A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections.

Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections. Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters. Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy. Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.

Longitudinal home self-collection of capillary blood using homeRNA correlates interferon and innate viral defense pathways with SARS-CoV-2 viral clearance (preprint)

Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the immune response in dynamic infections (e.g., respiratory viruses). Here we present an at-home self-collection methodology, homeRNA, to study the host transcriptional response during acute SARS-CoV-2 infections. This method uniquely enables high frequency measurement of the host immune kinetics in non-hospitalized adults during the acute and most dynamic stage of their infection. COVID-19+ and healthy participants self-collected blood every other day for two weeks with daily nasal swabs and symptom surveys to track viral load kinetics and symptom burden, respectively. While healthy uninfected participants showed remarkably stable immune kinetics with no significant dynamic genes, COVID-19+ participants, on the contrary, depicted a robust response with over 418 dynamic genes associated with interferon and innate viral defense pathways. When stratified by vaccination status, we detected distinct response signatures between unvaccinated and breakthrough (vaccinated) infection subgroups; unvaccinated individuals portrayed a response repertoire characterized by higher innate antiviral responses, interferon signaling, and cytotoxic lymphocyte responses while breakthrough infections portrayed lower levels of interferon signaling and enhanced early cell-mediated response. Leveraging cross-platform longitudinal sampling (nasal swabs and blood), we observed that IFI27, a key viral response gene, tracked closely with SARS-CoV-2 viral clearance in individual participants. Taken together, these results demonstrate that at-home sampling can capture key host antiviral responses and facilitate frequent longitudinal sampling to detect transient host immune kinetics during dynamic immune states.

The impact of COVID-19 on acute ischemic stroke admissions: Analysis from a community-based tertiary care center.

BACKGROUND/OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on hospital admissions and outcomes in patients admitted with acute ischemic stroke. METHODS: Single-center retrospective analysis of patients admitted to the hospital with acute ischemic stroke, between December 1st, 2019 and June 30th, 2020. Outcomes were classified as none-to-minimal disability, moderate-to-severe disability, and death based on discharge disposition, and compared between two time periods: pre-COVID-19 era (December 1st, 2019 to March 11th, 2020) and COVID-19 era (March 12th to June 30th, 2020). We also performed a comparative trend analysis for the equivalent period between 2019 and 2020. RESULTS: Five hundred and seventy-five patients with a mean age (years±SD) of 68±16 were admitted from December 1st, 2019 to June 30th, 2020, with a clinical diagnosis of acute ischemic stroke. Of these, 255 (44.3%) patients were admitted during the COVID-19 era. We observed a 22.1% and 39.5% decline in admission for acute ischemic stroke in April and May 2020, respectively. A significantly higher percentage of patients with acute ischemic stroke received intravenous thrombolysis during the COVID-19 era (p = 0.020). In patients with confirmed COVID-19, we found a higher percentage of older men with preexisting comorbidities such as hyperlipidemia, coronary artery disease, and diabetes mellitus but a lower rate of atrial fibrillation. In addition, we found a treatment delay in both intravenous thrombolysis (median 94.5 min versus 38 min) and mechanical thrombectomy (median 244 min versus 86 min) in patients with confirmed COVID-19 infection. There were no differences in patients' disposition including home, short-term, and long-term facility (p = 0.60). CONCLUSIONS: We observed a reduction of hospital admissions in acute ischemic strokes and some delay in reperfusion therapy during the COVID-19 pandemic. Prospective studies and a larger dataset analysis are warranted.

Computed tomography in coronavirus disease 2019: diagnosis and clinical significance

Objective To investigate the computed tomography (CT) features of the coronavirus disease 2019 (COVID-19) and the clinical significance, so as to improve our understanding of CT imaging of this disease. Methods The chest CT features of seven COVID-19 patients, who were diagnosed by virus nucleic acid test from Jan. 25 to Feb. 15, 2020 in Changhai Hospital of Naval Medical University (Second Military Medical University), were analyzed retrospectively. There were six males and one female, aged (51.1±18.8) years (range 29-75 years). All the seven patients received chest CT plain scan examimation. The CT images were interpreted by two experienced senior radiologists, and the distribution, location and density of lesions, number of involved lobes, air bronchogram, mediastinal lymphadenopathy and pleural effusion were analyzed. Results The average time from onset of symptoms to CT examination was 3.6 d (range 1-9 d) in the seven COVID-19 patients. The lesions were distributed in single lung in one case and bilateral lungs in six cases. The lesions involved middle and lateral fields of lungs in five cases and the whole field of lungs in two cases. The lesions showed ground-glass opacity in four cases and mixed shadow in three cases. The lesions involved two or less lobes in four cases and five lobes in three cases. One case had air bronchogram. No mediastinal lymphadenopathy or pleural effusion were found. Conclusion COVID-19 patients have characteristic CT findings, which has important clinical significance for the diagnosis and treatment of COVID-19. However, the diagnosis should be confirmed based on the patient's epidemic history, clinical symptoms and laboratory indicators.

COVID-19 in persons with haematological cancers.

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic with >850,000 cases worldwide and increasing. Several studies report outcomes of COVID-19 in predominately well persons. There are also some data on COVID-19 in persons with predominately solid cancer but controversy whether these persons have the same outcomes. We conducted a cohort study at two centres in Wuhan, China, of 128 hospitalised subjects with haematological cancers, 13 (10%) of whom developed COVID-19. We also studied 226 health care providers, 16 of whom developed COVID-19 and 11 of whom were hospitalised. Co-variates were compared with the 115 subjects with haematological cancers without COVID-19 and with 11 hospitalised health care providers with COVID-19. There were no significant differences in baseline co-variates between subjects with haematological cancers developing or not developing COVID-19. Case rates for COVID-19 in hospitalised subjects with haematological cancers was 10% (95% Confidence Interval [CI], 6, 17%) compared with 7% (4, 12%; P = 0.322) in health care providers. However, the 13 subjects with haematological cancers had more severe COVID-19 and more deaths compared with hospitalised health care providers with COVID-19. Case fatality rates were 62% (32, 85%) and 0 (0, 32%; P = 0.002). Hospitalised persons with haematological cancers have a similar case rate of COVID-19 compared with normal health care providers but have more severe disease and a higher case fatality rate. Because we were unable to identify specific risk factors for COVID-19 in hospitalised persons with haematological cancers, we suggest increased surveillance and possible protective isolation.