The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

Key Points Question What key biological characteristics of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and placental function and pathology have implications for vertical transmission and neonatal protection? Findings In this prospective cohort study including 127 pregnancies, there was no maternal viremia, placental infection, or vertical transmission of SARS-CoV-2. Compromised transplacental transfer of anti–SARS-CoV-2 antibodies with robust transfer of influenza-specific immunity and nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 were noted. Meaning These findings suggest that, although low rates of maternal viremia and patterns of placental SARS-CoV-2 receptor distribution may underlie the rarity of vertical transmission, reduced transplacental transfer of anti–SARS-CoV-2 antibodies may leave neonates at risk for infection.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.

Coronavirus disease 2019 (COVID‐19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis‐4 (FIB‐4) score for a cohort of hospitalized patients with COVID‐19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS‐CoV‐2 by nasopharyngeal sampling were included in this analysis. FIB‐4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB‐4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB‐4 and SARS‐CoV‐2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB‐4 in participants who survived and died were 1.91 and 3.98 ( P < 0.001 by Mann‐Whitney U test), respectively. Each one‐unit increment in FIB‐4 was associated with an increased odds of death (odds ratio, 1.79; 95% confidence interval, 1.36, 2.35; P < 0.001) after adjusting for baseline characteristics including sex, body mass index, hypertension, diabetes, and history of liver diseases. During hospitalization, FIB‐4 peaked and then normalized in the survival group but failed to normalize in the death group. FIB‐4 was positively correlated with the level of SARS‐CoV‐2 viral load and monocyte‐associated cytokines, especially interleukin‐6 and interferon gamma–induced protein 10. Conclusion: FIB‐4 is associated with mortality in COVID‐19, independent of underlying conditions including liver diseases. FIB‐4 may be a simple and inexpensive approach to risk‐stratify individuals with COVID‐19.

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SARS-CoV-2 kinetics remain understudied, including the impact of remdesivir. In hospitalized individuals, peak sputum viral load occurred in week 2 of symptoms while peak viremia occurred within a week of symptom-onset, suggesting early systemic seeding of SARS-CoV-2. Remdesivir treatment was associated with faster rates of viral decay.

Background Biological sex and the estrogen receptor (ESR1) modulate residual HIV activity. Few women have been enrolled in clinical trials of latency reversal agents(LRAs); their effectiveness in women is unknown. We hypothesized that ESR1 antagonism would augment induction of HIV expression by the LRA vorinostat. Methods ACTG A5366 enrolled 31 virologically suppressed, postmenopausal women on antiretroviral therapy(ART). Participants were randomized 2:1 to receive tamoxifen(Arm A, TAMOX/VOR) or observation(Arm B, VOR) for five weeks followed by two doses of vorinostat. Primary endpoints were safety and the difference between arms in HIV RNA induction after vorinostat. Secondary analyses included histone 4 acetylation, HIV DNA, and plasma viremia by single copy assay(SCA). Results No significant adverse events were attributed to study treatments. Tamoxifen did not enhance vorinostat-induced HIV transcription (between-arm ratio 0.8 [95% CI 0.2,2.4]). Induction of spliced HIV RNA transcripts was higher among the 18 participants with increases in H4Ac (fold increase 2.78 [95% CI 1.34,5.79]) versus the 9 who did not (fold increase 1.04 [95% CI 0.25,4.29]). HIV DNA and plasma viremia by SCA did not substantially change. Conclusions Tamoxifen did not augment vorinostat-induced HIV RNA expression in post-menopausal women. The modest latency reversal activity of vorinostat, postmenopausal status and HIV RNA near the limits of quantification limited assessment of the impact of tamoxifen. This study is the first HIV cure trial done exclusively in women, establishes both the feasibility and necessity of investigating novel HIV cure strategies in women living with HIV.