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By Christian Hoffmann &
Bernd S. Kamps

28 May

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Summary

First, reduce transmission of SARS-CoV-2 as there is growing evidence that infectious aerosol particles can be released during breathing and speaking by asymptomatic infected individuals; look into super-spreading events (SSEs) in Tianjin, China, and determine the reproductive number R and the dispersion parameter k; and investigate the emergence of super-spreading events (SSEs) in Guangzhou and explore the secondary attack rate from different types of contact with 38 pre-symptomatic patients.

Afterward, counsel patients about the riskes of continuing to work in the midst of the pandemic; screen and test patients admitted for childbirth; and study emergency guidelines for radiation therapy of hematological malignancies.

Compare remdesivir 5 vs 10 days in a trial that lacked a placebo control; discuss with your colleagues five Waldenstroem macroglobulinemia patients on Bruton tyrosine kinase (BTK) inhibitor ibrutinib; and use specific human monoclonal antibody (MAbs) from a convalescent COVID-19 patient and demonstrate neutralization activity in 6 rhesus monkeys in both prophylactic and treatment settings.

 

Epidemiology

Larochelle MR. “Is It Safe for Me to Go to Work?” Risk Stratification for Workers during the Covid-19 Pandemic. N Engl J Med. 2020 May 26. PubMed: https://pubmed.gov/32453518 . Full-text: https://doi.org/10.1056/NEJMp2013413

A simple framework to help clinicians counsel patients about continuing to work in the midst of the pandemic based on their occupational risk of contracting SARS-CoV-2 and their risk of death if they are infected.

 

Campbell KH, Tornatore JM, Lawrence KE, et al. Prevalence of SARS-CoV-2 Among Patients Admitted for Childbirth in Southern Connecticut. JAMA. 2020 May 26. PubMed: https://pubmed.gov/32453390 . Full-text: https://doi.org/10.1001/jama.2020.8904

From April 2, 2020, to April 29, 2020, screening and testing of patients admitted for childbirth was initiated at 3 Yale New Haven Health hospitals in southern Connecticut. Of 770 patients, 30 (3.9%) tested positive for SARS-CoV-2, of whom 22 (73%) were asymptomatic.

 

Transmission

Prather KA, Wang CC, Schooley RT. Reducing transmission of SARS-CoV-2. Science  27 May 2020: eabc6197, https://doi.org/10.1126/science.abc6197

This perspective clearly shows that masks and testing are necessary and essential to combat asymptomatic spread in aerosols and droplets. It cannot be repeated often enough: infectious aerosol particles can be released during breathing and speaking by asymptomatic infected individuals. No masking maximizes exposure, whereas universal masking results in the least exposure.

 

Zhang Y, Li Y, Wang L, Li M, Zhou X. Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China. Int J Environ Res Public Health. 2020 May 24;17(10):E3705. PubMed: https://pubmed.gov/32456346 . Full-text: https://doi.org/10.3390/ijerph17103705

Over the last few weeks, it has become very clear that some individuals spread to a disproportionate number of individuals, compared to most individuals who infect a few or no-one. This important paper looked at transmission heterogeneity and the emergence of these super-spreading events (SSEs). In total, 135 cases from official public sources in Tianjin, China were grouped into 43 transmission chains. The reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) were estimated to be 0.67 (95% CI: 0.54-0.84) and 0.25 (95% CI: 0.13-0.88), respectively. Transmission was very heterogeneous and one SSE was identified. Transmission characteristics of COVID-19 need more exploration and investigation on a large scale.

 

Zhang W, Cheng W, Luo L, et al. Secondary Transmission of Coronavirus Disease from Presymptomatic Persons, China. Emerg Infect Dis. 2020 May 26;26(8). PubMed: https://pubmed.gov/32453686 . Full-text: https://doi.org/10.3201/eid2608.201142

Contact-tracing surveillance data collected in Guangzhou, China during January 28 – March 15, 2020, to explore the secondary attack rate from different types of contact with 38 pre-symptomatic patients. The secondary attack rates (SAR) among household contacts was 16.1% and was 1.1% for social contacts, and 0 for workplace contacts. Older close contacts had the highest SAR compared to other age groups.

 

Comorbidities

Yahalom J, Dabaja BS, Ricardi U. ILROG emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic. Blood 2020, 135 (21): 1829–1832. https://doi.org/10.1182/blood.2020006028

Realizing the need to reduce the exposure of patients and staff to potential infection with COVID-19, a task force makes recommendations for alternative radiation treatment schemes. The emphasis is on maintaining clinical efficacy and safety by increasing the dose per fraction while reducing the number of daily treatments.

 

Treatment

Goldman JD, Lye DC, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. May 27, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2015301?query=featured_home

In this randomized, open-label, Phase III trial in 397 hospitalized patients with severe COVID-19 and not requiring IMV, clinical improvement at day 14 was 64% with 5 days remdesivir and 54% with 10 days. After adjustment for (significant) baseline imbalances in disease severity, outcomes were similar. The most common adverse events were nausea (9%), worsening respiratory failure (8%), elevated ALT level (7%), and constipation (7%). Because the trial lacked a placebo control, it was not a test of efficacy for remdesivir.

 

Shi R, Shan C, Duan X, et al. A human neutralizing antibody targets the receptor binding site of SARS-CoV-2. Nature. 2020 May 26. PubMed: https://pubmed.gov/32454512 . Full-text: https://doi.org/10.1038/s41586-020-2381-y

Another interesting specific human monoclonal antibody (MAb) from a convalescent patient. CB6 demonstrated potent neutralization activity in vitro against SARS-CoV-2 and worked in 6 rhesus monkeys at both prophylactic and treatment settings. This MAb recognizes an epitope that overlaps with ACE2 binding sites in SARS-CoV-2 receptor binding domain (RBD), thereby interfering with the virus/receptor interactions by both steric hindrance and direct interface-residue competition.

 

Treon SP, Castillo JJ, Skarbnik AP, et al. The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19–infected patients. Blood 2020, 135: 1912–1915. https://doi.org/10.1182/blood.2020006288

Five Waldenstroem macroglobulinemia patients on Bruton tyrosine kinase (BTK) inhibitor ibrutinib, 420 mg/d, did not require hospitalization. Their course was marked by steady improvement, and resolution or near resolution of COVID-19 symptoms during the follow-up period. Clinical trials examining the benefit of BTK inhibitors to abrogate lung injury are being initiated.