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By Christian Hoffmann &
Bernd S. Kamps
16 June
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Epidemiology
Stoke EK, Zambrano LD, Anderson KN. Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020. MMWR June 15, 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6924e2.htm
A detailed picture of the epidemic in the US. This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22–May 30, 2020. Some key messages: Overall, 14% of patients were hospitalized, 2% were admitted to an intensive care unit (ICU), and 5% died. Among cases with known race and ethnicity, 33% of persons were Hispanic, 22% were black, and 1.3% were non-Hispanic American Indian or Alaska Native. These findings suggest that persons in these groups, who account for 18%, 13%, and 0.7% of the U.S. population, respectively, are disproportionately affected by the COVID-19 pandemic.
Thornton J. Covid-19: Africa’s case numbers are rising rapidly, WHO warns. BMJ 2020; 369. Full-text: https://doi.org/10.1136/bmj.m2394
A brief but concerning review on the situation in Africa. Since the virus was first detected in Egypt on 14 February, it took 98 days to reach 100,000 cases and only 18 days to move to 200,000 cases on the continent. More than 5,600 people have died from the illness, 70% of whom were in just five countries: Algeria, Egypt, Nigeria, South Africa, and Sudan.
Transmission
Cox RJ, Brokstadt KA, Krammer F, et al. Seroconversion in household members of COVID-19 outpatients. Lancet June 15, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30466-7
This study from Norway shows that detection of seroconversion might provide a more accurate picture of attack rates in households than intermittent RT-PCR testing. Of 158 cases, 125 (79%) tested positive for antibodies and 12 (8%) were defined as borderline. In 77 household members, 24 (31%) tested positive and two (3%) were borderline.
Comorbidities
Furfaro F, Vuitton L, Fiorino G, et al. SFED recommendations for IBD endoscopy during COVID-19 pandemic: Italian and French experience. Nat Rev Gastroenterol Hepatol. 2020 Jun 11:1-10. PubMed: https://pubmed.gov/32528139 . Full-text: https://doi.org/10.1038/s41575-020-0319-3
This perspective aims to provide a guide based on the Italian and French experience to better face the difficulties encountered by endoscopists during this pandemic. Some helpful recommendations regarding the use of personal protective equipment (both for patients and HCW) are proposed and different scenarios in endoscopic IBD management are evaluated to suggest when endoscopy could be rescheduled and replaced by alternative biomarkers.
Treatment
Marovich M, Mascola JR, Cohen MS. Monoclonal Antibodies for Prevention and Treatment of COVID-19. JAMA June 15, 2020. Full-text: https://doi.org/10.1001/jama.2020.10245
Neutralizing monoclonal antibodies to SARS-CoV-2 have the potential for both therapeutic and prophylactic applications (probably more than all antiviral drugs that are currently being tested). This viewpoint summarizes current knowledge. Several mAbs are poised to enter clinical trials during the summer of 2020. Trials will include treatment of patients with SARS-CoV-2 infection, with varying degrees of illness, to block disease progression. Given the long half-life of most mABs (approximately 3 weeks for IgG1), a single infusion should be sufficient.
Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 15 Jun 2020: eabd0831. Full-text: https://doi.org/10.1126/science.abd0831
Elegant cell experiments, showing that a combination of antibodies may provide a powerful way to minimize mutational escape by SARS-CoV-2; in particular, two antibodies were chosen so as to bind to distinct and non-overlapping regions of the viral target (in this case, the RBD of the spike protein), in order to thus require the unlikely occurrence of simultaneous mutations at two distinct genetic sites for viral escape.
Rogers TF, Zhao F, Huang D, et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 15 Jun 2020: eabc7520. Full-text: https://doi.org/10.1126/science.abc7520
Using a high-throughput rapid system for antibody discovery, the authors isolated more than 1000 mAbs from 3 convalescent donors by memory B cell selection using SARS-CoV-2 S or RBD (receptor-binding domain) recombinant proteins. Of note, only a small fraction of these Abs was neutralizing, highlighting the value of deep mining of responses to access the most potent Abs. RBD-nAbs that directly compete with ACE2 are clearly the most preferred for prophylactic and therapeutic applications, and as reagents to define nAb epitopes for vaccine. With these nABs, Syrian hamsters were protected from weight loss. However, animals that received higher doses also showed body weight loss, possibly indicating antibody-mediated enhanced disease.
Brouwer PJ, Caniels TG, van der Straten K, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 15 Jun 2020: eabc5902. