Top 10: August 3

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By Christian Hoffmann &
Bernd S. Kamps

3 August

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<<< 007 | Summer Picture 008. Since 19 July, we have been preparing the Top 10 from a European beach location. While the friends enjoy the beach, we write the daily summaries.


Pham QT, Rabaa MA, Duong HL, et al. The first 100 days of SARS-CoV-2 control in Vietnam. Clin Infect Dis 2020, published 1 August. Full-text:

One hundred days after the first SARS-CoV-2 case was reported in Vietnam on January 23rd, 270 cases were confirmed, with no deaths. Duc Anh Dang and colleagues describe the national control measures and conclude that Vietnam controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission. A lesson for the world.



Szablewski CM, Chang KT, Brown MM, et al. SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp — Georgia, June 2020. MMWR Morb Mortal Wkly Rep. ePub: 31 July 2020. Full-text:

Mid-June 2020. An overnight camp in Georgia (camp A) with trainees, staff members and campers. Wearing cloth masks for campers and opening windows and doors for increased ventilation in buildings were not required. (Cloth masks were required only for staff members.) Camp attendees engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. Of a total of 597 Georgia residents attendending camp A, test results were available for 344 (58%) attendees; among these 260 (76%) were positive. The overall attack rate was 44% (260 of 597), 51% among those aged 6–10 years, 44% among those aged 11–17 years, and 33% among those aged 18–21 years. Attack rates increased with increasing length of time spent at the camp, with staff members having the highest attack rate (56%).



Atyeo C, Fischinger S, Zohar T, et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity 2020, published 30 July. Abstract: Full-text: | See also the graphical abstract:

It still remains unclear why some individuals recover from infection while others rapidly progress and die. In order to investigate whether early SARS-CoV-2-specific humoral immune responses differ across individuals that ultimately recover or die from infection, Galit Alter, Helen Chu and colleagues profiled SARS-CoV-2–specific humoral responses on a small cohort of 22 hospitalized individuals and found that a combination of five SARS-CoV-2-specific antibody measurements were sufficient to distinguish individuals with different disease trajectories, including antibody measurements to S and N. In particular, spike–specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. This immunodominant S-specific antibody profile in convalescents was confirmed in a larger validation cohort. The authors suggest the potential of functional antigen-specific humoral immunity to guide patient care and vaccine development.



Ramlall V, Thangaraj PM, Meydan C et al. Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. Nat Med, published 3 August. Full-text:

Mortality of severe COVID-19 is driven by viral replication and comorbidities that influence immune-mediated pathology. As the complement system is a critical defense against pathogens that, when dysregulated, can contribute to inflammation-mediated pathologies, Sagi Shapira, Nicholas Tatonetti and colleagues explored the role of complement or coagulatory function in SARS-CoV-2 infection and clinical outcome. In a retrospective observational study of 11,116 patients who presented to New York-Presbyterian/Columbia University Irving Medical Center with suspected SARS-CoV-2 infection, they found that history of macular degeneration (a proxy for complement activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for morbidity and mortality in SARS-CoV-2-infected patients. Moreover, patients with AMD succumbed to disease more rapidly than others. The authors also found that transcriptional profiling of nasopharyngeal swabs from 650 control and SARS-CoV-2-infected patients demonstrate that infection results in robust engagement and activation of complement and coagulation pathways.



Lai CKC, Chen Z, Lui G, et al. Prospective study comparing deep-throat saliva with other respiratory tract specimens in the diagnosis of novel coronavirus disease (COVID-19). J Infect Dis 2020, published 1 August. Full-text:

Self-collected specimens for SARS-CoV-2 diagnosis could one day avoid infectious exposure to healthcare workers. Now Paul Chan and colleagues perform a prospective study in two regional hospitals in Hong Kong, examining 563 serial samples collected during the viral shedding period of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. (Instructions for deap throat saliva: first clear your throat by gargling with your own saliva, and then spit out the DTS into a sterile bottle.) Deep throat saliva produced the lowest viral RNA concentration and RT-PCR positive rate compared to conventional respiratory specimens.



Malhotra A, Hepokoski M, McCowen KC, Shyy JYJ. ACE2, Metformin, and COVID-19. iScience 2020, pulished 30 July. Summary: Full-text:

Angiotensin converting enzyme 2 (ACE2) is essential to COVID-19 pathogenesis. Preclinical data suggest that ACE2 may be downregulated after SARS-CoV-2 binding, and treatments which increase ACE2 might prevent cardiopulmonary injury. Now Atul Malhotra, John Shyy and colleagues hypothesize that patients with COVID-19 taking metformin might have higher circulating ACE2 levels, and lower morbidity and mortality. They propose to test this hypothesis through a combination of retrospective cohort studies, and prospective translational studies evaluating the ACE2 axis in COVID-19 patients. The authors also cite an observational study from Wuhan, China, which showed that in-hospital mortality was significantly lower in a metformin group than in a control group (3/104 (2.9%) versus 22/179 (12.3%), p = 0.01; Luo P, Qiu L, Liu Y, et al. Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis. Am J Trop Med Hyg 2020;103(1):69-72. PubMed: Full-text:


Cheng GS, Hill JA. To Toci or Not to Toci for COVID-19: Is That Still the Question? Clin Infect Dis. 2020 Jul 31:ciaa1133. PubMed: Full-text:

Joshua Hill and Guang-Shing Cheng first narrate the story of tocilizumab and the IL-6 receptor in such a way that you understand the impetus to use tocilizumab in hospitalized patients with COVID-19, despite the lack of data from controlled trials. They then go on to comment the study by Somers et al., Tocilizumab for treatment of mechanically ventilated patients with COVID-19, we presented on 12 July ( Excellent summary.


Collateral effects

Mekaoui N, Razine R, Bassat Q, et al. The Effect of COVID-19 on Paediatric Emergencies and Admissions in Morocco: Cannot See the Forest for the Trees? J Trop Pediatr 2020, published 1 August. Full-text:

Where are the sick Moroccan children normally brought to the emergency department? When Nour Mekaoui and colleagues from the Rabat Children’s Hospital, Morocco, compared the number of pediatric consultations (< 16 years) in the emergency department from 16 March to 15 April 2020 with the number of consultations of the same period in the preceding year, they discovered that the number of overall consultations decreased by 74% between the two periods (4232 vs. 1110; p < 0.005). Even the the number of hospitalizations declined (811 in 2019 vs. 471 in 2020, a 41.9% reduction, p < 0.005; see figure). The authors are worried: Where did these severely ill patients go? Might we anticipate a new wave of serious non-COVID-19 pediatric admissions?