Absence of blood donors' anti-SARS-CoV-2 antibodies in pre-storage leukoreduced red blood cell units indicates no role of passive immunity for blood recipients.

Transfer of vaccine antibodies (Ab) from donors to recipients after transfusion of packed red blood cells (RBC) is supposed, thus affecting the recipients' response to vaccinations. In this prospective study, SARS-CoV-2 IgG level in donors' serum and RBC supernatant samples was assessed. Among 346 subjects, 280 were referred for hyperimmune plasma donation and 30 for whole blood donations. All units underwent pre-storage filtration, and residual plasma volume was 18±18 mL. The mean total IgG and IgM levels were 171.43 ± 48.79 and 11.43 ± 10.69 mg/dL respectively, with significant reduction after plasma depletion and filtration (IgG 5.86 ± 5.2 and IgM 1.43 ± 3.78, p < 0.05). Anti-COVID-19 Ab were identified in serum of 28/30 (93.5%) blood donors but were absent in all blood units. The mean value of anti-SARS-CoV-2 IgG level in donors' serum samples and in RBC units was 8.80 S/C (range 0.01-23.4) and 0.11 (range 0.01-0.37) S/C, respectively (p<0.05). This study shows deplasmation and leukodepletion of RBC units ensured removal of IgG content and no red blood cell unit was reactive for anti-COVID-19 antibodies even from donors with high serum titre. These findings demonstrate that deplasmated and leukodepleted RBCs are not to be considered blood products containing substantial amounts of immune globulin, and differently from other blood derived-products containing Ab, transfusions with deplasmated and leukodepleted RBCs do not require delayed vaccinations and a revision of current recommendations is requested.

Rapid development and mass production of SARS-CoV-2 neutralizing chicken egg yolk antibodies with protective efficacy in hamsters.

Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.

Condition of surplus dairy calves during marketing: A cross-sectional study.

In North America, surplus dairy calves are sold soon after birth and often marketed through a third party (e.g., live auction, livestock dealer) before entering veal or dairy beef production. Previous work has demonstrated that a percentage of calves have failed transfer of passive immunity (FTPI) and clinical signs of disease on arrival at calf-raising facilities, but little is known regarding calf condition during marketing. The objectives of this cross-sectional study were to (1) estimate the prevalence of FTPI and poor health outcomes in surplus calves on arrival at livestock dealers, and (2) investigate the association between calf-level variables (body weight, sex, source) and health outcomes. Two livestock dealers in Ohio were visited 2 to 3 times per week, with approximately 28 calves enrolled in the study per visit for a total of 1,119 calves. One blood sample per calf was obtained to evaluate FTPI by measuring serum total protein concentrations (using a cutoff <5.1 g/dL). Calves were clinically evaluated for signs of arthritis, broken ribs or tail, dehydration, depression, diarrhea, fever, navel inflammation, and respiratory disease by 2 observers; health outcomes were dichotomized using clinically relevant cut points. Descriptive statistics were used to estimate the prevalence of calves with poor health outcomes. Multivariable logistic regression models were built to investigate the effect of body weight, sex, and source on health outcomes. Nineteen percent (206/1,091) of calves had FTPI.

Associations of serostatus upon arrival with clinical respiratory disease, lung consolidation, and growth in veal calves.

