Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity (preprint)

Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation (preprint)

Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, {gamma}{delta} T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of {beta} CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1{beta}, IFN-{gamma}, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.

The Use of Procalcitonin as an Antimicrobial Stewardship Tool and a Predictor of Disease Severity in COVID-19 (preprint)

In our study, procalcitonin was associated with both antibiotic use and duration in patients with COVID-19, as well as established biochemical markers of COVID-19 disease severity and oxygen requirement, suggesting a potential role for procalcitonin in COVID-19 antimicrobial stewardship.

Staff to staff transmission as a driver of healthcare worker infections with COVID-19 (preprint)

Objectives: To investigate the COVID-19 infections among staff at our institution and determine the interventions required to prevent subsequent staff infections. Design: Retrospective cohort study Participants and setting: Staff working at a single tertiary referral hospital who returned a positive test result for SARS-CoV-2 between 25 January 2020 and 25 November 2020. Main outcome measures: Source of COVID-19 infection. Results: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at Austin Health. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-staff transmission, including 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. Investigation of the outbreak identified the staff tearoom as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. Conclusions: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.

COVID-MATCH65 - A prospectively derived clinical decision rule for severe acute respiratory syndrome coronavirus 2 (preprint)

Due to the ongoing COVID-19 pandemic and increased pressure on testing resources, understanding the clinical and epidemiological features closely associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is vital at point of care to enable risk stratification. We demonstrate that an internally derived and validated clinical decision rule, COVID-MATCH65, has a high sensitivity (92.6%) and NPV (99.5%) for SARS-CoV-2 and could be used to aid COVID-19 risk-assessment and resource allocation for SARS-CoV-2 diagnostics.