SARS-CoV-2 viral load dynamics in immunocompromised critically ill patients on remdesivir treatment

Abstract

The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long- COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 10⁷ geq/ml (±33.25 x 10⁷ geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 10⁶ geq/ml (±6.93 x 10⁶ geq/ml) on day 3 and to 1.4 x 10⁵ geq/ml (±2.35 x 10⁵ geq/ml) on day 5 of remdesivir treatment. Mean virus load dropped below <1% between day 1 and 5 of remdesivir treatment. Parent prodrug remdesivir and also GS441524 metabolite levels of antiviral activity in our patients were far in excess of EC 50. Our data present that remdesivir treatment potentially reduces the SARS-CoV-2 viral load in immunosuppressed critically ill patients. However, the implication of viral load reduction on morbidity and mortality needs further investigation.

Keywords: COVID-19; Remdesivir; SARS-CoV-2; immunosuppression; viral load.

Figure 1.

Viral dynamics during remdesivir treatment and corresponding remdesivir and metabolite plasma levels.