Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly ( p -value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.

Viral etiology is not uncommon among those evaluated for CNS infection in Qatar. Clinical outcomes are excellent in this group of patients. Antibiotics and acyclovir are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of viral CNS infections.

The coronavirus disease 2019 (COVID-19) pandemic has been an enormous public health challenge. The pursuit for an effective therapy led to the use of the antiviral drug Remdesivir for hospitalized patients with severe COVID-19 pneumonia. We reported two cases of patients with severe COVID-19 pneumonia and worsening oxygen requirements. Both patients developed sinus bradycardia following initiation of Remdesivir therapy and reverted after stopping it. One of the patients developed QTc interval prolongation and required intensive care unit admission. The proposed mechanism for Remdesivir-induced bradycardia and cardiac toxicity could be due to the intrinsic electrophysiological properties and the effect on the AV node; yet, further large observational studies are warranted for better understanding and correlation of Remdesivir with cardiac adverse events. Till then, healthcare providers need to be alert of this potential adverse event and to monitor their COVID-19 patients closely while on Remdesivir therapy.