Publications

The replication of SARS-CoV-2 and other coronaviruses depends on transcription of negative-sense RNA intermediates that serve as the templates for the synthesis of positive-sense genomic RNA (gRNA) and multiple different subgenomic mRNAs (sgRNAs) encompassing fragments arising from discontinuous transcription. Recent studies have aimed to characterize the expression of subgenomic SARS-CoV-2 transcripts in order to investigate their clinical significance. Here, we describe a novel panel of reverse transcription droplet digital PCR (RT-ddPCR) assays designed to specifically quantify multiple different subgenomic SARS-CoV-2 transcripts and distinguish them from transcripts that do not arise from discontinuous transcription at each locus. These assays can be applied to samples from SARS-CoV-2 infected patients to better understand the regulation of SARS-CoV-2 transcription and how different sgRNAs may contribute to viral pathogenesis and clinical disease severity.

BACKGROUND

HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, while data for HCV are sparse.

METHODS

We performed repeat echocardiography over a median interval of 12 years in participants from the Women's Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic).

RESULTS

Of the 311 women included (age 39 ± 9), 70% were HIV and 20% HCV positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared to participants with neither infection, the group with HIV-HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors (RR = 2.96 [95% CI = 1.05-8.31]), but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant (RR = 2.54 [0.83-7.73] and RR = 1.66 [0.65-4.25], respectively). Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates (RR = 1.96 [1.02-3.77]), but this was not the case for HIV-positive vs. HIV-negative women (RR = 1.43 [0.76-2.69]). There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though non-significant, risk estimate for HCV.

CONCLUSIONS

Among middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.