Respiratory tract infections remain a major problem during calf rearing, especially among milk (formula)-fed veal. Preconditioning of calves through appropriate colostrum management and vaccination could be helpful to address this issue. The objective of this study was to investigate whether the presence of serum antibodies against major respiratory tract pathogens (bovine respiratory syncytial virus, parainfluenza 3 virus, bovine coronavirus, Mycoplasmopsis bovis, Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica) and total serum IgG concentration in calves upon arrival at the veal facility were associated with the occurrence of clinical bovine respiratory disease (BRD) or lung consolidation in the first 3 wk, as assessed by both the Wisconsin BRD scorecard (based on 5 clinical signs: cough, rectal temperature, ear position, and nasal and ocular discharge) and by quick thoracic ultrasound scanning. Additionally, the association between calves' serostatus production parameters were explored. A prospective cohort study was conducted among 442 male dairy calves on a large veal calf facility in Belgium. Both clinical scoring and quick thoracic ultrasound scanning were performed on all calves at 4 key moments in the production cycle: arrival at the facility, initiation of first metaphylactic antimicrobial treatment at peak incidence of BRD (wk 1), end of the first metaphylactic treatment (short-term evaluation) and at wk 10 (long-term evaluation). Mixed effects logit regression models were fitted to quantify relationships. The outcomes of interest were clinical respiratory disease (Wisconsin BRD scorecard positive), lung consolidation (≥1 cm or ≥ 3 cm), average daily weight gain, and cold carcass weight. In the first week of production, incidence of lung consolidation (≥1 cm) quickly increased from 14.9% upon arrival to 43.0% at the peak of the BRD incidence, while clinical BRD increased from 3.6% to 16.1%. The main finding of this study was that calves who were seropositive for bovine respiratory syncytial virus and bovine coronavirus at arrival had reduced odds of developing lung consolidation at the peak of the outbreak, 0.58 odds ratio (95% CI: 0.38-0.89) and 0.37 odds ratio (95% CI: 0.20-0.69), respectively. No relationships between serum IgG concentration at arrival and the development of lung consolidations or clinical respiratory disease were found. Nevertheless, on average, throughout the first 10 wk of the fattening cycle, calves with failed transfer of passive immunity (serum IgG < 7.5 g/L) gained 40 g/d (95% CI: 10-70 g/d) less weight (average daily gain). Hence, ensuring that calves have a positive serostatus for these respiratory tract pathogens before entering the facility may help lower the incidence of lung consolidations, subsequently reducing treatment incidence and the adverse effects on primary economic outcomes.

Association of morbidity, mortality, and average daily gain with transfer of passive immunity in dairy-beef crossbred calves up to 60 d of life.

Adequate transfer of passive immunity (TPI) is a cornerstone for a proper health status of calves. In the literature, there is limited information on the prevalence of failure of TPI in dairy-beef crossbred calves and its impact on morbidity, mortality, and average daily gain (ADG) during the preweaning period. Therefore, this study aimed to evaluate the association between TPI with morbidity, mortality, and ADG in pre-weaned dairy-beef crossbred calves. A total of 1,055 newborn dairy-beef crossbred calves were enrolled upon arrival at a calf-raising facility in California from January to August 2021. Farm of origin, genetic breed group, sex, and body weight were recorded upon arrival. Blood was collected at 24 ± 1 h post-arrival to evaluate serum IgG concentration, serum total protein (TP), and packed cell volume. Morbidity (diarrhea and respiratory treatment records) and mortality were recorded daily until 60 d of life. Calves were grouped into 2 genetic breed groups: Holstein x Beef (Ho x Be, 49.6%) and Jersey × Beef crossbred calves (Je × Be, 50.4%). Descriptive statistics and Cox proportional hazard models were created to evaluate the association of TPI categories for serum IgG (TPI-IgG: poor: < 10.0 g/L, fair: 10.0 - 17.9 g/L, good: 18.0 - 24.9 g/L, and excellent: ≥ 25.0 g/L) and TP (TPI-TP: poor: < 5.1 g/dL, fair: 5.1 - 5.7 g/dL, good: 5.8 - 6.1 g/dL, and excellent: ≥ 6.2 g/dL), sex, and genetic breed group with morbidity and mortality. Additionally, a mixed linear regression was performed to evaluate the association of sex, genetic breed group, and TPI categories with ADG. Overall morbidity and mortality were 84.8% (n = 895) and 2.5% (n = 26). Calves classified as TPI-IgG excellent were associated with the lowest (43.2% less) hazard of being treated compared with TPI-IgG poor calves. For mortality, dairy-beef crossbred calves with TPI-IgG excellent were associated with a reduction of 82.0% in the hazard of dying compared with TPI-IgG poor. The TPI-IgG poor and TPI-IgG fair calves were associated with a decreased ADG of 101.0 and 98.8 g/d, respectively, in comparison with TPI-IgG good calves. Average daily gain of TPI-IgG good and TPI-IgG excellent calves were not different. In our study, dairy-beef crossbred calves enrolled may have endured challenging conditions that increased morbidity. This reinforces the importance of high IgG levels to decrease morbidity and mortality and maximize ADG in dairy-beef crossbred calves raising systems. Further research should evaluate the long-term effects of TPI categories on the health and performance of dairy-beef crossbred calves.

Key changes in bovine milk immunoglobulin G during lactation: NeuAc sialylation is a hallmark of colostrum immunoglobulin G N-glycosylation.

