SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Effect of COVID-19 restrictions and border closures on vaccine preventable diseases in Victoria, Australia, 2020-2021.

Background: In 2020, Victoria introduced multiple interventions aimed at containing the spread of coronavirus disease 2019 (COVID-19). We examine the effect of these restrictions on other vaccine preventable diseases (VPDs). Methods: We analysed the mandatory reporting data, notified to the Victorian Department of Health, for VPDs from January 2015 to December 2021. Results: Reductions in notifications were seen for most notifiable VPDs. A precipitous decline in influenza and measles notifications was recorded in April 2020, which was sustained for both diseases throughout 2020-2021. Notifications for chickenpox, invasive meningococcal disease, invasive pneumococcal disease, and pertussis were reduced by greater than 50% from the 2015-2019 average. No notified cases of diphtheria, poliomyelitis, or rubella were reported in 2020-2021. Conclusion: Restrictions placed to mitigate the effects of the COVID-19 pandemic were associated with significant reductions in other VPDs, which were sustained into 2021. Nevertheless, it is important that high levels of population vaccine coverage continue, to prevent a rebound increase in VPDs as restrictions are eased, and to maximise protection against VPDs for all Australians.

COVID-Care – a safe and successful digital self-assessment tool for outpatients with proven and suspected coronavirus-2019

Introduction The coronavirus-2019 (COVID-19) pandemic and restrictions placed on movement to prevent its transmission have led to a surge in demand for remote medical care. We investigated whether COVID-Care, a patient-reported, telehealth, symptom monitoring system, was successful at delivering safe monitoring and care for these patients leading to decreased hospital presentations. Methods We performed a single centre, prospective, interventional cohort study with symptomatic outpatients who presented for COVID-19 screening at Austin Health, Australia. Participants were invited to take part in the COVID-Care programme, entering common COVID-19 symptoms on a purpose-built, online survey monitored by infectious diseases physicians, and matched with clinical data including date of symptom onset, hospital admission, and screening clinic presentations. Results 42,158 COVID-19 swabs were performed in 31,626 patients from March to October 2020, with 414 positive cases. 20,768 people used the COVID-Care survey at least once. COVID-Care users were significantly younger than non-users. Of the 414 positive cases, 254 (61.3%) used COVID-Care, with 160 (38.6%) non-users. Excluding presentations on the same day or prior to the COVID-19 swab, of the positive cases there were 56 hospital presentations. 4.3% (11) of COVID-Care users and 28.1% (45) non-users were admitted to hospital or the emergency department (p < 0.001), with 3.9% (10) versus 22.5% (36) requiring inpatient admission (p < 0.001). There were no deaths in COVID-Care users versus 2 deaths in non-users. Conclusion COVID-Care, a digitally integrated, outpatient, symptom tracking and telemedical service for patients with COVID-19, was safe and successful at reducing hospital and emergency department admissions, suggesting a strong role for telemedicine for future healthcare delivery in this logistically challenging setting.

Practical ethical challenges and moral distress among staff in a hospital COVID-19 screening service.

The COVID-19 pandemic has led to unprecedented disruptions to established models of healthcare and healthcare delivery, creating a host of new ethical challenges for healthcare institutions, their leadership and their staff. Hospitals and other large organisations have an obligation to understand and recognise the downstream effects that highly unusual situations and professionally demanding policy may have on workers tasked with its implementation, in order to institute risk-mitigation strategies and provide additional support where required. In our experience, targeted ethics-based forums that provide a non-confrontational platform to discuss and explore the ethical dilemmas that may have arisen have been well received, and can also serve as useful and immediate feedback mechanisms to managers and leadership. Using two case illustrations, this article examines some of the ethical challenges and dilemmas faced by these staff, based on discussions of shared experience during a clinical ethics forum for the Screening Clinic staff at Austin Health, Melbourne, Victoria.

Defective Severe Acute Respiratory Syndrome Coronavirus 2 Immune Responses in an Immunocompromised Individual With Prolonged Viral Replication.

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR+/CD38+ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2-specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

The Role of Immunological and Clinical Biomarkers to Predict Clinical COVID-19 Severity and Response to Therapy-A Prospective Longitudinal Study.

Background: The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined. Methods: A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited - blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC). Results: IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06, 35.77) in patients with NIC; and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was amplified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity. Conclusions: Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.

Multi-site assessment of rapid, point-of-care antigen testing for the diagnosis of SARS-CoV-2 infection in a low-prevalence setting: A validation and implementation study.

BACKGROUND: In Australia, COVID-19 diagnosis relies on RT-PCR testing which is relatively costly and time-consuming. To date, few studies have assessed the performance and implementation of rapid antigen-based SARS-CoV-2 testing in a setting with a low prevalence of COVID-19 infections, such as Australia. METHODS: This study recruited participants presenting for COVID-19 testing at three Melbourne metropolitan hospitals during a period of low COVID-19 prevalence. The Abbott PanBioTM COVID-19 Ag point-of-care test was performed alongside RT-PCR. In addition, participants with COVID-19 notified to the Victorian Government were invited to provide additional swabs to aid validation. Implementation challenges were also documented. FINDINGS: The specificity of the Abbott PanBioTM COVID-19 Ag test was 99.96% (95% CI 99.73 - 100%). Sensitivity amongst participants with RT-PCR-confirmed infection was dependent upon the duration of symptoms reported, ranging from 77.3% (duration 1 to 33 days) to 100% in those within seven days of symptom onset. A range of implementation challenges were identified which may inform future COVID-19 testing strategies in a low prevalence setting. INTERPRETATION: Given the high specificity, antigen-based tests may be most useful in rapidly triaging public health and hospital resources while expediting confirmatory RT-PCR testing. Considering the limitations in test sensitivity and the potential for rapid transmission in susceptible populations, particularly in hospital settings, careful consideration is required for implementation of antigen testing in a low prevalence setting. FUNDING: This work was funded by the Victorian Department of Health and Human Services. The funder was not involved in data analysis or manuscript preparation.