Colostrum Antibodies and Cytokines in Puerperal Women with Diabetes Before and During the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: Breastfeeding maintains the maternal-fetal immune link after birth, favors the transmission of immunological competence, and is considered an important contributing factor to the development of the babies' immune system. OBJECTIVE: This study aimed to obtain data related to the effects of gestational diabetes on immunoglobulin A (IgA) and cytokines levels in the colostrum, before and during the pandemic of the new coronavirus, in order to study the possible outcomes regarding the immunological characteristics of human milk. METHODS: This systematic review was registered in PROSPERO CRD42020212397, and the question elaborated using the PICO strategy was: does maternal hyperglycemia associated or not with Covid-19 influence the immunological composition of colostrum? Electronic searching and reference lists of published reports were used to identify studies that reported the influence of gestational diabetes on colostrum and milk composition. RESULTS: Seven studies were selected from the 51 found, six of them were cross-sectional and one was a case report. Six studies included Brazilian groups and only one was conducted in USA. The mothers with gestational diabetes presented a reduced level of IgA and other immunoreactive proteins in colostrum. Those alterations could be related to changes in macronutrient metabolism and cellular oxidative metabolism. CONCLUSION: It was possible to conclude that diabetes changes the immunological composition of breast milk; however, data on the impact of the association between gestational diabetes and Covid-19 infection on the composition of antibodies and cytokines present in human milk are still scarce and inconclusive.

SARS coronavirus 2-reactive antibodies in bovine colostrum.

Objective: To determine if bovine colostrum and sera have antibodies that react with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Animals: Dairy and beef cattle from North America and Europe, sampled before and after the SARS-CoV-2 pandemic. Procedures: Indirect ELISAs using whole bovine coronavirus (BCoV) and SARS-CoV-2; whole SARS-CoV-2 Spike 1, Spike 2, and nucleocapsid proteins; and SARS-CoV-2-specific nucleocapsid peptide as antigens. Virus neutralization assay for BCoV. Surrogate virus neutralization assay for SARS-CoV-2. Results: Antibodies reactive to BCoV were highly prevalent in samples collected from cattle before and after the SARS-CoV-2 pandemic. Antibodies reactive with SARS-CoV-2 were present in the same samples, and apparently increased in prevalence after the SARS-CoV-2 pandemic. These antibodies had variable reactivity with the spike and nucleocapsid proteins of SARS-CoV-2 but were apparently not specific for SARS-CoV-2. Conclusions: Bovine coronavirus continues to be endemic in cattle populations, as indicated by the high prevalence of antibodies to the virus in colostrum and serum samples. Also, the prevalent antibodies to SARS-CoV-2 in bovine samples, before and after the pandemic, are likely the result of responses to epitopes on the spike and nucleocapsid proteins that are shared between the 2 betacoronaviruses. Cross-reactive antibodies in bovine colostrum could be examined for prophylactic or therapeutic effects on SARS-CoV-2 infections in humans.

Anticorps réactifs au coronavirus du SRAS 2 dans le colostrum bovin. Objectif: Déterminer si le colostrum et des échantillons de sérum bovins contiennent des anticorps qui réagissent avec le coronavirus 2 du syndrome respiratoire aigu sévère (SRAS-CoV-2). Animaux: Bovins laitiers et bovins de boucherie d'Amérique du Nord et d'Europe, échantillonnés avant et après la pandémie de SARS-CoV-2. Procédures: Épreuves ELISA indirectes utilisant le coronavirus bovin entier (BCoV) et le SARS-CoV-2; ensemble des protéines SARS-CoV-2 Spicule 1, Spicule 2 et nucléocapside; et le peptide de nucléocapside spécifique du SARS-CoV-2 comme antigènes. Test de neutralisation du virus pour le BCoV. Virus de substitution pour le test de neutralisation du SRAS-CoV-2. Résultats: Les anticorps réactifs au BCoV étaient très répandus dans les échantillons prélevés sur les bovins avant et après la pandémie de SRAS-CoV-2. Des anticorps réactifs au SRAS-CoV-2 étaient présents dans les mêmes échantillons et leur prévalence a apparemment augmenté après la pandémie de SRAS-CoV-2. Ces anticorps avaient une réactivité variable avec les protéines de spicule et de nucléocapside du SARS-CoV-2 mais n'étaient apparemment pas spécifiques du SARS-CoV-2. Conclusion: Le coronavirus bovin continue d'être endémique dans les populations bovines, comme l'indique la forte prévalence d'anticorps dirigés contre le virus dans les échantillons de colostrum et de sérum. De plus, les anticorps prévalents contre le SRAS-CoV-2 dans les échantillons de bovins, avant et après la pandémie, sont probablement le résultat de réponses à des épitopes sur les protéines de spicule et de nucléocapside qui sont partagées entre les 2 bêtacoronavirus. Les anticorps à réaction croisée dans le colostrum bovin pourraient être examinés pour leurs effets prophylactiques ou thérapeutiques sur les infections par le SRAS-CoV-2 chez l'humain.(Traduit par Dr Serge Messier).

