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By Christian Hoffmann &
Bernd S. Kamps
10 August
Epidemiology
Kalk A, Schultz A. SARS-CoV-2 epidemic in African countries—are we losing perspective? Lancet, August 07, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30563-6
Important comment on modelling studies predicting a huge death toll for some African countries. In the Democratic Republic of the Congo and Malawi, for instance, only 2-3% of the population is older than 65 years. According to the two authors (who work in these countries), the lockdown measures proposed by others do not appear applicable to the African continent and might cause more harm than SARS-CoV-2 itself.
Virology
Wolff G, Limpnes RW, Zevenhoven-Dobbe JC, et al. A molecular pore spans the double membrane of the coronavirus replication organelle. Science 06 Aug 2020: eabd3629. Full-text: https://doi.org/10.1126/science.abd3629
Coronavirus replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored micro-environment for viral RNA synthesis in the infected cell. Using cellular electron cryo-microscopy, the authors visualized a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. Although the exact mode of function of this molecular pore remains to be elucidated, it would clearly represent a key structure in the viral replication cycle that may offer a specific drug target.
Immunology
Grajales-Reyes GE, Colonna M. Interferon responses in viral pneumonias. Science 07 Aug 2020: Vol. 369, Issue 6504, pp. 626-627. Full-text: https://science.sciencemag.org/content/369/6504/626
IFNs are important cytokines of the innate and adaptive immune system and are classified into three main types: I (α or β), II (γ), and III (λ). This perspective summarizes the complexity of IFN responses in SARS-CoV-2 infection. Research is needed to establish whether IFN-λ and type I IFNs have similar effects or whether one is more beneficial or detrimental than the other. It should be conclusively established whether type I IFN responses are augmented in the lungs of COVID-19 patients in contrast to the suppressed type I IFN responses observed in the blood. Further research will be necessary to determine whether suppression of blood type I IFN in critically ill COVID-19 patients is due to the ability of SARS-CoV-2 proteins to interfere with IFN signaling.
Diagnosis
Sapkota D, Søland TM, Galtung HK, et al. COVID-19 salivary signature: diagnostic and research opportunities. J Clin Pathol 2020 Aug 7. Full-text: https://doi.org/10.1136/jclinpath-2020-206834
As a non-invasive approach with possibility for self-collection, saliva collection circumvents to a great extent the limitations associated with the use of nasopharyngeal/oropharyngeal swabs. This review summarizes the clinical and scientific basis for the potential use of saliva for COVID-19 diagnosis and disease monitoring. Additionally, Dipak Sapkota and colleagues discuss saliva-based biomarkers and their potential clinical and research applications related to COVID-19.
Clinical
Lee S, Kim T, Lee E, et al. Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea. JAMA Intern Med, August 6, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.3862
This cohort study included 303 patients in a community treatment center in the Republic of Korea, among them 110 (36.3%) asymptomatic at the time of isolation (21 developed symptoms during isolation). The cycle threshold values of RT-PCR for SARS-CoV-2 (“viral load”) in asymptomatic patients were similar to those in symptomatic patients. Of note, the Ct values from lower respiratory tract specimens tended to decrease more slowly in asymptomatic patients than in symptomatic (including pre-symptomatic) patients.
Collateral
Nicolay N, Mirinaviciute G, Mollet T, et al. Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020. Eurosurveillance August 6, 2020. Volume 25, Issue 31. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.31.2001390
Interesting: The number of measles cases declined in the EU and UK in 2020. Reported cases to The European CDC decreased from 710 to 54 between January and May. However, according to the authors, under-diagnoses and under-reporting during the COVID-19 pandemic should be ruled out before concluding that reduced measles circulation is due to social distancing and any community control measures taken to control COVID-19.
Treatment
Ivashchenko AA, Dmitriev KA, Vostokova NV, et al. AVIFAVIR for Treatment of Patients with Moderate COVID-19: Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin Infect Dis. 2020 Aug 9:ciaa1176. PubMed: https://pubmed.gov/32770240. Full-text: https://doi.org/10.1093/cid/ciaa1176
In May 2020 the Russian Ministry of Health granted fast-track marketing authorization to the RNA polymerase inhibitor favipiravir for the treatment of COVID-19 patients. In the pilot stage of a Phase II/III clinical trial, 60 patients hospitalized with COVID-19 pneumonia were randomized to two different dosing groups or standard of care. Favipiravir enabled SARS-CoV-2 viral clearance in 62.5% of patients within 4 days and was safe and well-tolerated. The proportion of patients who achieved negative PCR on day 5 on both dosing regimens was twice as high as in the control group (p < 0.05).
Hayem G, Huet T, Jouveshomme S, et al. Anakinra for severe forms of COVID-19 – Authors’ reply. Lancet August 07, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30274-5
Discussion about a cohort study on anakinra, an interleukin (IL)-1 receptor antagonist. The authors compared 52 consecutive patients with 44 historical patients. Now, three replies address mainly methodological issues. According to the authors, their study was “not perfect from a statistical point of view… only high-quality randomized trials can avoid confounding factors, but the urgent context of the COVID-19 pandemic means randomized trials are not always appropriate”. However, several randomized trials are underway: on August 10, https://clinicaltrials.gov listed 16 Phase II/III studies.
Xia X, Li K, Wu L, et al. Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion. Blood 2020, 136 (6): 755–759. Full-text: https://doi.org/10.1182/blood.2020007079
Same issue: uncontrolled, retrospective data (but huge numbers). This group presents the results of 1430 patients with severe or critical COVID-19 who received standard treatment only and 138 patients who also received ABO-compatible COVID-19 convalescent plasma (CCP). Despite the higher severity level, only 3 patients (2.2%) died in the CCP group through April 20, reducing the mortality rate compared with that in the standard treatment group (4.1%). However, confounding factors (i.e., biased patient assignments) in this retrospective study could not be ruled out. In addition, complete data on neutralizing antibody titers in CCP units were not available, limiting the power of evaluating the correlation between the quality of donor plasma and efficacy.
Pediatrics
Kim L, Whitaker M, O’Halloran A, et al. Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1–July 25, 2020. MMWR Morb Mortal Wkly Rep. ePub: 7 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6932e3
COVID-NET conducts population-based surveillance for laboratory-confirmed COVID-19–associated hospitalizations in 14 US states. From March 1 to July 25, 576 children hospitalized with COVID-19 were reported to COVID-NET. Although the cumulative COVID-19–associated hospitalization rate among children was low compared with that among adults, weekly hospitalization rates in children increased during the surveillance period. Children can develop severe COVID-19 illness; during the surveillance period, one in three children was admitted to the ICU. Hispanic and black children had the highest rates of COVID-19–associated hospitalization.