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By Christian Hoffmann &
Bernd S. Kamps

5 August

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Google Translate has an excellent reputation for accuracy, but it isn’t perfect and does make mistakes. So use it with caution. In particular, be careful in relying on Google Translate for any important matter (health, treatment, etc.). In case of doubt, ask your friends.

 

Epidemiology

Sabbadini LL, Romano MC, et al. [First results of the seroprevalence survey  about SARS-CoV-2] (Primi risultati  dell’indagine di sieroprevalenza  sul SARS-CoV-2). Italian Health Ministery and National Statistics Institute 2020, published 3 August. Full-text (Italian): https://www.istat.it/it/files//2020/08/ReportPrimiRisultatiIndagineSiero.pdf

According to a representative study by the Italian Ministry of Health (64,000 participants), 1.5 million people (2.5% of the population) had SARS-CoV-2 antibodies during the study period from May 25 to July 15. This figure is higher than the currently reported 250,000 cases, but far less than an estimate by the UK Imperial College which projected the number of infected people in Italy to be 6 million on 28 March (95% credible interval: 1,932,800 – 15,704,000; see the full-text, published on 30 March). Perhaps to beware of Imperial College projections. The more important message of the Italian study: if these figures are true, the infection fatality rate (IFR, the proportion of deaths among all the infected individuals) in Italy would be 2.3% (35,000 deaths/1,500,000 infections). This is higher than in other European countries and needs to be addressed in future studies.

 

Panovska-Griffiths J, Kerr CC, Stuart RM, et al. Determining the optimal strategy for reopening schools, the impact of test and trace interventions, and the risk of occurrence of a second COVID-19 epidemic wave in the UK: a modelling study. Lancet Child Adolesc Health 2020, August 03, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30250-9

Does anyone doubt this? To prevent a second wave, relaxation of physical distancing, including reopening of schools, must be accompanied by large-scale, population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of diagnosed individuals. The authors estimate for the UK that without these levels of testing and contact tracing, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a second wave that would peak in December 2020 (if schools open full-time in September), having 2.0 – 2.3 times the size of the original COVID-19 wave.

 

Transmission

Macartney K, Quinn HE, Pillbury AJ.  Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study. Lancet Child Adolesc Health, August 03, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30251-0

Transmission in schools may be less frequent than expected. This group has analyzed 15 schools and ten ECEC (early childhood education and care) settings which had children (n=12) or adults (n=15) attending while infectious, with 1,448 contacts monitored. Of these, 633 (44%) had nucleic acid testing or antibody testing, with 18 secondary cases identified (attack rate 1.2%). Five secondary cases (three children; two adults) were identified (attack rate 0.5%; 5/914) in three schools. No secondary transmission occurred in nine of ten ECEC settings among 497 contacts. However, one outbreak in an ECEC setting involved transmission to six adults and seven children (attack rate 35%; 13/37).

 

Valentine R, Valentine D, Valentine JL. Relationship of George Floyd protests to increases in COVID-19 cases using event study methodology. Journal of Public Health, August 5, 2020. Full-text: https://doi.org/10.1093/pubmed/fdaa127

Best author list of the day. Randall, Dawn and Jimmie L. Valentine (from different institutions) show that in 6/8 US cities in which protestors in the tens of thousands were reported, infection rate growth was positive and significant. The Valentines argue that to slow the spread of COVID-19, CDC guidelines must be followed in protest situations. Well, it’s not that easy when you are angry.

 

Immunology

Zhou R, Wang KK, Wong YC, et al. Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. Immunology August 03, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.07.026

More insights on T cell immunity. By investigating 17 acute and 24 convalescent patients, the authors found that acute infection resulted in broad immune cell reduction including T, NK, monocyte and dendritic cells (DC). DCs were significantly reduced with functional impairment. Neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks post symptom onset. These findings provide evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, may contribute to acute COVID-19 pathogenesis.

 

Clinical

Califf RM, Hernandez AF, Landray M, et al. Weighing the Benefits and Risks of Proliferating Observational Treatment Assessments: Observational cacophony, randomized harmony. JAMA. Published online July 31, 2020. Full-text: https://doi.org/10.1001/jama.2020.13319

The authors provide some thoughts on how hundreds of observational studies that have added nothing more than noise, confusion, and false confidence when their findings were widely disseminated by the lay media.

 

Zhao J, Yang Y, Huang H, et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. Clinical Infectious Diseases, August 4, 2020, ciaa1150, https://doi.org/10.1093/cid/ciaa1150.

Among 3700 patients from Wuhan, the risk for infection significantly increased for blood group A (OR 1.3, 95% CI1.1-1.4) and decreased for blood group O (OR 0.7, 95% CI 0.6-0.8). Blood group O was associated with a lower risk of death compared with non-O groups, with an OR of 0.7 (95% CI 0.5-0.9). On the other hand, blood group A was associated with a higher risk of death compared with non-A groups, with an OR of 1.5 (95% CI 1.1-2.0). However, many open questions remain and the authors conclude that it would be premature to use this study to guide clinical practice at this time.

 

Treatment

Fajgenbaum DC, Rader DJ. Teaching Old Drugs New Tricks: Statins for COVID-19? Cell Metabolism August 4, 2020, 32: 145-147. Full-text: https://doi.org/10.1016/j.cmet.2020.07.006

The authors review the literature and argue that, given the association between statin use and improved outcomes in a large observational study of hospitalized COVID-19 patients, but also given the widespread availability, low cost, and safety of statins, this drug class should be further investigated in randomized controlled trials.

 

Robson F, Khan KS, Le TK, et al. Coronavirus RNA proofreading: molecular basis and therapeutic targeting.  Molecular Cell. August 04, 2020. Full-text: https://doi.org/10.1016/j.molcel.2020.07.027

These authors review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. They also consider existing nucleoside analogues and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.

 

Clark KE, Collas O, Lachmann H, et al. Safety of intravenous Anakinra in COVID-19 with evidence of hyperinflammation, a case series. Rheumatol Adv Pract, August 4, 2020. Full-text:  https://doi.org/10.1093/rap/rkaa040

Some more data on anakinra. Four patients with severe COVID-19 infection requiring intensive care admission and ventilatory support are described. Upon commencement of intravenous anakinra, there was subsequent improvement in the patients clinically with reduced ventilatory support and inotropic support, and biochemically, with rapid improvement in inflammatory markers. But again, think about the earlier JAMA comment above (Califf RM et al.)