We monitored longitudinal changes in bovine milk IgG in samples from four cows at 9 time points in between 0.5 and 28 days following calving. We used peptide-centric LC-MS/MS on proteolytic digests of whole bovine milk, resulting in the combined identification of 212 individual bovine milk protein sequences, with IgG making up >50 percent of the protein content of every 0.5 d colostrum sample, which reduced to ≤3 percent in mature milk. In parallel, we analyzed IgG captured from the bovine milk samples to characterize its N-glycosylation, using dedicated methods for bottom-up glycoproteomics employing product ion-triggered hybrid fragmentation; data are available via ProteomeXchange with identifier PXD037755. The bovine milk IgG N-glycosylation profile was revealed to be very heterogeneous, consisting of >40 glycoforms. Furthermore, these N-glycosylation profiles changed substantially over the period of lactation, but consistently across the four individual cows. We identified NeuAc sialylation as the key abundant characteristic of bovine colostrum IgG, significantly decreasing in the first days of lactation, and barely detectable in mature bovine milk IgG. We also report, for the first time to our knowledge, the identification of subtype IgG3 in bovine milk, alongside the better-documented IgG1 and IgG2. The detailed molecular characteristics we describe of the bovine milk IgG, and their dynamic changes during lactation, are important not only for the fundamental understanding of the calf's immune development, but also for understanding bovine milk and its bioactive components in the context of human nutrition.

Kinetics of Maternally Derived Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Infants in Relation to the Timing of Antenatal Vaccination.

BACKGROUND: SARS-CoV-2 infection during early infancy can result in severe disease. We evaluated the durability of maternally-derived anti-SARS-CoV-2 antibodies in infants and its relation to antenatal vaccination timing. METHODS: Sera were prospectively collected at birth and 3 months after delivery from mother-infant pairs following antenatal BNT162b2 vaccination. SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels and neutralizing activity were evaluated. RESULTS: 56 mother-infant pairs were included: 15 (26.8%) were vaccinated in the first trimester, 16 (28.6%) in the second trimester, and 25 (44.6%) in the third trimester.At the time of delivery, all neonates were positive for anti-RBD-specific IgG with a median concentration of 4046 [IQR 2446-7896] AU/mL, with the highest concentration found after third trimester vaccination (median 6763 [IQR 3857-12561] AU/mL). At 3 months after delivery, anti RBD-specific IgG levels in infants significantly waned with a median concentration of 545 [IQR 344-810] AU/mL (P < .001). The half-life of anti-RBD-specific IgG was 66 days among mothers and 30 days among infants. While at the time of delivery, all neonates had detectable neutralizing activity regardless of gestational age at vaccination, at 3-months of age, a higher proportion of infants born to mothers vaccinated in third trimester had persistent neutralizing activity as compared to those born to mothers vaccinated in second trimester. CONCLUSIONS: Maternal vaccination leads to efficient transplacental antibody transfer, with persistent anti-SARS-CoV-2 antibodies detected at 3 months of age in all infants. The observed effect of antenatal immunization timing on the kinetics of maternally-derived antibodies may have implications for SARS-CoV-2 vaccination strategies.

SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Show Markedly Reduced Cross-reactivities Against Omicron Variants.

PURPOSE: Patients with antibody deficiencies often receive maintenance treatment with donor plasma-derived immunoglobulin (Ig) preparations to decrease the incidence and severity of infections. We have previously shown that IgG antibodies to the original SARS-CoV-2 strain were not consistently present in off-the-shelf Ig batches produced up to approximately 18 months after the first identified case of COVID-19 in the USA and that Ig batches with anti-SARS-CoV-2 IgG primarily contained vaccine-induced spike specific antibodies. This study aimed to investigate the degree of cross-reactivity between vaccine-induced anti-SARS-CoV-2 antibodies against Wuhan strain and subsequent viral variants. METHODS: Samples were collected from 74 Ig batches supplied by three different commercial manufacturers. All batches were used at the Immunodeficiency Unit at the Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until September 2022. Antibody quantity and potential to neutralize virus entry into host cells were assessed against the original SARS-CoV-2 Wuhan strain and the following nine variants: Alpha, Beta, Delta, IHU, and the Omicron BA.1, BA.1.1, BA.1 with spike mutation L452R, BA.2, and BA.3. RESULTS: Ig batches produced approximately 18 months after the SARS-CoV-2 outbreak (from around July 2021) and later consistently contained high quantities of antibodies that bind the Wuhan strain. The Ig batches had overall low reactivity to the SARS-CoV-2 nucleocapsid, which implies that plasma donor spike IgG essentially is the result of vaccination. We assessed the degree of cross-reactivity towards each virus variant by plotting the variant/Wuhan strain ratio, which was consistent regardless of production date, suggesting cross-reactivity with vaccine-induced antibodies rather than virus exposure in the plasma donor population. Viral variants that emerged later during the pandemic systematically had a lower reactivity ratio, except for the Delta and IHU variants. The Ig batches displayed markedly low neutralizing potential towards the Beta variant and all tested Omicron variants. CONCLUSION: Commercial Ig batches currently contain large quantities of SARS-CoV-2 vaccine-induced antibodies. Cross-reactivity with variant strains is evident but varies, with markedly low neutralizing potential observed against Omicron variants.

Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice.

SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta VoC in the K18 human angiotensin converting enzyme 2 (hACE2) transgenic mouse model. HCP protected mice from challenge with the original WA-1 SARS-CoV-2 strain; however, only partially protected mice challenged with the Alpha VoC (60% survival) and failed to save Beta challenged mice from succumbing to disease. HCP treatment groups had elevated receptor binding domain (RBD) and nucleocapsid IgG titers in the serum; however, Beta VoC viral RNA burden in the lung and brain was not decreased due to HCP treatment. While mice could be protected from WA-1 or Alpha challenge with a single dose of HCP, six doses of HCP could not decrease mortality of Delta challenged mice. Overall, these data demonstrate that VoC have enhanced immune evasion and this work underscores the need for in vivo models to evaluate future emerging strains. IMPORTANCE Emerging SARS-CoV-2 VoC are posing new problems regarding vaccine and monoclonal antibody efficacy. To better understand immune evasion tactics of the VoC, we utilized passive immunization to study the effect of early-pandemic SARS-CoV-2 HCP against, Alpha, Beta, and Delta VoC. We observed that HCP from a human infected with the original SARS-CoV-2 was unable to control lethality of Alpha, Beta, or Delta VoC in the K18-hACE2 transgenic mouse model of SARS-CoV-2 infection. Our findings demonstrate that passive immunization can be used as a model to evaluate immune evasion of emerging VoC strains.

SARS-CoV-2 IgG "heritage" in newborn: A credit of maternal natural infection.

Description of transplacental passage of specific SARS-CoV-2 IgG from mothers who contracted natural infection to their newborns. Retrospective cohort analysis including pregnant women diagnosed with SARS-CoV-2 and their newborns both tested for SARS-CoV-2 specific IgG and IgM with antibody titration at delivery. Nasopharyngeal swab were taken from both mothers and neonates, and tested for SARS-CoV-2 using polymerase chain reaction (PCR). IgM and IgG were analyzed in maternal and neonatal serum of 143 mother-infant dyads. 86% of women with a positive SARS-CoV-2 PCR >14 days before delivery developed specific IgG and 84% of their infants showed transplacental passage of IgG. Pregnant women infected with SARS-CoV-2 achieve antibody seroconversion following the kinetics described in the general population, and transplacental transfer of IgG specific antibodies occurs. No conclusion can be drawn on passive immunity efficacy or duration.

Selective decline of bacteria colonizing the calf hindgut during colostrum to milk transition, with persistence of taxa correlating with host passive immunity.

In neonate calves, the association between gut microbial colonization and passive immunity acquisition remains largely unknown. We evaluated the effect of transition from colostrum to milk on the hindgut microbiota, and the correlations between acquired passive immunity and this microbiome. In 14 Holstein calves, colostrum quality and host passive immunity were measured, feces were sampled when feeding colostrum and after transition to milk. Then, in eight calves displaying a wide range of passive immunity, the hindgut microbiota was evaluated with DNA sequencing; differential abundance was analyzed with Maaslin2. With transition from colostrum to milk, many initial bacterial colonizers did not survive; genus Ralstonia decreased, but Lactobacillus and Bacteroides increased. When feeding colostrum, the amount of immunoglobulins consumed positively correlated with abundance of Lactobacillaceae and Lachnospiraceae, but Escherichia-Shigella and Clostridium sensu stricto 1 correlated negatively with host passive immunity. After transition to milk, acquired passive immunity negatively correlated with Clostridium sensu stricto 1, Ralstonia, and Veillonella. Overall, many initial hindgut colonizers did not thrive during transition from colostrum to milk, homogenizing the bacterial profile with prevalence of milk digesters. Several bacterial taxa showed strong correlation with host passive immunity, suggesting an interplay between calf passive immunity acquisition and the colonizing microbiota.

Association between transfer of passive immunity, health, and performance of female dairy calves from birth to weaning.

