Corrigendum: Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequelae of SARS-CoV-2 infection.

[This corrects the article DOI: 10.3389/fimmu.2022.1076724.].

Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals.

Background: Monocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae of SARS-CoV-2 infection (PASC) are not fully elucidated. Methods: A cross-sectional study was conducted comparing plasma cytokine and monocyte levels among three groups: participants with pulmonary PASC (PPASC) with a reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; fully recovered from SARS-CoV-2 with no residual symptoms (recovered group, RG); and negative for SARS-CoV-2 (negative group, NG). The expressions of cytokines were measured in plasma of study cohort by Luminex assay. The percentages and numbers of monocyte subsets (classical, intermediate, and non-classical monocytes) and monocyte activation (defined by CD169 expression) were analyzed using flow cytometry analysis of peripheral blood mononuclear cells. Results: Plasma IL-1Ra levels were elevated but FGF levels were reduced in PG compared to NG. Circulating monocytes and three subsets were significantly higher in PG and RG compared to NG. PG and RG exhibited higher levels of CD169+ monocyte counts and higher CD169 expression was detected in intermediate and non-classical monocytes from RG and PG than that found in NG. Further correlation analysis with CD169+ monocyte subsets revealed that CD169+ intermediate monocytes negatively correlated with DLCOc%, and CD169+ non-classical monocytes positively correlated with IL-1α, IL-1ß, MIP-1α, Eotaxin, and IFN-γ. Conclusion: This study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Further, the results suggest that monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents. This observation will aid in understanding the immunopathologic feature of pulmonary PASC development, resolution, and subsequent therapeutic interventions.

An evolving engagement programme for patients with photodermatoses

We previously reported on our experience of an in-person Scottish Photobiology Service (SPS) patient engagement event in 2019 and of its utility in defining what matters to patients with photosensitivity. We identified key issues with delays in referral from primary care, lack of availability of peer support and a need for disease-specific information to raise awareness of photosensitivity for family and employers. Through a follow- up workshop, we identified a workstream of activities planning to address these issues, which were modified by the subsequent COVID-19 pandemic. However, we successfully moved our programme to a virtual platform, and we report on our progress. Twice-yearly virtual TEAMS patient engagement half-day events, attended by patients and staff, provided patients with a forum to discuss with each other issues that they have identified as being important to them. These ranged from the isolation, anxiety and embarrassment associated with photosensitivity, dealing with friends who do not understand their condition, through to coping mechanisms and practicalities, such as sourcing sun protective clothing, dealing with sports activities and photoprotective measures in schools. The virtual events have received extremely positive feedback both in terms of content and utility for patients, as well as the convenience of the virtual format. To supplement these activities, we have also distributed twice-yearly SPS newsletters since 2020, initiated at the start of the COVID-19 pandemic, to ensure our patients knew we were there for them, despite the challenges of the pandemic and, again, this was most positively received. Regarding delays in referral from primary care, patient feedback indicated that this was mainly due to not being taken seriously, possibly due to a lack of understanding of photosensitivity in community care. We are addressing this by developing a 'photosensitivity red flag' poster for distribution throughout primary care in Scotland to raise awareness of the symptoms to look out for in photosensitivity conditions. Finally, we have also embarked on creating a series of diseasespecific podcasts. These involve an informal discussion between a patient with photosensitivity and a consultant photodermatologist, with a mediator present, to raise awareness of the true impact of a range of photodermatoses on many aspects of life. We demonstrate this ongoing programme of diverse patient engagement and educational activities in photodermatology, to highlight the model of a multifaceted hybrid approach to provide additional support for patients with photodermatoses. Acknowledgments: we wish to acknowledge all our SPS patients, their families and staff for their invaluable contributions.

Tissue- and cell-expression of druggable host proteins provide insights into repurposing drugs for COVID-19.

Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID-19). The tissue-specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID-19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half-maximal effective concentration or half-maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non-COVID-19 patients. Considerable tissue-specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis-associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell-dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell- and tissue-specific proteomics data could help interpret the in vitro antiviral activities of host-directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID-19.

Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection.

Background: Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored. Methods: Using participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry. Results: The number of LDGs was elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10+ and CD16hi subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from COVID-19 convalescents (PPASC and NRS) displayed increased markers of NET forming ability and aggregation with platelets compared to LDGs from NP, but no differences were observed between PPASC and NRS. Conclusions: Our data from a small cohort study demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in COVID-19 convalescent individuals may be associated with PPASC prognosis and development.

Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection (preprint)

Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored. Using participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry. The number of LDGs was significantly elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10+ and CD16HI subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from PPASC displayed higher NET forming ability and aggregation with platelets compared to LDGs from NP and NRS. Our data demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in individuals with PPASC may be associated with the development of long-term pulmonary sequelae.

Analysis of Benefits of an Expansion to UDOT’s Incident Management Program

In 2018 the Utah Department of Transportation (UDOT) funded a study in which data were collected to evaluate performance measures for UDOT’s Incident Management Team (IMT) program. Afterwards, UDOT received funding to expand the size of the program. Additionally, TransSuite, a data source used by the UDOT Traffic Operations Center to log incident-related data, was reconfigured to provide a higher quantity of performance measure data. This study made use of the new data source to collect performance measure data of the expanded program and measure the impacts of the IMT program expansion. Using a reanalyzed 2018 dataset and a new 2020 dataset, a comparison of performance measures was made. Performance measures were calculated for IMT responders at 320 incidents in 2018 and 289 incidents in 2020. Additionally, data regarding the affected volume, the excess travel time, and the excess user cost associated with incident congestion were gathered. In 2018 and 2020, 188 and 144 incidents were respectively analyzed for these user impacts. Statistical analyses were conducted to compare IMT performance between the two years and to determine relationships between performance measures and user impacts. The effects of the COVID-19 pandemic affected traffic volumes during this study, and statistical analyses were adjusted to account for volume differences between the two years. Results indicated that the expansion of the IMT program has allowed UDOT to respond faster to incidents, and respond to a larger quantity of incidents, even with extended coverage. Performance of the expanded IMT program has had significant effects in reducing incident-related congestion and its costs.

Cardiac MRI and Myocardial Injury in COVID-19: Diagnosis, Risk Stratification and Prognosis.

Myocardial injury is a common complication of the COVID-19 illness and is associated with a worsened prognosis. Systemic hyperinflammation seen in the advanced stage of COVID-19 likely contributes to myocardial injury. Cardiac magnetic resonance imaging (CMR) is the preferred imaging modality for non-invasive evaluation in acute myocarditis, enabling risk stratification and prognostication. Modified scanning protocols in the pandemic setting reduce risk of exposure while providing critical data regarding cardiac tissue inflammation and fibrosis, chamber remodeling, and contractile function. The growing use of CMR in clinical practice to assess myocardial injury will improve understanding of the acute and chronic sequelae of myocardial inflammation from various pathological etiologies.

A novel cohorting and isolation strategy for suspected COVID-19 cases during a pandemic.

BACKGROUND: The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. METHODS: We implemented a triage tool aimed at minimizing hospital-acquired COVID-19 particularly in patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. RESULTS: Ninety-three patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high-risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. Twenty-eight (30%) suspected COVID-19 patients were evaluated to be low risk (groups C and D) and eligible for cohorting. No symptomatic hospital-acquired infections were detected in the cohorted patients. DISCUSSION: Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital-acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.