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SARS-CoV-2 RNAemia predicts clinical deterioration and extrapulmonary complications from COVID-19
BLUF

A prospective cohort study conducted by researchers from Stanford University School of Medicine collected plasma and analyzed quantitative (qPCR) and digital PCR (dPCR) to quantify SARS-CoV-2 RNA from 191 patients who presented to the ED with COVID-19 infection. Twenty-three percent (44/191) of SARS-CoV-2 positive patients had viral RNA detected in plasma by dPCR compared to 1.4% (2/147) by qPCR, indicating than dPCR is more sensitive than qPCR for detection of SARS-CoV-2 RNAemia. Compared with non-RNAemic patients, those with RNAemia were more likely to develop severe disease (odds ratio 6.72 [95% CI, 2.45 – 19.79]) (Figure 2), and require hospital admission (90.9% vs 70.1%, difference = 20.8% [95% CI, 8.1%-33.6%]), and tended toward higher rates of all EPC categories (p < 0.05) (Figure 4). These findings demonstrate how RNAemia on presentation could serve as an indicator for early therapies to be administered for the patients at highest risk for severe COVID-19 infection and deterioration.

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Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients
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In a research letter, surgery and pathology specialists associated with Johns Hopkins University School of Medicine discuss their study on antibody responses by 2-dose SARS-CoV-2 mRNA vaccination in 658 transplant recipients. At a median of 21 days after dose 1, antibody was detected in 98 participants (15%) with median antibody levels of > 250 U/mL (Roche Elecsys anti–SARS-CoV-2 S enzyme immunoassay) and 9.23 arbitrary units (EUROIMMUN enzyme immunoassay) (Figure). Antibodies were detected in 357 participants (54%) after a median of 29 days after dose 2, with a median antibody level of 142.1 U/mL (Roche) and 6.48 arbitrary units (EUROIMMUN). These results suggest that although a higher antibody response was noted after dose 2, transplant recipients still have a substantial risk of acquiring COVID-19.

Summary

- Use of antimetabolite immunosuppression was associated with poor antibody responses.

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Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial
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Brazilian researchers conducted a randomized, double-blinded, placebo-controlled, phase 2b trial between April 18-June 16, 2020 to assess the efficacy of methylprednisolone (MP) in treating hospitalized COVID-19 patients (Figure 1). They performed modified intention to treat (mITT) analysis of 393 participants (194 in MP and 199 in placebo group) and found no significant difference in the primary outcome (28 day mortality) and secondary outcomes (summary) between the two groups. Post hoc analysis revealed lower 28 day mortality in ages over 60 in the MP group (Tables 1,2). Authors conclude that methylprednisolone did not lower mortality in hospitalized COVID-19 patients.

Summary

Metacovis is a randomized, double-blinded, placebo-controlled, phase 2b trial conducted from April 18-June 16, 2020 to assess the efficacy of methylprednisolone (MP) in treating hospitalized COVID-19 patients more than 18 years of age. They randomized 416 participants and performed mITT analysis in 393 participants with 194 in MP (twice daily for 5 days) and 199 in the placebo arm.

Primary outcome: 28 day mortality
Secondary outcomes: early mortality, need for endotracheal intubation, and PaO2/FiO2 less than 100 on day 7

They found:
- No significant differences in the 28 day mortality by group. 76/199 in placebo and 72/194 in MP (p=0.629).
- Subgroup analysis revealed decreased mortality in MP arm for patients over 60 years old.
- Radiologic evidence of Bronchiolitis Obliterans with Organizing Pneumonia and pulmonary fibrosis did not differ significantly between MP and placebo
- No increased occurrence of sepsis in the MP group
- Requirement of more insulin in MP arm

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Asymptomatic Transmission and the Infection Fatality Risk for COVID-19: Implications for School Reopening
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An epidemiologist and pediatrician from Yale review data regarding asymptomatic SARS-CoV-2 infection, COVID-19 fatality risk, and how these factors should influence school reopening. They found now-ubiquitous prevention measures (physical distancing, wearing masks, personal hygiene) appear to minimize asymptomatic infections. Using case fatality risk rather than infection fatality risk, authors argue mortality from influenza is consistently lower in school-aged populations and that reopening schools can occur safely with the implementation of strict adherence to infection prevention protocols to minimize asymptomatic transmission.

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The Relationship Between Smoking and COVID-19 Progression
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Epidemiologists affiliated with the College of Public Health at Zhengzhou University and Hainan Medical University in China present a letter to the editor responding to a published systematic review and meta analysis that concluded smoking was a risk factor for COVID-19 progression, alleging that some included studies failed to properly delineate never-smokers from current non-smokers. They also discuss how the inclusion of retrospective studies and case series reports could adversely increase the heterogeneity of the study. They conclude that caution should be taken in interpreting the results of this particular study.

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