Top 10: April 25

<<< April 2020

By Christian Hoffmann &
Bernd S. Kamps

Epidemiology

Gatto M, Bertuzzo E, Mari L, et al. Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures. Proc Natl Acad Sci U S A. 2020 Apr 23. pii: 2004978117. PubMed: https://pubmed.gov/32327608 . Full-text: https://doi.org/10.1073/pnas.2004978117

Complex models from Italy, quantifying the effect of local containment measures. Bottom line: The sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Models unquestionably support drastic governmental decisions as made in Italy.

 

Transmission

Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329971 . Full-text: https://doi.org/10.1056/NEJMoa2008457

The next outbreak in King County, Washington. A skilled nursing facility facing rapid and widespread transmission of the virus, leading to 17 deaths in 57 residents. Of note 27/48 with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focussing solely on symptomatic residents are not sufficient! Test them all, immediately!

 

Tobias A, Molina T. Is temperature reducing the transmission of COVID-19 ? Environ Res. 2020 Apr 18;186:109553. PubMed: https://pubmed.gov/32330766 . Full-text: https://doi.org/10.1016/j.envres.2020.109553

Measuring temperature’s impact on transmission rates is almost impossible in such a dynamic pandemic. Authors have made this heroic attempt, showing that the number of diagnosed cases may increase below a maximum temperature of 10 °C and linearly decreasing afterward. Thus, the arrival of summer could reduce the transmission of the COVID-19. However, this only a first clue which has to be confirmed.

 

Diagnostics

Torres R, Rinder HM. Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now? Am J Clin Pathol. 2020 Apr 23. pii: 5823978. PubMed: https://pubmed.gov/32322898 . Full-text: https://doi.org/10.1093/ajcp/aqaa071

Brief but excellent review on the pitfalls and problems of antibody tests. At present, a positive antibody result does not guarantee non-infectious status nor immunity. What about asymptomatic or minimally symptomatic persons? The molecular heterogeneity of SARS-CoV-2 subtypes, imperfect performance of available tests and cross-reactivity with seasonal CoVs are discussed.

 

Xiao AT, Tong YX, Zhang S. Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Clin Infect Dis. 2020 Apr 19. pii: 5822175. PubMed: https://pubmed.gov/32306036 . Full-text: https://doi.org/10.1093/cid/ciaa460

 

Dynamics profile of SARS-CoV-2 shedding from 56 recovered patients. The negative results of RT-PCR test for SARS-CoV-2 (throat or deep nasal cavity swab samples) began dominant from week 4 after onset of symptoms and by the end of follow-up (6 weeks), all results of RT-PCR test were negative.

Yongchen Z, Shen H, Wang X, et al. Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients. Emerg Microbes Infect. 2020 Apr 20:1-14. PubMed: https://pubmed.gov/32306864 . Full-text: https://doi.org/10.1080/22221751.2020.1756699

 

Do asymptomatic individuals develop antibodies? Serial investigation on 21 individuals from Jiangsu Province, including 17 COVID-19 patients and 5 asymptomatic carriers, using gold immunochromatography assay supplied by Innovita (China). All of 17 symptomatic patients were seropositive within week 6. Only 1/5 asymptomatic cases generated SARS-CoV-2 specific antibody responses within the first 4 weeks.

 

Comorbidities

Pereira MR, Mohan S, Cohen DJ, et al. COVID-19 in Solid Organ Transplant Recipients: Initial Report from the US Epicenter. Am J Transplant. 2020 Apr 24. PubMed: https://pubmed.gov/32330343 . Full-text: https://doi.org/10.1111/ajt.15941

The first larger cohort of COVID-19 in transplant recipients. Of 90 patients (median age of 57 years), 46 were kidney recipients, 17 lung, 13 liver, 9 heart and 5 dual-organ transplants. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU), indicating that transplant recipients appear to have more severe outcomes.

 

Akalin E, Azzi Y, Bartash B. Covid-19 and Kidney Transplantation. N Engl J Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329975 . Full-text: https://doi.org/10.1056/NEJMc2011117

Single center experience with 36 kidney-transplant recipients. Patients appear to have less fever as an initial symptom, lower CD3/4/8 cell counts and more rapid clinical progression: after 21 days, 10 have died.

 

French JA, Brodie MJ, Caraballo R, et al. Keeping people with epilepsy safe during the Covid-19 pandemic. Neurology. 2020 Apr 23. pii: WNL.0000000000009632. PubMed: https://pubmed.gov/32327490 . Full-text: https://doi.org/10.1212/WNL.0000000000009632

Some helpful recommendations on how to modify clinical care for people with epilepsy and what general advice should be given to these patients during this crisis.

 

Treatment

Dai W, Zhang B, Su H, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020 Apr 22. pii: science.abb4489. PubMed: https://pubmed.gov/32321856 . Full-text: https://doi.org/10.1126/science.abb4489

More on a key enzyme, SARS-CoV-2’s main protease (Mpro). Authors synthesized two lead compounds (11a and 11b) targeting Mpro, exhibiting good inhibitory activity, good PK properties and low toxicity in animal experiments. Pre-clinical.