November 10 | Daily COVID-19 LST Report

Transmission & Prevention

· Pediatricians published best practices for breastfeeding mothers who were positive for or exposed to COVID-19 in JAMA Pediatrics. The authors express that while the literature is uncertain on risk of COVID-19 transmission through breastmilk, this route of transmission seems unlikely, and protective antibodies are likely to be the only SARS-CoV-2 related material to be transmitted. They believe their proposed practices for breastfeeding while infected with COVID-19 will promote safe breastfeeding, although they note these suggestions may change overtime.

· Is there an association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19? Investigators on the STOP-COVID (Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19) team retrospectively analyzed data of 3,924 COVID-19 patients from 68 US hospitals admitted to the ICU. They compared estimated 30-day mortality rates of patients that received tocilizumab (an IL-6 inhibitor) in the first 2 days of ICU admission verses those who did not. The researchers performed inverse probability weighting to ensure that baseline and severity of illness factors were balanced between the study groups. The results revealed an estimated 30-day mortality of 27.5% in patients treated with tocilizumab, compared to 37.1% in patients without tocilizumab, suggesting the drug's benefit in treatment of critically ill COVID-19 patients. · Investigators affiliated with Yale School of Medicine performed a systematic review of 86 studies worldwide (n=2560 patients) on dermatologic manifestations in COVID-19 patients and found associations with chilblains/pernio like lesions at 51.5%, erythematous maculopapular rashes at 13.3%, and viral exanthem at 7.7%. Average time of skin lesion onset was 7.9 days after upper respiratory infection symptoms in adults and 1.5 days in children. These findings suggest that dermatologic manifestations may be another way to identify COVID-19 and better manage the spread of disease. R&D: Diagnosis & Treatments

· At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of 32 longitudinal studies examined the accuracy, temporal sensitivity, and optimal sampling sites and strategies for SARS-CoV-2. The authors reported on a total of 1,023 COVID-19 RT-PCR confirmed participants and 1,619 test results for 11 different sampling sites at various times during SARS-CoV-2 infection. They found that the highest rate of virus detection was within 4 days of symptom onset at 89%, which fell to 54% between 10 and 14 days. The authors discuss that the accuracy of RT-PCR is limited, early testing minimizes false negative results, and lower respiratory tract or fecal testing may be preferred sampling sites when testing more than a few days post symptom onset.

· There is clinical impact of monocyte distribution width and neutrophil-to-lymphocyte ratio for distinguishing COVID-19 and influenza from other upper respiratory tract infections according to a cohort study conducted at Taipei Medical University Hospital (Taiwan), that analyzed potential biomarkers of SARS-CoV-2 infection in 174 patients (9 with nasal swab RT-PCR confirmed COVID-19, 24 with influenza confirmed via rapid-test, and 141 determined to have common URIs). The authors found that monocyte distribution width (MDW) greater than or equal to 20 (OR: 8.39, p = 0.0110) and neutrophil-to-lymphocyte ratio greater than 3.2 (OR: 4.23, p = 0.0494) could independently distinguish COVID-19 from common upper respiratory infections. Further, combining these two markers shows promise for efficient identification of both COVID-19 and influenza infection. For clinicians uncertain about diagnosing COVID-19 or those doubting a test result, this information may become a useful tool in identifying COVID-19.

· A multidisciplinary group of drug development experts from the UK, USA, Switzerland and Italy reviewed literature on effects of antiviral protein binding on in-vivo drug activity by assessing data from antiretroviral drug development and reached a consensus. They found that unbound plasma concentrations could not be compared to in-vitro activity and researchers must instead compare in-vivo and in-vitro free drug concentrations. They cited recent studies investigating remdesivir and lopinavir as possible agents against SARS-CoV-2, which do not account for protein binding. They argue correct interpretation of protein binding data is critical for identification of the most promising drug candidates.

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