Impact of the Presence Anti-SARS-CoV-2 IgA in the Colostrum of Women Infected by COVID-19 During the Pregnancy in Neonatal Clinical Outcomes: A Cross-Sectional Study.

OBJECTIVES: To describe the presence of anti-SARS-CoV-2 IgA and IgG in the blood and colostrum of women with COVID-19 infection during pregnancy and associate the presence of anti-SARS-CoV-2 IgA in colostrum with clinical symptoms of their newborns. METHODS: A cross-sectional study was developed with 165 participants with COVID-19 infection during pregnancy and their newborns. DATA COLLECTED: characteristics COVID-19 infection in pregnant women, gestational age, and clinical symptoms in their newborns (fever, hypothermia, respiratory distress, hypotonia, hypoactivity, hypoglycemia, cyanosis, vomiting/regurgitation, abdominal distention, and jaundice). Maternal blood and colostrum samples were collected postpartum to to detect the presence of IgA and IgG anti-SARS-CoV-2. RESULTS: The median interval between COVID-19 diagnosis and delivery was 37.5 days (IQ = 12.0, 73.0 days). Clinical symptoms during hospitalization were observed in 55 newborns (33.3%), and two (1.6%) tested RT-PCR positive for COVID-19. Positive colostrum for anti-SARS-CoV-2 IgA was found in 117 (70.9%) women. The presence of anti-SARS-CoV-2 IgA in colostrum was associated independently with lower clinical symptoms in their newborns (OR = 0.42; 95% CI 0.202 to 0.84; p = 0.015). CONCLUSIONS FOR PRACTICE: The presence of anti-SARS-CoV-2 IgA in colostrum was detected in more than two-thirds of the women evaluated and was associated with a lower frequency of clinical symptoms in their newborns.

Comparison of the levels of selected specific antibodies in the immunoglobulin G of colostrum versus milk and serum in dairy cows (Bos taurus).

Commercial products containing immunoglobulin G (IgG) sourced from colostrum, milk, and/or serum may be used to supplement or replace maternal colostrum in newborn dairy calves. To determine if antibody specificities in bovine milk and serum IgG differ from colostrum IgG, we sampled serum, colostrum (1 to 2 hours post-partum), and milk (day 5 post-partum) from 24 dairy heifers or cows. Specific antibodies [IgG class (H&L)] to 8 common pathogens were measured using enzyme-linked immunosorbent assays (ELISAs). Immunoglobin G1 and IgG2 subclass-specific ELISAs were performed for 3 of these pathogens. Colostrum-derived IgG contained more specific antibodies to rotavirus [IgG (H&L) and IgG1] and to IgG (H&L) of bovine respiratory syncytial virus (BRSV), bovine parainfluenza-3 virus (BPI3V), Staphylococcus aureus, Escherichia coli F5 (K99), and bovine coronavirus than milk IgG. Colostral IgG contained more antibodies to BRSV (IgG1), rotavirus (IgG1), and IgG (H&L) specific for BRSV, bovine herpesvirus-1 (BHV-1), BPI3V, E. coli F5 (K99), and Streptococcus uberis than serum IgG. Compared to serum, milk contained more IgG (H&L) antibody to BRSV, BHV-1, and BPI3V, IgG1-specific BRSV, and rotavirus. These data indicate that IgG derived from colostrum delivers more specific antibodies to these endemic pathogens of calves compared to IgG sourced from milk or serum. In addition, the IgG1 subclass predominates in milk and colostrum, and both deliver a similar spectrum of antibodies.

