Top 10: September 22

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By Christian Hoffmann &
Bernd S. Kamps

 

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22 September

Epidemiology

Mecenas P, Bastos RTDRM, Vallinoto ACR, Normando D. Effects of temperature and humidity on the spread of COVID-19: A systematic review. PLoS One. 2020 Sep 18;15(9):e0238339. PubMed: https://pubmed.gov/32946453. Full-text: https://doi.org/10.1371/journal.pone.0238339

Don’t count on the weather. This systematic review of seventeen studies found that cold and dry conditions were potentiating factors on the spread of the virus. Warm and wet climates seem to reduce the spread of COVID-19. However, these variables alone could not explain most of the variability in disease transmission. Therefore, the countries most affected by the disease should focus on health policies, even with climates less favourable to the virus.

 

Immunology

Busch MH, Timmermans SAMEG, Nagy M, et al. Neutrophils and Contact Activation of Coagulation as Potential Drivers of Covid-19. Circulation. 2020 Sep 18. PubMed: https://pubmed.gov/32946302. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050656

Pieter van Paassen and colleagues from Maastricht/Netherlands have performed a comprehensive analysis on the intrinsic pathway of coagulation to characterize its role in COVID-19. By simultaneously studying potential triggers of the intrinsic pathway in 228 patients, the authors were able to identify neutrophils, neutrophil extracellular traps (NETs), and complement activation as potential drivers of this complex immuno-thrombotic disease. This indicates that hypercoagulability and thrombotic events are driven by NETosis, contact activation, and complement. The triangular relationship with its multiple amplifying feedback loops urges for therapeutic multiple-target strategies to dampen effectively the immuno-thrombotic response.

 

Peiris M, Leung GM. What can we expect from first-generation COVID-19 vaccines? Lancet September 21, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31976-0

Not so much. In their important comment, Malik Peiris and Gabriel M Leung suggest that we cannot assume COVID-19 vaccines, even if shown to be effective in reducing severity of disease, will reduce virus transmission to a comparable degree. The notion that COVID-19-vaccine-induced population immunity will allow a return to pre-COVID-19 “normalcy” might be based on illusory assumptions.

 

Saad-Roy M, Wagner CE, Baker RE, et al. Immune life history, vaccination, and the dynamics of SARS-CoV-2 over the next 5 years. Science 21 Sep 2020: eabd7343. Full-text: https://doi.org/10.1126/science.abd7343

But let’s hope. Modelling different protective efficacy and duration of the adaptive immune response to SARS-CoV-2, as well as its interaction with vaccines and nonpharmaceutical interventions, this group from Princeton found that variations in the immune response to primary SARS-CoV-2 infections and a potential vaccine could lead to dramatically different immune landscapes and burdens of critically severe cases, ranging from sustained epidemics to, attention!, near elimination. According to these models, even with imperfect vaccinal immunity and moderate vaccination rates, a vaccination may accelerate pandemic control.

 

Diagnostics

Patel MM, Thornburg NH, Stubblefield WB, et al. Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Personnel in Nashville, Tennessee. JAMA September 17, 2020. Full-text: https://doi.org/10.1001/jama.2020.18796

Your COVID pass expires after a few weeks: among 19 health care workers who had anti–SARS-CoV-2 antibodies detected at baseline, 8 (42%) had antibodies that persisted above the seropositivity threshold at 60 days, whereas 11 (58%) became seronegative. The consistency in decline in the signal-to-threshold ratio regardless of the baseline ratio and a higher proportion of asymptomatic participants becoming seronegative support the interpretation as a true decline over a 2-month period rather than an artifact of assay performance.

 

Clinical

Miller J, Fadel RA, Tang A, et al. The Impact of Sociodemographic Factors, Comorbidities and Physiologic Response on 30-day Mortality in COVID-19 Patients in Metropolitan Detroit. Clin Infect Dis. 2020 Sep 18:ciaa1420. PubMed: https://pubmed.gov/32945856. Full-text: https://doi.org/10.1093/cid/ciaa1420

In this large cohort of 3,633 COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Of note, disparities in income or source of health insurance were not associated with outcomes.

 

Neilan AM, Losina E, Bangs AC, et al. Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts. Clin Infect Dis. 2020 Sep 18:ciaa1418. PubMed: https://pubmed.gov/32945845. Full-text: https://doi.org/10.1093/cid/ciaa1418

Anne M. Neilan and colleagues projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model. Four testing strategies were compared: 1) PCR testing only patients with severe/critical symptoms warranting hospitalization; 2) PCR for any COVID-19-consistent symptoms (symptomatic), with self-isolation if positive; 3) Symptomatic and one-time PCR for the entire population; and, 4) Symptomatic with monthly re-testing for the entire population. Testing people with any COVID-19-consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.

 

Marinho PM, Nascimento H, Marcos AAA, Romano AC, Belfort R Jr. Seeking clarity on retinal findings in patients with COVID-19 – Authors’ reply. Lancet. 2020 Sep 19;396(10254):e40. Full-text: https://doi.org/10.1016/S0140-6736(20)31912-7

Paula M. Marinho and colleagues reply to major concerns (5 letters) that their initial reports on retinal findings in COVID-19 patients (hyper-reflective lesions at the level of the ganglion cell and inner plexiform layers) were, in fact, cuts through normal retinal blood vessels. To ensure that this was not the case, the authors have excluded vertical optical coherence tomography (OCT) scans and used only horizontal scans to avoid vessel crossings. Since their initial report, they have also examined more than 150 patients, demonstrating an absence of blood flow within the retinal lesions of “many”patients, differentiating these lesions from blood vessels with active blood flow.

 

Treatment

Gentrey CA, Humphrey MB, Thind SK, et al. Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study. Lancet Rheumatology September 21, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30305-2

Did you expect that patients with rheumatological conditions receiving chronic hydroxychloroquine therapy would be at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine? No? Then you are right. The incidence did not differ between patients with or without hydroxychloroquine in this large cohort (31 of 10,703 vs 78 of 21,406; odds ratio 0.79, 95% CI 0.52–1.20, p=0.27).

 

Pediatrics

Flaherman VJ, Afshar Y, Boscardin J, et al. Infant Outcomes Following Maternal Infection with SARS-CoV-2: First Report from the PRIORITY Study. Clin Infect Dis. 2020 Sep 18:ciaa1411. PubMed: https://pubmed.gov/32947612. Full-text: https://doi.org/10.1093/cid/ciaa1411

Among 263 initial infants enrolled in the PRIORITY study, adverse outcomes, including preterm birth, NICU admission, and respiratory disease did not differ between those born to mothers testing positive for SARS-CoV-2 (n=184) and those born to mothers testing negative (n=79). No pneumonia or lower respiratory tract infection was reported through 6-8 weeks of age. Among infants born to mothers who tested positive for SARS-CoV-2, the estimated incidence of a positive infant was low at 1.1% (0.1%, 4.0%), and infants had minimal symptoms. Overall, these results are reassuring and suggest that infants born to mothers infected with SARS-CoV-2 generally do well in the first 6-8 weeks after birth.