline.com/doi/pdf/10.1080/21645515.2020.1787074

Neutralizing and cross-reacting antibodies: implications for immunotherapy and SARS-CoV-2 vaccine development.

Purpose: This study was conducted to characterize the vaccination practices and challenges of family medicine physicians in Los Angeles County, California.Methods: The Los Angeles Academy of Family...

https://www.tandfonline.com/doi/pdf/10.1080/21645515.2018.1543524

Caitlyn Kellogg

Papers

A significant portion of college students are not aware of HPV disease and HPV vaccine recommendations

The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization.

The role of the IL-1 system in pregnancy and the use of IL-1 system markers to identify women at risk for pregnancy complications†

Neutralizing and cross-reacting antibodies: implications for immunotherapy and SARS-CoV-2 vaccine development.

Logistical and structural challenges are the major obstacles for family medicine physicians' ability to administer adult vaccines.