Publications

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC) of 4.0 nM (180 ng ml). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.

Palliative care teams and intensive care teams have experience providing goals-of-care guidance for critically ill patients and families. Critical coronavirus disease 2019 (COVID-19) infection is defined as infection requiring intensive care unit care, respiratory support, and often multiorgan involvement. This case presents a 53-year-old critically ill COVID-19 patient in multisystem organ failure who appeared hours from death despite best medical efforts. Comfort-focused care and compassionate extubation were offered after all medical teams felt near certain that death was imminent. Overnight, while options were being considered by the family, the patient began to markedly improve hemodynamically and was extubated several days later. Weeks later, the patient survived the hospital stay and was discharged to rehabilitation. After rehabilitation he returned home, able to walk, communicate freely, and independently perform all activities of daily living. Dialysis was no longer necessary and was stopped. The challenges of assisting in goals-of-care conversations for patients with serious COVID-19 infection are discussed.