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Objectives: To investigate temporal changes in the association between SARS‐CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods: Serial oropharyngeal and blood samples were obtained from hospitalized COVID‐19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results: Elevated admission levels of IL (interleukin)‐6, IL‐33, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), interferon‐γ‐induced protein 10 (IP‐10), IL‐1β, and IL‐1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP‐10 and MCP‐1 at days 3–5, accompanied by IL‐8 and IL‐6 at days 7–10. Finally, there was a seemingly additive effect of IP‐10, MCP‐1, and IL‐6 in predicting severe outcomes when combined with high VL at baseline. Conclusions: An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID‐19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID‐19, we examined circulating levels of mediators involved in various aspects of these processes in COVID‐19 patients. Methods: Serial blood samples were obtained from two cohorts of hospitalised COVID‐19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3‐month follow‐up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60‐day total mortality and pulmonary pathology after 3‐months. We also evaluated the direct effect of inactivated SARS‐CoV‐2 on the release of the different ECM mediators in relevant cell lines. Results: Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium‐binding protein A12 and YKL‐40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3‐months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS‐CoV‐2 suggesting a direct link between these mediators and the causal agent of COVID‐19. Conclusion: Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL‐40 in the pathogenesis of severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background: T‐cell activation is associated with an adverse outcome in COVID‐19, but whether T‐cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. Objectives: To investigate whether T‐cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID‐19. Methods: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID‐19 (n = 414) were analyzed for soluble (s) markers of T‐cell activation (sCD25) and exhaustion (sTim‐3) during hospitalization and follow‐up. Results: Both markers were strongly associated with acute respiratory failure, but only sTim‐3 was independently associated with 60‐day mortality. Levels of sTim‐3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Conclusion: Our findings suggest prolonged T‐cell exhaustion is an important immunological sequela, potentially related to long‐term outcomes after severe COVID‐19. [ABSTRACT FROM AUTHOR]