Home | TOP 10 | TOP 10 BOOK (PDF)

By Christian Hoffmann &
Bernd S. Kamps

12 August

Transmission

Lednicky JA, Lauzardo M, Fan ZH, et al. Viable SARS-CoV-2 in the air of a hospital room 1 with COVID-19 patients. medRxiv 2020, posted 4 August. Pre-print: https://www.medrxiv.org/content/10.1101/2020.08.03.20167395v1

John A. Lednicky and colleagues isolated viable virus from air samples collected 2 to 4.8 meters away from two COVID-19 patients. The genome sequence of the SARS-CoV-2 strain isolated was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. This paper has not yet been peer-reviewed.

 

Chagla Z, Hota S, Khan S, Mertz D, and the International Hospital and Community Epidemiology Group. Airborne Transmission of COVID-19. Clin Infect Dis 2020, published 11 August. Full-text: https://doi.org/10.1093/cid/ciaa1118

Zain Chagla and colleagues discuss the paper by Morawska L, Milton DK, It is Time to Address Airborne Transmission of COVID-19 (Clin Infect Dis 2020, 6 July). They agree that there is potential for the transmission by aerosols, especially in poorly ventilated indoor crowded environments. However, they argue that the main mode of transmission of SARS-CoV-2 is short range through droplets and close contact. Explore this one-page comment to see how the debate continues.

 

Bigelow BF, Tang O, Toci GR, et al. Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home — Maryland, April 2020. MMWR Morb Mortal Wkly Rep. ePub: 11 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6932e4

Nursing home residents who receive hemodialysis are at higher risk for SARS-CoV-2 infections. Benjamin Bigelow and colleagues investigated a COVID-19 outbreak in a Maryland nursing home. The prevalence of infection among residents undergoing dialysis was 47% (15 of 32) as compared to those not receiving dialysis (16%; 22 of 138) (p < 0.001). The authors recommend strict control practices throughout the dialysis process, e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting.

 

Prevention

Schünemann HJ, Akl EA, Chou R, et al. Use of facemasks during the COVID-19 pandemic. Lancet Respir Med. 2020 Aug 3:S2213-2600(20)30352-0. PubMed: https://pubmed.gov/32758441. Full-text: https://doi.org/10.1016/S2213-2600(20)30352-0

SARS-CoV-2 infected people are infectious for at least 48 h before symptom onset (pre-symptomatic); in addition, some people have only minor symptoms (paucisymptomatic) while others remain entirely asymptomatic. Will face masks protect us? Partly, yes, but will it be worth the public’s money or outweigh any potential harms? It depends, say Holger Schünemann and colleagues. In a setting with high baseline risks, such as health-care workers caring for a superspreading patient with COVID-19, wearing a mask may prevent the infection in up to one out of two health-care workers; consequently, there is a strong recommendation that all such individuals should wear a face mask, despite uncertainty in the evidence. In highly populated areas that have high infection rates—eg, USA, India, Brazil, or South Africa—the use of masks will probably outweigh any potential downsides. Read more about the sometimes difficult choices about the type of face mask, including cost, equity, acceptability, and feasibility.

 

Ebrahim SH, Rahmen NMM, Imtiaz R, et al. Forward planning for disaster-related mass gatherings amid COVID-19. Lancet Planet Health 2020, published 11 August. Full-text: https://doi.org/10.1016/S2542-5196(20)30175-3

Occurrences of extreme humid heat, higher than the optimal human survivability limit of 35° C, have more than doubled in frequency since 1979, leading to an increased frequency of tropical cyclones. Ziad Memish and colleagues now explain that all disasters cause large-scale population movements – making physical distancing in the new COVID-world almost impossible. If you are involved in disaster planning, discover all the details you need to keep in mind.