The objective of this observational study was to compare calf health, average daily weight gain, and calf mortality considering the proposed categories of transfer of passive immunity (TPI) by the consensus report of Lombard et al. (2020). The consensus report defines 4 categories of passive immunity (excellent, good, fair, and poor) of calves obtained after colostrum ingestion. The association between the 4 TPI categories was analyzed on calf health (i.e., hazards for morbidity and mortality), and average daily weight gain (ADG) of female Holstein Friesian calves during the first 90 d of age. A further aim of this study was to examine the effects of calving-related factors, such as dystocia or winter season, on TPI status. We hypothesized that calves with excellent TPI have greater ADG, lower risks for infectious diseases such as neonatal diarrhea, pneumonia, and omphalitis, and lower mortality rates. This observational study was conducted from December 2017 to March 2021. Blood was collected from 3,434 female Holstein Friesian dairy calves from 1 commercial dairy farm. All female calves aged 2 to 7 d were assessed for TPI status by determination of total solids (TS) in serum via Brix refractometry by the farm personnel once a week. Passive immunity was categorized according to Lombard et al. (2020) with excellent (≥9.4% Brix), good (8.9-9.3% Brix), fair (8.1-8.8% Brix), or poor TPI (<8.1% Brix). For the analysis of ADG and calving ease 492 or 35 calves had to be excluded due to missing data. The distribution of calves according to TPI categories was as follows: 4.8% poor (n = 166), 29.5% fair (n = 1,012), 28.3% good (n = 971), and 37.4% excellent (n = 1,285). From the calving-related factors, parity of the dam, calving ease, birth month, calving assistance by different farm personnel, and day of life for TPI assessment were significantly associated with TS concentration. Out of 3,434 calves, 216 (6.3%) had diarrhea, and 31 (0.9%) and 957 (27.9%) suffered from omphalitis and pneumonia during the first 90 d of life, respectively. Overall, the morbidity during the preweaning period was 32.6% (n = 1,118), and the mortality was 3.1% (n = 107). The ADG was 0.90 ± 0.15 kg with a range of 0.32 to 1.52 kg. The Cox regression model showed that calves suffering from poor TPI tended toward a greater hazard risk (HR) for diarrhea (HR = 1.57, 95% CI: 0.92-2.69) compared with calves with excellent TPI. Calves suffering from TPI had a greater HR for pneumonia (HR = 2.00, CI: 1.53-2-61), overall morbidity (HR = 1.99, CI: 1.56-2.55), and mortality (HR = 2.47, CI: 1.25-4.86) in contrast to excellent TPI. Furthermore, calves with good and fair TPI had significantly greater HR for pneumonia (good TPI: HR = 1.35, CI: 1.15-1.59; fair TPI: HR = 1.41, CI: 1.20-1.65) and overall morbidity (good TPI: HR = 1.26, CI: 1.09-1.47; fair TPI: HR = 1.32, CI: 1.14-1.53) compared with the excellent TPI category. Average daily weight gain during the first 60 d of life was associated with TPI categories. Calves with excellent and good TPI status had ADG of 0.90 ± 0.01 kg/d and 0.92 ± 0.01 kg/d (mean ± SE), respectively. The ADG of calves with fair TPI status was 0.89 ± 0.01 kg/d, and calves suffering from poor TPI had 0.86 ± 0.01 kg/d. Average daily weight gain differed in calves with poor TPI compared with the other categories. Fair and excellent TPI differed additionally from good TPI. We found no statistical difference between the TPI categories fair and excellent. In conclusion, poor TPI was associated with higher morbidity and mortality during the first 90 d of life. Furthermore, calves with fair, good or excellent TPI had greater ADG.

The effect of maternal supply of rumen-protected protein to Holstein Friesian cows during the dry period on the transfer of passive immunity and colostral microbial composition.

