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By Christian Hoffmann &
Bernd S. Kamps
13 June
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Epidemiology
Walker PG, Whittaker C, Watson OJ, et al. The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries. Science 12 Jun 2020. Full-text: https://DOI.ORG/10.1126/science.abc0035
An in-depth analysis of the potential impact of the pandemic in low- and middle-income countries (LMIC). The analysis gives insight into how differences in demography, social structure and health care availability and quality combine and potentially influence the impact of measures that can help reduce the spread of the virus. However, the bottom line is: We don’t know yet. On one hand, we have an overall younger population and a shorter time for lockdown measures to be in place in LMIC. On the other hand, there is a higher burden of infectious diseases such as AIDS and TB already, and of poverty-related determinants of poorer health outcomes such as malnutrition. There is also a more persistent spread to older age categories (higher levels of household-based transmissions) and poorer quality health care and lack of health care capacity.
Oreshkova N, Molenar RJ, Vremen S. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Eurosurveillance 2020, June 11. Volume 25, Issue 23. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.23.2001005
Despite a law approved by the Dutch parliament in 2012 that will ban mink farming as of 2024 for ethical reasons, there are still around 125 mink farms in the Netherlands, with an average of 5,000 female breeding animals. In 2019, 4 million minks were “produced”. This article describes several outbreaks on these farms. Detection of viral RNA in the airborne inhalable dust clearly suggests dust and/or droplets as means of transmission between the minks and occupational risk of exposure for the workers on the farms. On 3 June, the Dutch Ministry of Agriculture decided to cull all minks of SARS-CoV-2-infected farms, starting on 5 June. This may be the right time to speed up the final ban.
Immunology
Major J, Crotta S, Llorian M, et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science 11 Jun 2020. Full-text: https://DOI.ORG/10.1126/science.abc2061
Key message: Interferon may be helpful during early infection and harmful at later stages. IFN-λ mainly signals in epithelia, inducing localized antiviral immunity, and has a key role in the reduction of epithelial proliferation and differentiation during lung repair. In animal and cell experiments, the authors show that IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity and susceptibility to bacterial superinfections. Excessive or prolonged IFN production may aggravate viral infection by impairing lung epithelial regeneration.
Broggi A, Ghosh S, Sposito B, et al. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science 11 Jun 2020. Full-text: https://DOI.ORG/10.1126/science.abc3545
Same direction as above: Detrimental activities of IFN-λ only occur upon chronic exposure and in the presence of tissue damage. In mice, IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA-induced barrier damage, causing susceptibility to lethal bacterial superinfections.
Diagnostics
Caini S, Bellerba F, Corso F, et al. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications. Eurosurveillance 2020, June 11. Volume 25, Issue 23. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.23.2000980
This review of the diagnostic accuracy of SARS-CoV-2 serological tests includes 9 studies, using different test kits. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimates were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, the positive predictive value would be ≤ 88%. According to the authors, serological tests should be used for prevalence surveys only in hard-hit areas.
Hung IF, Cheng VC, Li X. SARS-CoV-2 shedding and seroconversion among passengers quarantined after disembarking a cruise ship: a case series. Lancet Inf Dis, June 12, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30364-9
Among 215 adult (≥ 18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship and who had been found to be PCR-negative before disembarking, 9 became positive during quarantine. Those with evidence of pneumonia on imaging tended to have an increased antibody response. However, positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients.
Clinical
Sakurai A, Sasaki T, Kato S, et al. Natural History of Asymptomatic SARS-CoV-2 Infection. NEJM June 12, 2020. Full-text: https://DOI.ORG/10.1056/NEJMc2013020
More on asymptomatic infection: The authors followed 90 persons from the cruise ship Diamond Princess who were asymptomatic at the time of the positive PCR test and remained so until the resolution of infection (as determined by two consecutive negative PCR tests). 27% had coexisting medical conditions. The median time between the first positive PCR test result (either on the ship or at the hospital) and the first of the two serial negative PCR results was 9 days (range, 3 to 21), and the cumulative percentages of persons with resolution of infection 8 and 15 days after the first positive PCR were 48% and 90%, respectively.
Tabata S, Imai K, Kawano S, et al. Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis. Lancet Inf Dis 2020, June 12. Full-text: https://doi.org/10.1016/S1473-3099(20)30482-5.
Among 104 people from the Diamond Princess cruise ship who were admitted to a Tokyo hospital, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period.
Solomon IH, Normandin E, Bhattacharyya B, et al. Neuropathological Features of Covid-19. NEJM June 12, 2020. Full-text: https://DOI.ORG/10.1056/NEJMc2019373
Histopathological examination of brain specimens obtained from 18 patients who died 0 to 32 days after the onset of symptoms showed only hypoxic changes and did not show encephalitis or other specific brain changes referable to the virus. The virus was detected at low levels in 6 brain sections obtained from 5 patients; it remains to be seen whether this was due to in situ virions or viral RNA from blood.
Wright Hr KP, Linton SK, Withrow D. Sleep in University Students Prior to and During COVID-19 Stay-at-Home Orders. Current Biology, June 10, 2020 Full-text: https://doi.org/10.1016/j.cub.2020.06.022
Good to know: during lockdown, they sleep better. This ground-breaking study investigated sleep behaviors prior to and during Stay-at-Home orders in 139 university students. During Stay-at-Home, nightly time in bed devoted to sleep increased by 30 min during weekdays and by 24 mins on weekends and regularity of sleep timing improved by 12 min. Sleep timing became later by 50 min during weekdays and 25 min on weekends, and thus the difference between weekend and weekday sleep timing decreased—hence reducing the amount of social jetlag. A subsequent study on changes in breakfast behaviors is eagerly awaited (proposed hypothesis: less coffee, more jam).