Les produits commerciaux contenant de l'immunoglobuline G (IgG) provenant du colostrum, du lait et/ou du sérum peuvent être utilisés pour compléter ou remplacer le colostrum maternel chez les veaux laitiers nouveau-nés. Pour déterminer si les spécificités des anticorps dans le lait de vache et les IgG sériques diffèrent des IgG du colostrum, nous avons prélevé du sérum, du colostrum (1 à 2 heures après le vêlage) et du lait (5 jours après le vêlage) de 24 génisses ou vaches laitières. Des anticorps spécifiques [classe IgG (H&L)] dirigés contre huit agents pathogènes courants ont été mesurés par dosages immuno-enzymatiques (ELISA). Des tests ELISA spécifiques aux sous-classes d'IG1 et d'IgG2 ont été effectués pour trois de ces agents pathogènes. Les IgG dérivées du colostrum contenaient plus d'anticorps spécifiques contre le rotavirus [IgG (H&L) et IgG1] et des IgG (H&L) contre le virus respiratoire syncytial bovin (BRSV), le virus parainfluenza bovin 3 (BPI3V), Staphylococcus aureus, Escherichia coli F5 (K99) et le coronavirus bovin que les IgG du lait. Les IgG du colostrum contenaient plus d'anticorps dirigés contre le BRSV (IgG1), le rotavirus (IgG1) et des IgG (H&L) spécifiques contre BRSV, l'herpèsvirus bovin-1 (BHV-1), le BPI3V, E. coli F5 (K99) et Streptococcus uberis que les IgG du sérum. Comparé au sérum, le lait contenait plus d'anticorps IgG (H&L) contre le BRSV, le BHV-1 et le BPI3V, des IgG1 spécifiques au BRSV et au rotavirus. Ces données indiquent que les IgG dérivées du colostrum fournissent des anticorps plus spécifiques contre ces agents pathogènes endémiques des veaux que les IgG provenant du lait ou du sérum. De plus, la sous-classe IgG1 prédomine dans le lait et le colostrum, et les deux fournissent un spectre similaire d'anticorps.(Traduit par Docteur Serge Messier).

The impact on colostrum oxidative stress, cytokines, and immune cells composition after SARS-CoV-2 infection during pregnancy.

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19). Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum. Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H2O2, MPO) and for IL-1ß, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-ß, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum. Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H2O2, IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3-CD56brightCD16-CD27+IFN-γ+ and CD3-CD56dimCD16+CD27- were also increased. Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness.

Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.

The contribution of bovines to human health against viral infections.

In the last 40 years, novel viruses have evolved at a much faster pace than other pathogens. Viral diseases pose a significant threat to public health around the world. Bovines have a longstanding history of significant contributions to human nutrition, agricultural, industrial purposes, medical research, drug and vaccine development, and livelihood. The life cycle, genomic structures, viral proteins, and pathophysiology of bovine viruses studied in vitro paved the way for understanding the human counterparts. Calf model has been used for testing vaccines against RSV, papillomavirus vaccines and anti-HCV agents were principally developed after using the BPV and BVDV model, respectively. Some bovine viruses-based vaccines (BPIV-3 and bovine rotaviruses) were successfully developed, clinically tried, and commercially produced. Cows, immunized with HIV envelope glycoprotein, produced effective broadly neutralizing antibodies in their serum and colostrum against HIV. Here, we have summarized a few examples of human viral infections for which the use of bovines has contributed to the acquisition of new knowledge to improve human health against viral infections covering the convergence between some human and bovine viruses and using bovines as disease models. Additionally, the production of vaccines and drugs, bovine-based products were covered, and the precautions in dealing with bovines and bovine-based materials.

Proteomic Analysis of Human Milk Reveals Nutritional and Immune Benefits in the Colostrum from Mothers with COVID-19.

Despite the well-known benefits of breastfeeding and the World Health Organization's breastfeeding recommendations for COVID-19 infected mothers, whether these mothers should be encouraged to breastfeed is under debate due to concern about the risk of virus transmission and lack of evidence of breastmilk's protective effects against the virus. Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

A Novel Pathway for Porcine Epidemic Diarrhea Virus Transmission from Sows to Neonatal Piglets Mediated by Colostrum.

