Background Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. Methods In this ongoing, double-blind, phase 1–3 tr...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2035002?articleTools=true

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of coronavirus disease 2019 (COVID-19), is readily transmitted person to person. Optimal control of COVID-19 depends on directing resources and health messaging to mitigation efforts that are most likely to prevent transmission, but the relative importance of such measures has been disputed. Objective To assess the proportion of SARS-CoV-2 transmissions in the community that likely occur from persons without symptoms. Design, Setting, and Participants This decision analytical model assessed the relative amount of transmission from presymptomatic, never symptomatic, and symptomatic individuals across a range of scenarios in which the proportion of transmission from people who never develop symptoms (ie, remain asymptomatic) and the infectious period were varied according to published best estimates. For all estimates, data from a meta-analysis was used to set the incubation period at a median of 5 days. The infectious period duration was maintained at 10 days, and peak infectiousness was varied between 3 and 7 days (−2 and +2 days relative to the median incubation period). The overall proportion of SARS-CoV-2 was varied between 0% and 70% to assess a wide range of possible proportions. Main Outcomes and Measures Level of transmission of SARS-CoV-2 from presymptomatic, never symptomatic, and symptomatic individuals. Results The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms. Conclusions and Relevance In this decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods, transmission from asymptomatic individuals was estimated to account for more than half of all transmissions. In addition to identification and isolation of persons with symptomatic COVID-19, effective control of spread will require reducing the risk of transmission from people with infection who do not have symptoms. These findings suggest that measures such as wearing masks, hand hygiene, social distancing, and strategic testing of people who are not ill will be foundational to slowing the spread of COVID-19 until safe and effective vaccines are available and widely used.

/pdf/sars-cov-2-transmission-from-people-without-covid-19-2hvrttxho7.pdf

SARS-CoV-2 Transmission From People Without COVID-19 Symptoms.

Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.

Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors.

https://escholarship.org/content/qt1k5378ws/qt1k5378ws.pdf?t=qnu6z3

Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy.

Importance There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. Design, Setting, and Participants A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea. Main Outcomes and Measures Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients’ symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription–polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients. Results Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (β = −0.065 [SE, 0.023];P = .005). Conclusions and Relevance In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.

/pdf/clinical-course-and-molecular-viral-shedding-among-3ialpoao6x.pdf

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

/pdf/multidisciplinary-intestinal-rehabilitation-in-children-2rxiiatg5q.pdf

Cheolgu Lee

Papers

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

Multidisciplinary Intestinal Rehabilitation in Children: Results from a Korean Intestinal Rehabilitation Team