The objective of this study was to analyze if maternal supply of rumen-protected protein during the dry period can affect the IgG concentration and microbial composition of colostrum and the IgG absorption and fecal microbial composition in the calf. Seventy-four multiparous Holstein Friesian (HF) dairy cows were stratified per parity and randomly assigned to one of 2 different dry period diets, a diet with a low crude protein (CP) level (LP) and a diet with a high CP level (HP) by addition of rumen-undegraded protein (RUP; formaldehyde-treated soybean meal, Mervobest, Nuscience, Drongen, Belgium). Colostrum was collected within 1 h after calving and IgG concentration was quantified by radial immunodiffusion analysis. Forty-nine calves (23 female and 26 male) were enrolled in the trial with a 2 × 2 factorial design, with prenatal and postnatal treatment as the 2 independent variables. This led to 4 experimental groups: LPLP, LPHP, HPLP, and HPHP, in which the first 2 letters refer to the prenatal treatment (diet of the dam) and the last 2 refer to the postnatal treatment (diet of the colostrum-producing cow). Calves received 3× 2 L of colostrum within 2, 6, and 24 h after birth. Meconium and feces were collected solely from female calves (n = 18) by digital palpation of the rectum, immediately after birth and before colostrum administration and at d 3 of age. Microbial DNA was extracted from meconium (n = 9), feces (n = 15), and colostrum (n = 49). Amplicon sequencing of the bacterial V3-V4 region of the 16S rRNA gene was performed for characterization of the bacterial communities. Colostrum IgG concentration was higher in cows that were supplemented with RUP, especially in cows entering their second lactation (LSM ± SEM 61.3 ± 2.3 vs. 55.2 ± 2.8 g of IgG/L). Calves born out of LP cows that received colostrum from HP cows (LPHP) had a lower serum IgG level compared with HPHP and LPLP calves (LSM ± SEM 14.2 ± 1.3 vs. 18.8 ± 1.2 and 20.9 ± 1.3 g of IgG/L in HPHP and LPLP, respectively). The most abundant phyla in colostrum were Proteobacteria (48.2%), Firmicutes (24.8%), Bacteroidetes (9.5%), and Actinobacteria (5.0%). The most abundant phyla in calf meconium and feces were Firmicutes (42.5 and 47.5%), Proteobacteria (21.7% and 33.7%), Bacteroidetes (16.8% and 15.7%), and Actinobacteria (2.9% and 3.1%). There was no difference in the overall microbial communities between colostrum from HP and LP cows. However, 2 genera (both members of the family Lachnospiraceae) were more abundant in colostrum from HP cows compared with LP cows. The microbial composition of meconium, feces and colostrum differed from each other. Fecal samples were more similar to each other and are characterized by a lower intersample diversity compared with colostrum and meconium samples. To conclude, increasing the CP level by addition of RUP in the dry period diet affected the colostrum IgG concentration and the transfer of passive immunity, but did not change the overall microbial composition of colostrum nor of meconium and feces in the calf.

A meta-analysis of the effects of colostrum heat treatment on colostral viscosity, immunoglobulin G concentration, and the transfer of passive immunity in newborn dairy calves.

Newborn ruminants depend on colostrum intake immediately after birth to obtain immunoglobulins for effective transfer of passive immunity (TPI). As colostrum may also be a vehicle of infectious agents, heat treatment of raw colostrum is a practice aimed at eliminating or reducing its pathogen load. Despite the usefulness of heat treatment in preventing the transmission of infectious colostrum-borne diseases, heat treatment of colostrum may have some side effects. A systematic review and meta-analysis were conducted to summarize the effects of colostrum heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration as a proxy for TPI in newborn calves fed raw versus heat-treated colostrum. Moderators were studied to identify sources of heterogeneity. Literature databases were searched for peer-reviewed articles published between 1946 and 2022. A Master of Science thesis was also included. Five, 21, and 19 original publications were quantitatively evaluated in 3 separate meta-analyses, based on predefined selection criteria. Two-level and 3-level random-effects meta-analysis revealed a significant overall effect of heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration in newborns. Heat-treated colostrum had significantly higher viscosity (21.0 cP, 95% CI: 3.8 to 38.2) and lower IgG concentration (-7.4 g/L, 95% CI: -11.1 to -3.7) compared with raw colostrum. Overall, newborn calves fed heat-treated colostrum had higher serum IgG concentrations (2.8 g/L, 95% CI: 1.4 to 4.0) 24-48 h after birth than those fed with raw colostrum. Particularly, this positive effect on the serum IgG concentrations was seen when colostrum was heat-treated at ≤60°C (2.9 g/L, 95% CI: 0.9 to 4.2) and when the standard low-temperature low-time (LTLT) method was used for heat treatment (2.6 g/L, 95% CI: 0.1 to 5.1). Colostrum treated at >60-63.5°C tended to have higher viscosity (275.6 cP, 95% CI: -37.9 to 589.3) and had lower IgG concentration (-21.7 g/L, 95% CI: -27.3 to -16.1). Calves fed colostrum treated at this temperature range had significantly lower serum IgG (-4.2 g/L, 95% CI: -7.9 to -0.4) compared with those fed raw colostrum. Heat treatment of colostrum at 72-76°C was not associated with a significant increase in colostral viscosity (6.3 cP, 95% CI: -324.3 to 336.9) nor a reduction in IgG colostral concentration (-13.1 g/L, 95% CI: -26.5 to 0.2), but calves fed colostrum treated at this temperature range had a significant reduction in serum IgG (-11.3 g/L, 95% CI: -17.1 to -5.4). Feeding newborn calves with colostrum heat-treated at ≤60°C by the standard LTLT method, particularly within 2 h after birth, resulted in increased serum IgG concentration at 24-48 h of age. Importantly, delaying feeding of heat-treated colostrum to newborns beyond 2 h of age resulted in no significant difference in IgG serum levels compared with feeding raw colostrum, highlighting the importance of early administration of heat-treated colostrum to favor TPI. On-farm colostrum heat treating should achieve an equilibrium between pathogen elimination and the preservation of colostral immunoglobulins while minimizing undesired increases in viscosity. The beneficial effects of colostrum heat treatment on TPI can be negligible if colostrum feeding is not performed within 2 h after birth.

