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By Christian Hoffmann &
Bernd S. Kamps

8 June

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Epidemiology

Xu X, Sun J, Nie S, et al. Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nat Med. 2020 Jun 5. PubMed: https://pubmed.gov/32504052 . Full-text: https://doi.org/10.1038/s41591-020-0949-6

To estimate the cumulative prevalence, authors evaluated IgM and IgG antibodies in 17,368 individuals from Wuhan, China. The seropositivity in Wuhan was low, varying between 3.2% and 3.8% in different sub-cohorts. As seen in other studies, an early and a higher level of IgG response was observed, compared to IgM.

 

Graham N, Junghans C, Downes R, et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes. J Infect. 2020 Jun 3:S0163-4453(20)30348-0. PubMed: https://pubmed.gov/32504743 . Full-text: https://doi.org/10.1016/j.jinf.2020.05.073

Outbreak investigation involving 394 residents and 70 staff in 4 nursing homes in central London. Overall, 26% of residents died over a two-month period. Systematic testing identified 40% of residents as positive for SARS-CoV-2 and of these, 43% were asymptomatic and 18% had only atypical symptoms during the two weeks prior to testing. Of note, this was also true of many residents in the days leading up to death indicating that even in severe COVID-19, fever and cough were commonly absent. 4% of asymptomatic staff also tested positive.

 

Immunology

Subbarao K, Mahanty S. Respiratory Virus Infections: Understanding COVID-19. Immunity. 2020 May 20:S1074-7613(20)30212-0. PubMed: https://pubmed.gov/32497522 . Full-text: https://doi.org/10.1016/j.immuni.2020.05.004

Nice review about the immune response to respiratory viruses. What happens when the virus reaches the respiratory mucosa? What are the consequences of infection in the host?

 

Virology, Vaccine

Wang H, Zhang Y, Huang B, et al. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell 2020, June 06. Full-text: https://doi.org/10.1016/j.cell.2020.06.008

Will this be the first vaccine? Compared with the adenovirus-vectored and the DNA vaccine, inactivated vaccine development and production is a conventional and mature technology (main pro: large amounts of vaccine doses can be easily manufactured, main con: safety issues, including an antibody-dependent worsening of the infection). BBIBP-CorV, an inactivated SARS-CoV-2 vaccine, induced high levels of neutralizing antibody in several animal models, including 8 rhesus macaques,  protecting them against SARS-CoV-2 infection. There was no observable antibody-dependent infection enhancement or immunopathological exacerbation. A Phase I clinical trial of BBIBP-CorV is currently in progress and a Phase II clinical trial has recently been initiated.

 

Transmission

Newman A, Smith D, Ghai RR. First Reported Cases of SARS-CoV-2 Infection in Companion Animals — New York, March–April 2020. MMWR, June 8, 2020, 69. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6923e3.htm

American cats are not protected: Two domestic cats with respiratory illnesses lasting 8 and 10 days were the first reported companion animals with SARS-CoV-2 infection in the United States. Both cats were owned by persons with suspected or confirmed COVID-19. According to the authors, persons with COVID-19 should avoid contact with animals. Companion animals that test positive for SARS-CoV-2 should be monitored and separated from persons and other animals until they recover. Good news: both cats fully recovered.

 

Diagnostics

Cheng MP, Yansouni CP, Basta NE, et al. Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2. Annals Int Med 2020, Jun 4. Full-text: https://doi.org/10.7326/M20-2854

For SARS-CoV-2, the accuracy of antibody test results and the appropriate test interpretation both depend on clinical context. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. This review also includes a decision tree for interpreting antibody test results.

 

Long DR, Gombar S, Hogan CA. Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients. Clinical Infectious Diseases 2020, June 7. Full-text:  https://doi.org/10.1093/cid/ciaa722

If the first PCR is negative, a second PCR only yields a small number of positive results. Using data for 20,912 patients, authors analyzed the frequency of SARS-CoV-2 RT-PCR test discordance among individuals initially testing negative by nasopharyngeal swab who were retested on clinical grounds within 7 days. The frequency of subsequent positivity within this window was only 3.5% and similar across institutions.

 

Treatment

Roschewski M, Lionakis MS, Sharman JP, et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19.  Science Immunology  05 Jun 2020: Vol. 5, Issue 48, eabd0110. Full-text: https://doi.org/10.1126/sciimmunol.abd0110

Ex vivo analysis revealed significantly elevated bruton tyrosine kinase (BTK, regulates macrophage signalling and activation) activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. In a pilot study, 19 patients with severe COVID-19 received the BTK inhibitor acalabrutinib. Within 10-14 days, oxygenation improved “in a majority of patients”, often within 1-3 days, and inflammation markers and lymphopenia normalized quickly in most patients. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy. A confirmatory RCT is underway.

 

Pediatrics

Whittaker E, Bamford A, Kenny J, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. Published online June 8, 2020. Full-text: https://doi.org/10.1001/jama.2020.10369

This case series included 58 hospitalized children, meeting definitional criteria for (attention, a novel term/syndrome) “PIMS-TS”, including fever, inflammation, and organ dysfunction. Of these children, all had fever and nonspecific symptoms, such as abdominal pain (53%), rash (52%), and conjunctival injection (45%); 50% developed shock and required inotropic support or fluid resuscitation; 22% met diagnostic criteria for Kawasaki disease; and 14% had coronary artery dilatation or aneurysms. Some clinical and laboratory characteristics had important differences compared with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome.

 

McCrindle BW, Manlhiot C. SARS-CoV-2–Related Inflammatory Multisystem Syndrome in Children Different or Shared Etiology and Pathophysiology as Kawasaki Disease? JAMA June 8, 2020. Full-text: https://doi.org/10.1001/jama.2020.10370

Nice editorial on current knowledge (and knowledge gaps) on PIMS-TS and Kawasaki Disease (KD), noting that the differences between PIMS-TS and Kawasaki Disease (KD) are just as interesting as the similarities. For PIMS-TS, SARS-CoV-2 may be acting either as the trigger or an immune-modulating factor.