Top 10: July 3

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By Christian Hoffmann &
Bernd S. Kamps

3 July

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Epidemiology

Cheng SY, Wang J, Shen AC, et al. How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan. Ann Int Med 2020, Jul 2. Full-text: https://doi.org/10.7326/M20-2927

Reopening colleges and universities poses a special challenge worldwide. Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines, including a combination of strategies  such as – our future? – active campus-based screening and access control; school-based screening and quarantine protocols; student and faculty quarantine when warranted; mobilization of administrative and health center staff; regulation of dormitories and cafeterias; and reinforcement of personal hygiene, environmental sanitation, and indoor air ventilation practices. Somewhat depressing, but necessary?.

 

Callaghan AW, Chard AN, Arnold P, et al. Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities – Wyoming, 2020. MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):825-829. PubMed: https://pubmed.gov/32614815. Full-text: https://doi.org/10.15585/mmwr.mm6926a4

Following admission of two patients with SARS-CoV-2 infection on April 13, 2020, in the absence of specific guidance on prevention and management of COVID-19 in psychiatric facilities, the state hospital implemented expanded admission screening and infection prevention and control procedures. The results of the point prevalence survey, indicating no further transmission among patients and HCW almost 3 weeks after admission of the two SARS-CoV-2-positive patients, suggested that the expanded procedures might have been effective.

 

Virology

Korber B,Fischer WM, Gnanakaran S, et al. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell July 02, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.06.043

Based on 28,576 sequences until May 29, 2020, the authors show that a SARS-CoV-2 variant carrying the Spike protein amino acid change D614G (caused by an A-to-G nucleotide mutation at position 23,403 in the Wuhan reference strain) has become the most prevalent form in the global pandemic within a month. G614 has replaced D614 as the dominant pandemic form and the consistent increase of G614 at regional levels may indicate a fitness advantage. Moreover, G614 is associated with lower RT-PCR CT in the upper respiratory tract, suggestive of higher viral loads in patients. The G614 variant also grows to higher titers as pseudotyped virions. However, there was no association between G614 and disease severity.

 

Grubaugh ND, Hanage WP, Rasmussen AL. Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear. Cell July 02, 2020. Full-text:  https://doi.org/10.1016/j.cell.2020.06.040

Comment on the above work. Main message = title. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, vaccine and therapeutic development are largely unknown. As these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic.

 

Transmission

Guo L, Zhao S, Li W, et al. Absence of SARS-CoV-2 in Semen of a COVID-19 Patient Cohort. Andrology. 2020 Jun 29. PubMed: https://pubmed.gov/32598557. Full-text: https://doi.org/10.1111/andr.12848

No virus in the semen: all of 23 brave patients with SARS-CoV-2 infections (12 of them still positive in sputum and fecal specimens) tested negative for SARS‐CoV‐2 RNA in semen specimens.

 

Bastug A, Hanifehnezhad A, Tayman C, et al. Virolactia in an Asymptomatic Mother with COVID-19. Breastfeed Med. 2020 Jul 1. PubMed: https://pubmed.gov/32614251. Full-text: https://doi.org/10.1089/bfm.2020.0161

Another case report of a pregnant woman with subclinical COVID-19 whose breast milk sample obtained after delivery tested positive for SARS-CoV-2 by RT-PCR. In addition, although an initial nasopharyngeal swab (NPS) sample from the neonate resulted negative, neonatal NPS, stool, and blood samples obtained after breastfeeding were all positive in real-time RT-PCR assay.

 

Diagnostics

Magleby R, Westblade LF, Trzebucki A, et al. Impact of SARS-CoV-2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients with Coronavirus Disease 2019. Clin Infect Dis. 2020 Jun 30:ciaa851. PubMed: https://pubmed.gov/32603425. Full-text: https://doi.org/10.1093/cid/ciaa851

Viral load matters: admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlated with the risk of intubation and in-hospital mortality. In 678 patients with COVID-19, higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% with a high viral load (Ct < 25; n = 220), 17.6% with a medium viral load (Ct 25-30; n=216), and 6.2% with a low viral load (Ct > 30; n = 242; P < 0.001). The risk of intubation was also higher in patients with a high viral load (29.1%), compared to those with a medium (20.8%) or low viral load (14.9%; P < 0.001). High viral load was independently associated with mortality (adjusted odds ratio 6.05; 95% CI: 2.92-12.52) and intubation (aOR 2.73; 95% CI: 1.68-4.44) in multivariate models.

 

Clinical

Baqui P, Bica I, Marra V, et al. Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study. Lancet Global Health 2020, July 2. Full-text: https://doi.org/10.1016/S2214-109X(20)30285-0

The most extensive study (cross-sectional observational) of COVID-19 hospital survival in Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Survivors were more likely to be younger, be women, and have fewer comorbidities, keeping with worldwide findings. In addition, Pardo ethnicity (mixed race) was the second most important risk factor (after age) for death. The ethnicity effect might be related to differences in susceptibility to COVID-19 and access to health care (including intensive care) across ethnicities.

 

Feaster M, Goh Y-Y. High proportion of asymptomatic SARS-CoV-2 infections in 9 long-term care facilities, Pasadena, California, USA, April 2020. Emerg Infect Dis 2020, Jul 2. Full-text: https://doi.org/10.3201/eid2610.202694

SARS-CoV-2 prevalence in 9 long-term care facilities demonstrated a high proportion (40.7%, 257/631) of asymptomatic infections among residents and staff members. The prevalence of asymptomatic infection differed markedly between facilities: among staff members from 17.4% to 30.6%, among residents from 19.0% to 85.7%.

 

Treatment

Kupferschmidt K. One U.K. trial is transforming COVID-19 treatment. Why haven’t others delivered more results? Science Jul. 2, 2020. Full-text: https://doi.org/10.1126/science.abd6417

Where are the results of the hundreds of clinical trials conducted during the last months? This article describes the challenges that clinical trials are facing world-wide. Some details on WHO’s SOLIDARITY are given. With recruitment running at about 500 patients per week now, SOLIDARITY’s three remaining treatment arms are likely to yield answers “soon” (whatever that means), raising the question of what drugs to test afterward. Some repurposed drugs such as camostat mesylate or favipiravir are still being discussed, but increasingly the attention is turning to monoclonal antibodies, designed to target the virus.