 

Immunology

Zhang J, Wang X, Xing X, et al. Single-cell landscape of immunological responses in patients with COVID-19. Nat Immunol 2020, published 12 August. Full-text: https://doi.org/10.1038/s41590-020-0762-x

Fu-Sheng Wang and colleagues profiled the immunological response landscape in 13 patients with COVID-19 at single-cell resolution, illustrating the dynamic nature of cellular responses during disease progression. First, patients with COVID-19 showed a concerted and strong IFN-α response, an overall acute inflammatory response and an enhanced migration ability. Second, broad immune activation was observed in patients with COVID-19, evidenced by increased proportions of activated T, pro T and plasma B cells. Third, the proportions of active state T cell clusters were significantly higher in patients with COVID-19 and with a preferential enrichment of effector T cell subsets, such as CD4⁺ effector-GNLY, CD8⁺ effector-GNLY and NKT CD160 cells in moderate patients and an NKT CD56 subset in severe patients. Finally, at the early phase of convalescence, the state of the immune system was not fully restored. How long will it take to achieve full immune recovery after COVID-19?

 

Pathogenesis

Arunachalam PS, Wimmers F, Mok CKP, Perera RAPM, et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science 2020, published 11 August. Full-text: http://doi.org/10.1126/science.abc6261

There is something wrong with our innate immune system responding to SARS-CoV-2. Bali Pulendran and colleagues analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals and found a spatial dichotomy in the innate immune response, characterized by suppression of peripheral innate immunity, in the face of proinflammatory responses reported in the lung. In PBMCs of COVID-19 patients, there was reduced expression of HLA-DR and pro-inflammatory cytokines by myeloid cells, and impaired mTOR signaling and IFN-α production by plasmacytoid DCs. In contrast, there were enhanced plasma levels of inflammatory mediators, including EN-RAGE (S100A12, a biomarker of pulmonary injury), TNFSF14, and oncostatin-M. The authors suggest that these three molecules and their receptors could represent attractive therapeutic targets.

See also the Stanford Press News, 11 August: Study reveals immune-system deviations in severe COVID-19 cases.

 

Vaccine

Mulligan MJ, Lyke KE, Kitchin N, et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020, published 12 August. Full-text: https://doi.org/10.1038/s41586-020-2639-4

Mark Mulligan, Kirsten Lyke, Nicholas Kitchin, Judith Absalon and colleagues report the safety, tolerability, and immunogenicity data from an ongoing study among 45 healthy adults, randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1. BNT162b1, developed by BioNTech and Pfizer, is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD). A clear dose-level response in elicited neutralizing titers was observed after doses 1 and 2 with a particularly steep dose response between the 10 μg and 30 μg dose levels. Geometric mean neutralizing titers reached 1.9- to 4.6-fold that of a panel of COVID-19 convalescent human sera at least 14 days after a positive SARS-CoV-2 PCR. The clinical testing of BNT162b1 is taking place in the context of a broader, ongoing COVID-19 vaccine development program by both companies. That program includes the clinical testing of three additional vaccine candidates, including candidates encoding the full-length spike.

 

Clinical

Uppuluri EM, Shapiro NL. Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis. Am J Health Syst Pharm 2020, published 11 August. Full-text: https://doi.org/10.1093/ajhp/zxaa286

Ellen Uppuluri and Nancy Shapiro report a the case of a 32-year-old, overweight (weight, 90 kg; body mass index, 28) male who was treated for COVID-19 in an emergency department (ED) and discharged home. Twelve days later he was found to have a PE. The authors suggest that non-hospitalized patients with COVID-19 may be at higher risk for VTE than patients with other medical illnesses.

 

Poletti P, Tirani M, Cereda D, et al. Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors, Italy, February to April 2020. Euro Surveill. 2020 Aug;25(31). PubMed: https://pubmed.gov/32762797. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.31.2001383

Piero Poletti, Marcello Tirani and colleagues analyzed 5,484 close contacts of COVID-19 cases in Italy. Infection fatality ratio was 0.43% for individuals younger than 70 years and 10.5% for older individuals. The risk of death after infection was 62% lower in clusters identified after 16 March 2020 and 1.8-fold higher for males.

	Contacts	SARS-CoV-2 positive	Deaths	%
0–19	692	304	0
20–49	1,951	885	0
50–59	1,241	648	3	0.46
60–69	867	494	7	1.42
70–79	485	335	23	6.87
≥ 80	248	158	29	18.35
Male	2,398	1,220	33	2.70
Female	3,086	1,604	29	1.81
Comorbidities
None	122	113	1	0.88
Cardiovascular	350	316	51	16.14
Respiratory	50	49	8	16.33
Oncological	106	92	11	11.96
Diabetes/metabolic	93	79	13	16.46
Unknown	4,947	2,335	9	0.39