Condition of bob veal calves on arrival at an abattoir in Ohio.

Previous research has shown surplus dairy calves arrive at 'formula-fed' veal operations in North America in sub-optimal condition; however, little is known about the condition of 'bob' veal calves on arrival at abattoirs. The objectives of this study were to assess the condition of bob veal calves on arrival at an abattoir in Ohio and determine risk factors for poor health outcomes. On arrival, 35 calves in each of 12 cohorts (n = 420 calves) were assessed using a standardised health examination. A blood sample was also collected to assess failed transfer of passive immunity (FTPI) and hypoglycaemia. Descriptive statistics were used to describe the prevalence of poor health outcomes. Mixed-effects logistic regression models were used to identify if calf breed, sex, or source were risk factors for poor health outcomes. The most common physical health concern observed on arrival at the abattoir was dehydration (mean: 68.6%), followed by thin body condition (39.8%), and navel inflammation (25.7%). Approximately one-quarter (23.4%) of calves had FTPI and 73.4% were hypoglycaemic. Male calves were more likely than females to arrive hypoglycaemic. Hydration status was associated with breed; Jersey and crossbreed calves were less likely to be dehydrated than Holstein-Friesian calves. Buying station tended to be associated with FTPI. These results underline the need for more studies investigating morbidity, mortality, and their underlying risk factors to promote calf welfare prior to slaughter in each stage of the production chain: on the dairy farm of birth, during marketing, and in transit.

Metabolic profile of transition period in ewes and its influence on passive immunity transference in lambs.

The intensification of ewe production, focusing on increasing prolificity, results in a higher incidence of metabolic disorders, especially in the transition period, which can lead to production losses with consequences for the health of the animals. The objective of this study was to evaluate the metabolic profile in transition period Lacaune ewes according to the parity and litter size born and its influence on the transference of passive immunity. Nineteen Lacaune ewes, with initial mean body weight of 76.36 ± 10.37 kg (SD), kept in a semi-extensive system and receiving the same diet, were used. Ewes were classified according to parity (primiparous and multiparous) and the litter size born at parturition (1, 2, and 3). On days - 14, - 7, and - 4 of the expected date of parturition and on days 1, 4, 7, and 14 days postpartum, blood sampling, the evaluation of the body condition score (BCS), and the weighing of animals were performed. Blood samples were taken from the lambs 48 h after birth. Colostrum was collected up to 6 h postpartum to determine the brix percentage. Serum concentrations of total plasma proteins (TPP), albumin, aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), paraoxonase (PON1), calcium (Ca), and magnesium (Mg) were evaluated. In lambs, the blood parameters evaluated were TPP, albumin, GGT, and PON1. Lamb plasma was used to estimate colostrum efficiency, brix percentage immunity, and total plasma protein (PPT). Productive data, pre- and postpartum metabolic variables for ewes, lambs, and those related to colostrum brix were analyzed. The BCS had a reduction (p < 0.0001) in the postpartum period, which is evidenced on days 7 and 14 (2.88 and 2.73, respectively). Serum concentration of BHB presented the highest concentrations in the prepartum period for ewes that gave birth to triplets, from day - 14, and for ewes that gave birth to twins on day - 4 (p = 0.0245). Serum concentration of NEFA demonstrated the highest value on day 14 in primiparous (1.07; p = 0.0402). Calcium had the lowest concentrations on day 1 (8.85 mg/dl, p < 0.0001) and magnesium on day 3 (1.79 mg/dl, p < 0.0001) postpartum. The multiparous with two lambs had higher brix percentages (30.5%), and the lowest value was observed in primiparous ewes that gave birth to a single lamb (27.06%; p = 0.0395). Triplet lambs had the lowest weight (3.73 kg, p = 0.0007), and the best brix percentage in plasma was observed in twins (10.29%, p = 0.0174). Regardless of the parity, the ewes that presented the greatest metabolic challenge were those that gave birth to triplets, and these lambs presented the worst immunity and the lowest live weight. The quality of colostrum was influenced by the parity, and multiparous ewes that gave birth to triplets had the lowest brix percentage in the colostrum.

Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant.

Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient.

Antibodies in the breastmilk of COVID-19 recovered women.

OBJECTIVE: Human milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which may serve as a protective factor through passive immunization in infants. The objective of this study was to measure the levels of anti-SARS-CoV-2 IgG and IgA in human milk and serum after a SARS-CoV-2 infection. DESIGN: Breast milk and serum samples from 72 lactating mothers with confirmed SARS-CoV-2 asymptomatic or symptomatic infection were collected 1-229 days after the onset of clinical symptoms related to COVID-19. Seventeen mothers with no history of COVID-19 served as a control group. Enzyme-Linked ImmunoSorbent Assay was performed to analyze antibodies against SARS-CoV-2. RESULTS: SARS-CoV-2-IgA human milk antibodies were detected in mothers and their concentrations were consistently higher than SARS-CoV-2-IgG antibodies. The serum and breastmilk samples of women with COVID-19 was characterized by a higher concentration of anti-RBD IgA and IgG than the serum from the control group without COVID-19. No statistically significant difference was observed between the antibody levels in the serum samples obtained from symptomatic and asymptomatic women exposed to SARS-CoV-2 and between the antibody level and the time from a positive SARS-CoV-2 test result over the period studied. CONCLUSION: Our results confirm the presence of SARS-CoV-2 IgA and IgG antibodies in the breastmilk of COVID-19 recovered women and the possibility of these antibodies in providing specific immunologic benefits to breastfeeding infants such as protection against the virus transmission and severity of the acquired COVID-19 disease.

Effect of convalescent plasma as complementary treatment in patients with moderate COVID-19 infection.

INTRODUCTION: South America is one of the regions most affected by the COVID-19 pandemic. Specific and affordable treatments are needed to treat SARS-CoV-2 infection. Evidence regarding the use of convalescent plasma in COVID-19 patients is still limited. We compared the safety and efficacy of COVID-19-convalescent plasma administration as a complement to standard treatment in the early management of patients with moderate SARS-CoV-2 infection. METHODS: We carried out a random double blinded, placebo-controlled trial that compared standard treatment plus convalescent plasma (CP) or plus non-convalescent plasma in the management of COVID-19 patients. The main outcome was survival and secondary endpoints included: length of hospitalisation (LOH), days from treatment to discharge, time to clinical improvement or death within a 28-day period, and adverse reactions to treatment. RESULTS: Administration of CP with antibodies against SARS-CoV-2 did not affect patient survival, RR = 1.003, 95% CI (0.3938, 2.555). These results led to terminate the RCT prematurely. However, early treatment of COVID-19 patients with CP tended to decrease the LOH while the delay in CP treatment was associated with longer hospitalisation. In addition, delay in CP treatment negatively affected the recovery of the respiratory rate. CONCLUSION: Use of CP for the treatment of COVID-19 patients is safe and its early use can decrease the LOH and improve respiratory function. Early administration of antibody-rich CP could contribute to decrease the negative impact of COVID-19 pandemic in patients with impaired immune response.

Invited review: The importance of colostrum in the newborn dairy calf.

It is critical that bovine maternal colostrum is fed to newborn calves during their first hours of life. Colostrum is the secretion a cow produces after mammary involution that is rich in various nutrients. In addition to the nutritive value for newborn calves, immunoglobulins are of interest due to their role in developing the naïve immune system of calves at birth. The process by which a calf acquires immunity via absorption of immunoglobulins is defined as passive immunity. When calves consume an adequate amount of immunoglobulins, they are classified as having successful passive immunity (SPI). In contrast, if they are deprived of adequate colostrum, they are considered to have had a failure of transfer of passive immunity (FPI). Transfer of passive immunity is assessed by measuring serum IgG concentrations at 24 to 48 h of age. The major factors that influence whether a calf has SPI or FPI are colostrum IgG concentration, quantity fed, and age of calf at colostrum feeding. Monitoring apparent efficiency of immunoglobulin absorption in calves is often recommended to evaluate overall colostrum management practices. Serum IgG analyses can be determined with direct (radial immunodiffusion) or indirect (refractometry) methods and used to assess SPI or FPI prevalence.