Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes were associated with distinct clinical features including age, sex, severity, and disease stages of COVID-19. SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19.

Objectives COVID-19 has a varied clinical presentation. Elderly patients with comorbidities are more vulnerable to severe disease. This study identifies specific symptoms and comorbidities predicting severe COVID-19 and intensive care unit (ICU) admission. Methods A literature search identified studies indexed in MEDLINE, EMBASE and Global Health before 5th March 2020. Two reviewers independently screened the literature and extracted data. Quality appraisal was performed using STROBE criteria. Random effects meta-analysis identified symptoms and comorbidities associated with severe COVID-19 or ICU admission. Results Seven studies (including 1813 COVID-19 patients) were included. ICU patients were older (62.4 years) than non-ICU (46 years), with a greater proportion of males. Dyspnoea was the only symptom predictive for severe disease (pOR 3.70, 95% CI 1.83-7.46) and ICU admission (pOR 6.55, 95% CI 4.28-10.0). COPD was the strongest predictive comorbidity for severe disease (pOR 6.42, 95% CI 2.44-16.9) and ICU admission (pOR 17.8, 95% CI 6.56-48.2), followed by cardiovascular disease and hypertension. Conclusions Dyspnoea was the only symptom predictive for severe COVID-19 and ICU admission. Patients with COPD, cardiovascular disease and hypertension were at higher risk of severe illness and ICU admission.

The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.

Background/introductionCOVID-19, a novel coronavirus outbreak starting in China, is now a rapidly developing public health emergency of international concern. The clinical spectrum of COVID-19 disease is varied, and identifying factors associated with severe disease has been described as an urgent research priority. It has been noted that elderly patients with pre-existing comorbidities are more vulnerable to more severe disease. However, the specific symptoms and comorbidities that most strongly predict disease severity are unclear. We performed a systematic review and meta-analysis to identify the symptoms and comorbidities predictive of COVID-19 severity. MethodThis study was prospectively registered on PROSPERO. A literature search was performed in three databases (MEDLINE, EMBASE and Global Health) for studies indexed up to 5 th March 2020. Two reviewers independently screened the literature and both also completed data extraction. Quality appraisal of studies was performed using the STROBE checklist. Random effects meta-analysis was performed for selected symptoms and comorbidities to identify those most associated with severe COVID-19 infection or ICU admission. ResultsOf the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID-19 patients) were chosen for inclusion. The ICU group were older (62.4 years) compared to the non-ICU group (46 years), with a significantly higher proportion of males (67.2% vs. 57.1%, p=0.04).Dyspnoea was the only significant symptom predictive for both severe disease (pOR 3.70, 95% CI 1.83 -7.46) and ICU admission (pOR 6.55, 95% CI 4.28-10.0). Notwithstanding the low prevalence of COPD in severe disease and ICUadmitted groups (4.5% and 9.7%, respectively), COPD was the most strongly predictive comorbidity for both severe disease (pOR 6.42, 95% CI 2. 44 -16.9) and ICU admission (pOR 17.8, 95% CI 6.56 -48.2). Cardiovascular disease and All rights reserved. No reuse allowed without permission. perpetuity. : medRxiv preprint hypertension were also strongly predictive for both severe disease and ICU admission. Those with CVD and hypertension were 4.4 (95% CI 2.64 -7.47) and 3.7 (95% CI 2.22 -5.99) times more likely to have an ICU admission respectively, compared to patients without the comorbidity. ConclusionsDyspnoea was the only symptom strongly predictive for both severe disease and ICU admission, and could be useful in guiding clinical management decisions early in the course of illness. When looking at ICU-admitted patients, who represent the more severe end of the spectrum of clinical severity, COPD patients are particularly vulnerable, and those with cardiovascular disease and hypertension are also at a high-risk of severe illness. To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID-19.