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By Christian Hoffmann &
Bernd S. Kamps
9 June
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Epidemiology
Flaxman S, Mishra S, Gandy A, et al. Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe. Nature. 2020 Jun 8. PubMed: https://pubmed.gov/32512579. Full-text: https://doi.org/10.1038/s41586-020-2405-7
This world-leading group of epidemiologists and statisticians estimated the total infection rates across 11 European countries. Main results: between 12 and 15 million individuals have been infected with SARS-CoV-2 up to May 4th, representing between 3.2% and 4.0% of the population. Percentages of total population infected were for Austria 0.76% (0.59% – 0.98%), Belgium 8.0 % (6.1% – 11%), Denmark 1.0% (0.81% – 1.4%), France 3.4% (2.7% – 4.3%), Germany 0.85% (0.66% – 1.1%), Italy 4.6% (3.6% – 5.8%), Norway 0.46% (0.34% – 0.61%), Spain 5.5% (4.4% – 7.0%), Sweden 3.7% (2.8% – 5.1%), Switzerland 1.9% (1.5% – 2.4%) and United Kingdom 5.1% (4.0% – 6.5%). Results also showed that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission.
Deng X, Gu W,Federman S, et al. Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California. Science 08 Jun 2020. Full-text: https://doi.org/10.1126/science.abb9263
Detective work, analysing the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with a lack of predominant lineage, and limited transmission between communities.
Immunology
Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med June 05, 2020. Full-text: https://doi.org/10.1016/j.xcrm.2020.100040
A robust humoral immune response occurs early during severe or moderate COVID-19 infections: in this cross-sectional study of 44 hospitalized COVID-19 patients, receptor-binding domain (RBD)-specific IgG responses became detectable in all patients 6 days after PCR confirmation. Neutralizing antibody titers were detectable in 40/44 cases, mostly by 20 days of symptom onset. Of note, RBD-specific IgG titers seemed to correlate with the neutralizing potency, indicating that RBD-specific IgG titers could be used as a surrogate of neutralization activity against SARS-CoV-2 infection.
Seydoux E, Homad LJ, MacCamy AJ, et al. Analysis of a SARS-CoV-2 infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation. Immunity June 05, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.06.001
The authors isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject. Main findings: The 45 S-specific monoclonal antibodies generated had undergone minimal somatic mutation, with limited clonal expansion. Most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and targeted epitopes outside the RBD. Neutralizing antibodies targeting the interaction of the S protein with ACE2 were minimally mutated.
Gutierrez L, Beckford J, Alachkar H. Deciphering the TCR repertoire to solve the COVID-19 mystery. Trends Pharmacol Sci. June 03, 2020. Full-text: https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(20)30130-9
Outstanding article on unresolved questions. Why do some patients develop severe disease, while others do not; and what roles do genetic variabilities play in the individual immune response to this viral infection? The authors discuss the critical role T cells play in the orchestration of the antiviral response underlying the pathogenesis of COVID-19.
Transmission
Matson MJ, Yinda CK, Seifert SN, et al. Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum. Emerg Infect Dis. 2020 Jun 8;26(9). PubMed: https://pubmed.gov/32511089. Full-text: https://doi.org/10.3201/eid2609.202267
Environmental conditions affect the stability of the virus in nasal mucus and sputum. The virus is more stable at low temperature and low humidity conditions, whereas warmer temperatures and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.
Diagnostics
Theel ES, Harring J, Hilgart H, Granger D. Performance Characteristics of Four High-Throughput Immunoassays for Detection of IgG Antibodies against SARS-CoV-2. J Clin Microbiol. 2020 Jun 8:JCM.01243-20. PubMed: https://pubmed.gov/32513859. Full-text: https://doi.org/10.1128/JCM.01243-20
Head-to-head comparison of four high-throughput, commercially available anti-SARS-CoV-2 IgG serologic tests from Abbott Laboratories, Epitope Diagnostics Inc, Euroimmun, and Ortho-Clinical Diagnostics, using serially collected acute and convalescent sera from both hospitalized patients and out-patients with RT-PCR confirmed COVID-19. All four immunoassays performed similarly with respect to sensitivity in COVID-19 hospitalized patients, and except for the Epitope assay, also in individuals with milder forms of the infection. The Abbott and Ortho-Clinical immunoassays provided the highest overall specificity, of over 99%.
Severe COVID-19
Carsana L, Sonzogni A, Nasr A, et al. Pulmonary post-mortem findings in a series of COVID-19 cases. Lancet 2020, June 08. Full-text: https://doi.org/10.1016/S1473-3099(20)30434-5
Lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy were analyzed. The predominant pattern was diffuse alveolar damage, as described in patients infected with SARS and MERS. Hyaline membrane formation and pneumocyte atypical hyperplasia were frequent. However, the presence of platelet–fibrin thrombi in small arterial vessels was consistent with coagulopathy, which appears to be common in patients with COVID-19.
Treatment
Tonn T, Corman VM, Johnsen M, et al. Stability and neutralising capacity of SARS-CoV-2-specific antibodies in convalescent plasma. Lancet Microbe 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30037-9
How stable are antibodies that are found in convalescent plasma? Very stable. Pathogen inactivation (using psoralen and UV light) did not impair the stability and neutralising capacity of SARS-CoV-2-specific antibodies that was also preserved at 100% when the plasma was shock frozen at −30°C after pathogen-inactivation or stored as liquid plasma for up to 9 days.
Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19. Med 2020, June 05, 2020. Full-text: https://doi.org/10.1016/j.medj.2020.06.001
A total of 807 COVID-19 patients hospitalized in US Veterans Administration medical centers in March and April were classified based on their exposure to HCQ or with azithromycin (HCQ+AZ) or no HCQ as treatments. Compared to the no-HCQ group, after propensity score adjustment for clinical characteristics, the risk of death from any cause was higher in the HCQ group (adjusted hazard ratio (1.83; 95% CI, 1.16 to 2.89) but not in the HCQ+AZ group (1.31, 95% CI, 0.80 to 2.15). Both the propensity score-adjusted risks of mechanical ventilation and death after mechanical ventilation were not significantly different in the two HCQ groups, compared to the no HCQ group.