The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3+ T cells in the colostrum play an important role in this process. The results showed that PEDV colonizing the intestinal epithelial cells (IECs) of orally immunized infected sows could be transferred to CD3+ T cells located just beneath the IECs. Next, PEDV-carrying CD3+ T cells, with the expression of integrin α4ß7 and CCR10, migrate from the intestine to the mammary gland through blood circulation. Arriving in the mammary gland, PEDV-carrying CD3+ T cells could be transported across mammary epithelial cells (MECs) into the lumen (colostrum), as illustrated by an autotransfusion assay and an MECs/T coculture system. The PEDV-carrying CD3+ T cells in colostrum could be interspersed between IECs of neonatal piglets, causing intestinal infection via cell-to-cell contact. Our study demonstrates for the first time that colostrum-derived CD3+ T cells comprise a potential route for the vertical transmission of PEDV. IMPORTANCE The colostrum represents an important infection route for many viruses. Here, we demonstrate the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sows to neonatal piglets via colostrum. PEDV colonizing the intestinal epithelial cells could transfer the virus to CD3+ T cells located in the sow intestine. The PEDV-carrying CD3+ T cells in the sow intestine, with the expression of integrin α4ß7 and CCR10, arrive at the mammary gland through blood circulation and are transported across mammary epithelial cells into the lumen, finally leading to intestinal infection via cell-to-cell contact in neonatal piglets. Our study not only demonstrates an alternative route of PEDV infection but also provides an animal model of vertical transmission of human infectious disease.

Impact of prepartum administration of a vaccine against infectious calf diarrhea on nonspecific colostral immunoglobulin concentrations of dairy cows.

Passive transfer of colostral immunoglobulins from the cow to the calf is essential for calf health. The objective of this study was to determine if prepartum administration of a vaccine stimulates increased concentrations of colostral immunoglobulins of dairy cows beyond what is explained by vaccine-specific immunoglobulins. A prospective cohort study was conducted on a spring-calving commercial dairy farm that had a policy of only vaccinating cows with even ear tag numbers with a calf diarrhea vaccine, whereas cows with odd ear tag numbers were left unvaccinated. Cows in the vaccinated group (even ear tag numbers, n = 204) received a sensitizer and booster vaccination with a vaccine against bovine rotavirus (serotypes G6 and G10), bovine coronavirus, and E. coli having the K99 pili adherence factor. A sensitizer was given because the study vaccine was different from the vaccine previously used. Cows in the control group (odd ear tag numbers, n = 194) received a 2-mL subcutaneous sterile saline solution. Both groups received two treatments at a 3-wk interval, completing the treatments approximately 2 wk prior to the planned start of calving. During the calving period, technicians separated calves from cows immediately after parturition and prior to suckling, and cows were completely milked out within 6 h of parturition. Vaccine-specific, total, and nonvaccine-specific (total minus vaccine-specific) concentrations of immunoglobulin classes A, G1, G2a, and M (IgA, IgG1, IgG2a, and IgM, respectively) were quantified by mass spectrometry for 20 colostrum samples from each treatment group. Predicted mean non-vaccine-specific colostral IgM concentrations were 8.76 (95% CI = 7.18-10.67) and 5.78 (95% CI = 4.74-7.05) mg/mL for vaccinated and control cows, respectively (P = 0.005). Predicted mean non-vaccine-specific colostral IgG1 concentrations were 106.08 (95% CI = 92.07-120.08) and 95.30 (95% CI = 81.30-109.31) mg/mL among vaccinated and control cows, respectively; however, these means were not significantly different (P = 0.278). It is thus possible that the vaccine, in addition to specifically managing infectious calf diarrhea, may also have non-specific benefits by improving colostrum quality through increased non-vaccine-specific colostrum IgM concentrations. Further research is necessary to determine the mechanism for these preliminary findings, whether the effect may occur in other immunoglobulin classes, and what impacts it may have on calf health outcomes.

Unlike human babies, calves do not receive protective immune proteins (immunoglobulins) from the mother before birth, so a sufficient volume of immunoglobulin-rich colostrum of adequate quality must be consumed within hours of birth. It can be a challenge to meet this requirement for all dairy calves. Prior to calving, cows can be vaccinated with a vaccine against specific infectious causes of calf diarrhea to stimulate elevated concentrations of specific immunoglobulins in their colostrum, which is consumed by their calves to protect them until their own immune systems develop. We enrolled cows that were either vaccinated or not with a calf diarrhea vaccine and, using novel laboratory techniques, measured concentrations of immunoglobulin classes A, G, and M in their colostrum. As expected, vaccinated cows had elevated concentrations of vaccine-specific immunoglobulins in their colostrum. However, they also had elevated non-vaccine-specific concentrations of immunoglobulin M. The vaccine may therefore have stimulated a nonspecific increase in colostral immunoglobulin M concentrations. Further research is necessary to confirm the preliminary findings of the present study and determine the mechanism for this apparent nonspecific increase in colostral immunoglobulin M concentrations, whether it may occur in other immunoglobulin classes, and whether it may benefit calf health and growth.

