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By Christian Hoffmann &
Bernd S. Kamps

30 May

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Summary

First, investigate the introduction and early spread of SARS-CoV-2 in the New York City area; analyze the stay-at-home orders in Colorado, Minnesota, Ohio, and Virginia; and characterize the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2.

Afterwards, examine hospitalization and mortality among black patients and white patients in a cohort of 3,481 patients in Louisiana; write a review about neuropathogenesis and neurologic manifestations of coronaviruses; present magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia; and compare the clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease.

Finally, list the risk factors associated with COVID-19 disease severity in patients with cancer; describe mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection; and discuss with your colleagues the use of anakinra for severe forms of COVID-19.

 

Epidemiology

Gonzalez-ReicheAS, Hernandez MM, Sullivan MJ, et al. Introductions and early spread of SARS-CoV-2 in the New York City area. Science 29 May 2020: eabc1917. Full-text: https://doi.org/10.1126/science.abc1917

A first analysis of the SARS-CoV-2 viral genotypes collected from patients seeking medical care in the New York City metropolitan area. Main message: The NYC epidemic has been mainly sourced from untracked transmission between the US and Europe, with limited evidence of direct introductions from China where the virus originated. Isolates were distributed throughout the phylogenetic tree; consistent with multiple independent introductions.

 

Sen S, Karaca-Mandic P, Georgiou A. Association of Stay-at-Home Orders With COVID-19 Hospitalizations in 4 States. JAMA May 27, 2020. Full-text: https://10.1001/jama.2020.9176

Staying at home works. In 4 US states (Colorado, Minnesota, Ohio, and Virginia) with stay-at-home orders, cumulative hospitalizations for COVID-19 deviated from projected best-fit exponential growth rates after these orders became effective. The deviation started 2 to 4 days sooner than the median effective date of each state’s order and may reflect the use of a median incubation period for symptom onset and time to hospitalization to establish this date.

 

Virology

Peng Q, Peng R, Yuan B, et al. Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2. Cell Reports. May 30, 2020. Full-text: https://10.1016/j.celrep.2020.107774

The replication of coronavirus is operated by a set of non-structural proteins (nsps) encoded by the open-reading frame 1a (ORF1a) and ORF1ab in its genome, which are initially translated as polyproteins followed by proteolysis cleavage for maturation. These proteins assemble into a multi-subunit polymerase complex to mediate the transcription and replication of viral genome. Among them, nsp12 is the catalytic subunit with RNA-dependent RNA polymerase (RdRp) activity. The nsp12 itself is capable of conducting polymerase reaction with extremely low efficiency, whereas the presence of nsp7 and nsp8 cofactors remarkably stimulates its polymerase activity. Using cryo-EM, near-atomic resolution structure of SARS-CoV-2 nsp12-nsp7-nsp8 core polymerase complex is described.

 

Clinical

Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med. 2020 May 27. PubMed: https://pubmed.gov/32459916. Full-text: https://doi.org/10.1056/NEJMsa2011686

It’s poverty and obesity, but not race. In a large cohort of 3,481 patients in Louisiana, 76.9% of the patients who were hospitalized with COVID-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the population. Of note, black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

 

Zubair AS, McAlpine LS, Gardin T, et al. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurology May 29, 2020. Full-text: https://10.1001/jamaneurol.2020.2065

Viral neuro-invasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. This review summarizes available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system.

 

Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurology May 29, 2020.  Full-text: https://10.1001/jamaneurol.2020.2125

Interesting case report, describing in vivo brain alteration during COVID-19. A patient with COVID-19 showed a signal alteration compatible with viral brain invasion in a cortical region (ie, posterior gyrus rectus). Slight and reversible olfactory bulb changes were also seen.

 

Yang R, Gui X, Xiong Y, et al. Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China. JAMA Netw Open, May 27 2020. Full-text: https://10.1001/jamanetworkopen.2020.10182i

Case series, including carefully selected data for 78 patients (33 asymptomatic) from 26 cluster cases of exposure to the Hunan seafood market or close contact with other patients with COVID. Asymptomatic patients were younger and had a median shorter duration of viral shedding from nasopharynx swabs (median duration, 8 days vs 19 days)

 

Comorbidities

Tian J, Yuan X, Xiao J, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncology 2020, May 29. Full-text: https://10.1016/S1470-2045(20)30309-0

232 COVID-19 patients with cancer and were compared with 519 matched patients without cancer. Patients with cancer were more likely to have severe COVID-19 (64% versus 32%). Risk factors (of those well-known) for severe disease were advanced tumour stage (OR 2.60), elevated tumour necrosis factor α (1.22), elevated N-terminal pro-B-type natriuretic peptide (1.65).

 

COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet May 29, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31182-X

This large cohort includes 1128 patients who had surgery between Jan 1 and March 31, 2020, among them 835 (74%) emergency surgery and 280 (25%) elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26%) patients. 30-day mortality was 24% and pulmonary complications occurred in 577 (51%). In adjusted analyses, 30-day mortality was associated with male sex (Odds Ratio 1.75), age 70 years or older (2.30), ASA grades 3–5 versus grades 1–2 (2.35), malignant versus benign (1.55), emergency versus elective surgery (1.67), and major versus minor surgery (1.52).

 

Treatment

Huet T, Beaussier H, Voisin O, et al. Anakinra for severe forms of COVID-19: a cohort study.Lancet Rheumatol 2020, May 29, 2020. https://doi.org/10.1016/S2665-9913(20)30164-8

This study from Paris compared 52 consecutive patients treated with anakinra with 44 historical patients. Admission to the ICU for invasive mechanical ventilation or death occurred in 25% patients in the anakinra group and 73% patients in the historical group. Treatment effect of anakinra remained significant in the multivariate analysis. Controlled trials are needed.