Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Mechanism of Salmonella reduction in fermented pig feed

To protect consumers from Salmonella infection acquired through the consumption of pork meat, it is necessary to eradicate Salmonella from pork. In order to achieve this, the whole pork production chain should be free from Salmonella, including the pigs at the farm. In epidemiological studies it was concluded that the use of fermented feed plays a significant role in the reduction of Salmonella prevalence in pig farms. However, the mechanism of Salmonella reduction in fermented feed is not known. A controlled feed fermentation was performed using a pure culture of Lactobacillus plantarum, pH reduction, organic acid profiles and bacterial counts were determined. In L plantarum-fermented feed, lactic acid and acetic acid were produced and the pH dropped to a value below 4.0. Antimicrobial products (bacteriocins) could not be detected. The results showed that the produced lactic and acetic acid and the pH in the feed are responsible for Salmonella reduction in fermented feed. L plantarum did not show any other antimicrobial effect on Salmonell

Mechanism of Salmonella reduction in fermented pig feed

To protect consumers from Salmonella infection acquired through the consumption of pork meat, it is necessary to eradicate Salmonella from pork. In order to achieve this, the whole pork production chain should be free from Salmonella, including the pigs at the farm. In epidemiological studies it was concluded that the use of fermented feed plays a significant role in the reduction of Salmonella prevalence in pig farms. However, the mechanism of Salmonella reduction in fermented feed is not known. A controlled feed fermentation was performed using a pure culture of Lactobacillus plantarum, pH reduction, organic acid profiles and bacterial counts were determined. In L plantarum-fermented feed, lactic acid and acetic acid were produced and the pH dropped to a value below 4.0. Antimicrobial products (bacteriocins) could not be detected. The results showed that the produced lactic and acetic acid and the pH in the feed are responsible for Salmonella reduction in fermented feed. L plantarum did not show any other antimicrobial effect on Salmonell

Monitoring of transmission of Salmonella enterica serovars in pigs using bacteriological and serological detection methods

The standard method to detect Salmonella positive pigs is bacteriological examination of the faeces, but in recent years the use of Salmonella-ELISA’s have become available to screen pigs for serological evidence of infection. This study was conducted to monitor the transmission of five different Salmonella enterica serovars (S. Typhimurium, S. Brandenburg, S. Panama, S. Livingstone, and S. Goldcoast) in fattening pigs and to test the feasibility of Salmonella-ELISA, using seeder pigs as a mode of transmission. Serovar dependence in transmission was observed. The Salmonella-ELISA proved to be useful to detect S. Typhimurium and S. Brandenburg in herds but was of limited value to demonstrate S. Livingstone, S. Goldcoast, and S. Panama

Monitoring of transmission of Salmonella enterica serovars in pigs using bacteriological and serological detection methods

The standard method to detect Salmonella positive pigs is bacteriological examination of the faeces, but in recent years the use of Salmonella-ELISA’s have become available to screen pigs for serological evidence of infection. This study was conducted to monitor the transmission of five different Salmonella enterica serovars (S. Typhimurium, S. Brandenburg, S. Panama, S. Livingstone, and S. Goldcoast) in fattening pigs and to test the feasibility of Salmonella-ELISA, using seeder pigs as a mode of transmission. Serovar dependence in transmission was observed. The Salmonella-ELISA proved to be useful to detect S. Typhimurium and S. Brandenburg in herds but was of limited value to demonstrate S. Livingstone, S. Goldcoast, and S. Panama