Cluster randomised, controlled, triple-blind trial assessing the efficacy of intranasally administered virus-neutralising bovine colostrum supplement in preventing SARS-CoV-2 infection in household contacts of SARS-CoV-2-positive individuals: a study protocol.

The SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. BioBlock is a nasal spray of anti-SARS-CoV-2 preparation based on virus-neutralising antibodies prepared from colostrum from cows immunised with SARS-CoV-2 spike protein. This triple-blind placebo-controlled cluster randomised parallel trial seeks to evaluate the efficacy of a BioBlock spray in the prevention and treatment of SARS-CoV-2 infection. Laboratory-confirmed COVID-19 cases and their household members will be randomly allocated to each of either the intervention (BioBlock nasal spray) or the placebo (nasal spray) arms. The intervention is a 14-day course of nasal spray used by index case and household contacts. In most countries, those with confirmed or suspected infections are requisitioned to isolate at home, putting other members of their household at risk of infection. Therefore, in parallel to the need of household transmission prevention measures, households also present as a good model for infection transmission studies, allowing for the testing of several close contact transmission prevention study hypotheses. Our hope is that if the trial results are encouraging, this will provide new and additional COVID-19 prevention strategies. TRIAL REGISTRATION: ISRCTN48554326 Registered on June 14, 2021.

Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2.

Objective: To evaluate the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in colostrum from women who tested positive for the virus. Methods: Between March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Four of 15 women provided liquid colostrum, which was used for validating results obtained from spot cards. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre-coronavirus disease 2019 (COVID-19) controls. All samples were tested for reactivity to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein using an enzyme-linked immunosorbent assay that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM and for levels of 10 inflammatory cytokines (interferon-gamma [IFN-γ], tumor necrosis factor-alpha, interleukin [IL]-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13) using a multiplex electrochemiluminescent sandwich assay. Results: Our validation studies indicate that the levels of SARS-CoV-2-specific antibodies and the associated cytokines measured in liquid colostrum are comparable to levels eluted from spot cards. Bilateral colostrum samples from 73%, 73%, and 33% of the 15 COVID-19 mothers exhibited IgA, IgG, and IgM reactivity to RBD, respectively. In addition, symptomatic COVID-19 mothers had statistically significant elevated levels of 4 of the 10 inflammatory markers (IFN-γ, IL-4, IL-6, and IL-12) compared to asymptomatic COVID-19 mothers. Conclusions: A strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

Augmented antiviral T cell immunity by oral administration of IMM-124E in preclinical models and a phase I/IIa clinical trial: A method for the prevention and treatment of COVID-19.

Biological adjuvants that target the gut immune system are being developed for modulating the immune system. Hyperimmune bovine colostrum (HBC), produced by harvesting the bovine colostrum of dairy cows immunized to exogenous antigens, has been shown to modulate the immune responses and alleviate immune-mediated organ damages. The aim of the present study was to determine the ability of HBC to promote antiviral interferonγ (IFNγ) T cell responses. In a preclinical study, mice were orally administered with HBC for 5 days and tested for the number of T cell clones secreting IFNγ in response to viral antigens of the swine flu, New Caledonia influenza, and cytomegalovirus. In a phase I/IIa clinical trial, five healthy volunteers were treated for 5 days with HBC followed by testing the anti-coronavirus disease (COVID-19) immunity. In the preclinical study, oral administration of HBC augmented the number of T cell clones secreting IFNγ in response to viral antigens. In the clinical trial, oral administration of HBC to healthy males significantly increased the number of anti-COVID-19 spike protein IFNγ positive T cell clones. Oral administration of HBC provides a novel method for augmenting antiviral responses. Its high-safety profile makes it ideal for all disease stages and for pre-emptive therapy among medical personnel and other workers who are at a high risk of exposure to infections. The relatively low cost of HBC is expected to minimize care provider burdens, costs, and enable its global application.

Breastfeeding and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of contagion and the consequences of the pandemic have raised concerns among future mothers or in those who are already breastfeeding due to the risk of possible transmission of the virus through breast milk, although active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been detected in breast milk. The fear of contagion has favored mother-child isolation policies. So far, there is no evidence of vertical transmission, and the risk of horizontal transmission in the infant is similar to that of the general population. In infants with COVID-19, breastfeeding can even favorably change the clinical course of the disease.

