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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22282730

RESUMO

BackgroundSARS-CoV-2 transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors. MethodsWe analyzed a COVID-19 prospective household transmission cohort in North Carolina (April-Oct 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between Days 7-14. ResultsIn the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between Days 7-14 was reported by 26% of household contacts, and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case. ConclusionIn-home masking during household exposure to COVID-19 was infrequent in 2020. In light of ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21258639

RESUMO

BackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21258011

RESUMO

BackgroundWhile SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection. MethodsCOVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. ResultsAmong 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001). ConclusionsThe presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. ClinicalTrials.gov IdentifierNCT04405570 Key Points (Summary)Among COVID-19 outpatients within 7 days of symptom onset, the presence of SARS-CoV-2-specific antibodies was strongly associated with clearance of infectious virus. Seropositivity appears to be more reliable marker of infectious virus clearance than subjective measure of COVID-19 symptoms.

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