SARS-CoV-2 Antibodies in Breast Milk After Vaccination.

BACKGROUND AND OBJECTIVES: Passive and active immunity transfer through human milk (HM) constitutes a key element in the infant's developing immunity. Certain infectious diseases and vaccines have been described to induce changes in the immune components of HM. METHODS: We conducted a prospective cohort single-institution study from February 2 to April 4, 2021. Women who reported to be breastfeeding at the time of their coronavirus disease 2019 (COVID-19) vaccination were invited to participate. Blood and milk samples were collected on day 14 after their second dose of the vaccine. Immunoglobulin G (IgG) antibodies against nucleocapsid protein as well as IgG, immunoglobulin M and immunoglobulin A (IgA) antibodies against the spike 1 protein receptor-binding domain against severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2 RBD-S1) were analyzed in both serum and HM samples. RESULTS: Most of the participants (ie, 94%) received the BNT162b2 messenger RNA COVID-19 vaccine. The mean serum concentration of anti-SARS-CoV-2 RBD-S-IgG antibodies in vaccinated individuals was 3379.6 ± 1639.5 binding antibody units per mL. All vaccinated study participants had anti-SARS-CoV-2 RBD-S1-IgG, and 89% of them had anti-SARS-CoV-2 RBD-S-IgA in their milk. The antibody concentrations in the milk of mothers who were breastfeeding 24 months were significantly higher than in mothers with breastfeeding periods <24 months (P < .001). CONCLUSIONS: We found a clear association between COVID-19 vaccination and specific immunoglobulin concentrations in HM. This effect was more pronounced when lactation periods exceeded 23 months. The influence of the lactation period on immunoglobulins was specific and independent of other variables.

High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

BACKGROUND & AIMS: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. METHODS: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded. RESULTS: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. CONCLUSIONS: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.