La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Development of a rapid immunochromatographic strip test for the detection of porcine epidemic diarrhea virus specific SIgA in colostrum.

Porcine epidemic diarrhea virus (PEDV) causes very high mortality in newborn piglets. The mucosal immune system in the gut must eliminate potential pathogens while maintaining a mutually beneficial relationship with the commensal microbiota. Antibodies derived from the secretory immunoglobulin A (SIgA) class, act as the first line of antigen-specific immunity in the gut by recognizing both pathogens and commensals. Therefore, the measurement of SIgA levels is an important index in evaluating PEDV infections and immune status. A simple and rapid method for the detection of PEDV-specific SIgA using an immunochromatographic test strip has been developed; incorporating a colloidal gold-labeled anti-SIgA secretory component (SC) mAb probe for the detection of anti-PEDV-specific SIgA in swine. On the strip, a gold-labeled anti-SIgA SC mAb was applied to a conjugate pad; purified PEDV particles and goat anti-mouse antibodies were blotted onto a nitrocellulose membrane to form the test and control lines, respectively. Results showed that the immunochromatographic test strip had high sensitivity and specificity. When compared with enzyme-linked immunosorbent assay, kappa value suggesting that the strip could be used to detect PEDV specific SIgA in colostrum samples. Furthermore, the strip assay is rapid and easy to perform with no requirement for professional-level skills or equipment. We found that the immunochromatographic test strip was a rapid, sensitive, and reliable method for the identification of PEDV specific SIgA, indicating its suitability for epidemiological surveillance as well as vaccine immunity when studying PEDV.

Can Drinking Microfiltered Raw Immune Milk From Cows Immunized Against SARS-CoV-2 Provide Short-Term Protection Against COVID-19?

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Currently, several vaccine candidates against SARS-CoV-2 are in clinical trials but approval of these vaccines is likely to take a long time before they are available for public use. In a previous report, the importance of passive immunity and how immunoglobulin (Ig)G collected from recovered coronavirus patients could help in the protection against COVID-19 and boost the immune system of new patients was reported. Passive immunity by immunoglobulin transfer is a concept employed by most mammals and bovine IgG has a role to play in human therapy. IgG is one of the major components of the immunological activity found in cow's milk and colostrum. Heterologous transfer of passive immunity associated with the consumption of bovine immune milk by humans has been investigated for decades for its immunological activity against infections. This short review focuses on passive immunity and how microfiltered raw immune milk or colostrum collected from cows vaccinated against SARS-CoV-2 could provide short-term protection against SARS-CoV-2 infection in humans and could be used as an option until a vaccine becomes commercially available.

Sequential exposure to bovine viral diarrhea virus and bovine coronavirus results in increased respiratory disease lesions: clinical, immunologic, pathologic, and immunohistochemical findings.

Bovine coronaviruses (BoCVs) have been found in respiratory tissues in cattle and frequently associated with bovine respiratory disease (BRD); however, pathogenesis studies in calves are limited. To characterize the pathogenesis and pathogenicity of BoCV isolates, we used 5 different BoCV strains to inoculate colostrum-deprived calves, ~ 2-5 wk of age. Later, to determine if dual viral infection would potentiate pathogenicity of BoCV, calves were inoculated with BoCV alone, bovine viral diarrhea virus (BVDV) alone, or a series of dual-infection (BVDV-BoCV) schemes. A negative control group was included in all studies. Clinical signs and body temperature were monitored during the study and samples collected for lymphocyte counts, virus isolation, and serology. During autopsy, gross lesions were recorded and fixed tissues collected for histopathology and immunohistochemistry; fresh tissues were collected for virus isolation. Results suggest increased pathogenicity for isolate BoCV OK 1776. Increased body temperature was found in all virus-inoculated groups. Lung lesions were present in calves in all dual-infection groups; however, lesions were most pronounced in calves inoculated with BVDV followed by BoCV inoculation 6 d later. Lung lesions were consistent with mild-to-moderate interstitial pneumonia, and immunohistochemistry confirmed the presence of BoCV antigen. Our studies demonstrated that BVDV-BoCV dual infection may play an important role in BRD pathogenesis, and timing between infections seems critical to the severity of lesions.