A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Real-world evaluation of COVID-19 lateral flow device (LFD) mass-testing in healthcare workers at a London hospital; a prospective cohort analysis.

OBJECTIVES: Real-world evaluation of the performance of the Innova lateral flow immunoassay antigen device (LFD) for regular COVID-19 testing of hospital workers. METHODS: This prospective cohort analysis took place at a London NHS Trust. 5076 secondary care healthcare staff participated in LFD testing from 18 November 2020 to21 January 2021. Staff members submitted results and symptoms via an online portal twice weekly. Individuals with positive LFD results were invited for confirmatory SARS CoV-2 PCR testing. The positive predictive value (PPV) of the LFD was measured. Secondary outcome measures included time from LFD result to PCR test and staff symptom profiles. RESULTS: 284/5076 individuals reported a valid positive LFD result, and a paired PCR result was obtained in 259/284 (91.2%). 244 were PCR positive yielding a PPV of 94.21% (244/259, 95% CI 90.73% to 96.43%). 204/259 (78.8%) staff members had the PCR within 36 hours of the LFD test. Symptom profiles were confirmed for 132/244 staff members (54.1%) with positive PCR results (true positives) and 13/15 (86.6%) with negative PCR results (false positives). 91/132 true positives (68.9%) were symptomatic at the time of LFD testing: 65/91 (71.4%) had symptoms meeting the PHE case definition of COVID-19, whilst 26/91 (28.6%) had atypical symptoms. 18/41 (43.9%) staff members who were asymptomatic at the time of positive LFD developed symptoms in the subsequent four days. 9/13 (76.9%) false positives were asymptomatic, 1/13 (7.7%) had atypical symptoms and 3/13 (23.1%) had symptoms matching the PHE case definition. CONCLUSIONS: The PPV of the Innova LFD is high when used amongst hospital staff during periods of high prevalence of COVID-19, yet we find frequent use by symptomatic staff rather than as a purely asymptomatic screening tool. LFD testing does allow earlier isolation of infected workers and facilitates detection of individuals whose symptoms do not qualify for PCR testing.