Top 10: July 17

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By Christian Hoffmann &
Bernd S. Kamps

17 July

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Immunology

Lynch KL, Whitman JD, Lacanienta NP, et al. Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity. Clin Infect Dis. 2020 Jul 14. PubMed: https://pubmed.gov/32663256. Full-text: https://doi.org/10.1093/cid/ciaa979

Using a high-throughput quantitative IgM and IgG assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein, the authors evaluated antibody kinetics and correlation between magnitude of the response and disease severity in a total of 533 sera samples from 94 acute and 59 convalescent COVID-19 patients. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the ICU for all time intervals between days 6 and 20 for IgM, and all intervals after 5 days for IgG.

 

Akbar AN, Gilroy DW. Aging immunity may exacerbate COVID-19. Science 17 Jul 2020: Vol. 369, Issue 6501, pp. 256-257. Full-text: https://doi.org/10.1126/science.abb0762

Nice brief overview on how “inflammaging”, a common denominator of age-associated frailty, may contribute to the severe COVID-19 course in older people. One hypothesis is that pre-existing inflammatory cells, including senescent populations and adipocytes, create the inflammaging phenotype that amplifies subsequent inflammatory events. Nevertheless, high amounts of inflammation alone do not explain the devastating tissue destruction and it may be that age-associated changes in T cells have a role in the immunopathology.

 

Transmission

Hendrix MJ, Walde C, Findley K, Trotman R. Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy — Springfield, Missouri, May 2020. MMWR Morb Mortal Wkly Rep. 14 July 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6928e2

Have we ever mentioned masks? Among 139 clients exposed to two symptomatic hair stylists with confirmed COVID-19 while both the stylists and the clients wore face masks, not a single symptomatic secondary case was observed; among 67 clients tested for SARS-CoV-2, all tests were negative. At least one hair stylist was infectious: all four close household contacts (presumably without masks) became ill.

 

Wang X, Ferro EG, Zhou G, Hashimoto D, Bhatt DL. Association Between Universal Masking in a Health Care System and SARS-CoV-2 Positivity Among Health Care Workers. JAMA. 2020 Jul 14. PubMed: https://pubmed.gov/32663246. Full-text: https://doi.org/10.1001/jama.2020.12897

Again, universal masking: in March 2020, the Mass General Brigham, the largest health care system in Massachusetts (12 hospitals, > 75,000 employees), implemented universal masking of all HCWs and patients with surgical masks. During the preintervention period, the SARS-CoV-2 positivity rate increased exponentially, with a case doubling time of 3.6 days. During the intervention period, the positivity rate decreased linearly from 14.65% to 11.46%, with a weighted mean decline of 0.49% per day and a net slope change of 1.65% additional decline per day compared with the preintervention period.

 

Contejean A, Leporrier J, Canouï E, et al. Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris. Clin Infect Dis. 2020 Jul 15:ciaa977. PubMed: https://pubmed.gov/32663849. Full-text: https://doi.org/10.1093/cid/ciaa977

This prospective study compared a 1,500-bed adult and a 600-bed pediatric setting of a university hospital located in central Paris. From February 24th until April 10th, 2020, all symptomatic HCW were screened. Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p = 0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p = 0.046). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase in preventive measures (including universal medical masking and PPE). Residual transmissions were related to exposures with undiagnosed patients or colleagues but not to contacts with children attending out-of-home care facilities.

 

Brooks JT, Butler JC, Redfield RR. Universal Masking to Prevent SARS-CoV-2 Transmission—The Time Is Now. JAMA July 14, 2020. Full-text: https://doi.org/10.1001/jama.2020.13107

See title. Data is clear now. First, public health officials need to ensure that the public understands clearly when and how to wear cloth face coverings properly. Second, innovation is needed to extend physical comfort and ease of use. Third, the public needs consistent, clear, and appealing messaging that normalizes community masking. According to the authors, broad adoption of cloth face coverings is a civic duty, a small adaption in our daily lives reliant on a highly effective low-tech solution that can help turn the tide.

 

Clinical

Perez-Saez J, Lauer SA, Kaiser L. Serology-informed estimates of SARS-CoV-2 infection fatality risk in Geneva, Switzerland. Lancet July 14, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30584-3

This important study has estimated age-specific infection fatality risks (IFRs) for Geneva, Switzerland, using population-based seroprevalences. After accounting for demography and age-specific seroprevalence, the population-wide IFR was 0.64% (0.38–0.98). Check your age: IFR differed markedly between the age groups. IFR was only 0.0092% (95% between 0.0042–0.016) for individuals aged 20–49 years, 0.14% (0.096–0.19) for those aged 50–64 years but 5.6% (4.3–7.4) for those aged 65 years and older.

 

Buscarini E, Manfredi G, Brambilla G, et al. GI symptoms as early signs of COVID-19 in hospitalised Italian patients. Gut. 2020 Aug;69(8):1547-1548. PubMed: https://pubmed.gov/32409587 . Full-text: https://doi.org/10.1136/gutjnl-2020-321434

Among 411 consecutive COVID-19 patients, 42 (10.2%) reported GI symptoms including nausea (4.3%), vomiting (3.8%), diarrhea (3.6%) or abdominal pain (1.2%). GI symptoms had a mean onset of 4.9 ± 4.4 days before admission. Absence of cough was reported in 35/42 (83%) patients with GI symptoms. According to the authors, their findings of these 10% of COVID-19 patients confirms that the prevalence of GI symptoms at onset “is not negligible”. That’s probably why this was published in Gut.

 

Severe COVID-19

Grasselli G, Greco M, Zanella A, et al. Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy.  JAMA Intern Med July 15, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.3539

If you are in the ICU, it’s 50/50. In this large cohort study of 3,988 critically ill patients, most required invasive mechanical ventilation, and mortality rate was high. In the subgroup of the first 1715 patients, 915 patients died in the hospital for an overall hospital mortality of (53.4%).

 

Gupta S, Hayek SS, Wang W, et al. Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US. JAMA Intern Med July 15, 2020. –Full-text: https://doi.org/10.1001/jamainternmed.2020.3596

But it depends where you are. In this US cohort of 2,215 adults with COVID-19 who were admitted to ICUs at 65 sites, 784 (35.4%) died within 28 days. However, mortality showed an extremely wide variation among hospitals (range, 6.6%-80.8%). Factors associated with death included older age, male sex, obesity, coronary artery disease, cancer, acute organ dysfunction, and, importantly, admission to a hospital with fewer intensive care unit beds. Patients admitted to hospitals with fewer than 50 ICU beds versus at least 100 ICU beds had a higher risk of death (OR 3.28; 95% CI, 2.16-4.99).