SARS-CoV-2 viremia in patients hospitalised for COVID-19

Abstract: More than 6.6 million people have died from Covid-19 since the SARS-CoV-2 outbreak started in Wuhan, China, late 2019. The spread of the novel virus necessitated knowledge on how to manage this new disease. This project focused on SARS-CoV-2 viremia with the overall aim of improving the understanding and clinical management of patients hospitalised with Covid-19. Paper I analysed the association of SARS-CoV-2 viremia at admission to critical disease and/or 28- day mortality. A total of 167 patients hospitalised for Covid-19 were included, of whom 37% (61/167) were viremic. There was a 7.2 times increased risk of critical disease, and an 8.6 times increased risk of 28-day mortality in patients with viremia compared to non-viremic patients. Paper II explored the duration of viremia and its correlation to mortality and inflammatory parameters in a cohort of 121 viremic patients. The median time from admission to clearance of SARS-CoV-2 viremia was 7 days. The odds of in-hospital mortality increased with 40% for each additional day of viremia. Clearance of viremia coincided with decreasing levels of C-reactive protein and normalisation of body temperature. Paper III investigated the association of nasopharyngeal viral load at admission to viremia and adverse outcomes in a cohort of 688 patients. There was a dose-dependent association between nasopharyngeal viral load and viremia. There was a 4.4 times and 2.0 times increased odds of being viremic for patients with low and intermediate nasopharyngeal Cycle Threshold values (indicating high and intermediate viral loads), compared to patients with high Cycle Threshold values. Moreover, the risk for 60-day mortality was increased in patients with low nasopharyngeal Cycle Threshold values. Paper IV studied the effects of antiviral treatment with remdesivir on SARS-CoV-2 viremia and outcome. In this cohort of 318 severely ill, viremic patients, 33% (105/318) received remdesivir treatment. No significant differences were seen on the duration of viremia or adverse outcomes between the groups. However, a trend towards a higher rate of serum viral clearance was seen when restricting the cohort to a subgroup with ≤ 7 days from symptom onset to admission. This thesis thus showed that nasopharyngeal viral load was associated with viremia, possibly indicating poor viral control. Both high nasopharyngeal viral load and viremia at admission were markers of increased risk for critical disease and death. Each additional day of viremia correlated to increased risk of mortality whilst clearance of viremia was associated with decreasing inflammatory parameters. Viremic patients receiving remdesivir had a trend towards shorter duration of viremia if given early after symptom onset. However, remdesivir treatment was not associated with a reduction of mortality in this project. As viremia was a robust predictor of severe outcome, probably associated to poor viral control and high grade inflammation, it could possibly be used to identify patients who should be prioritised for treatment with highly active antivirals and anti-inflammatory drugs.

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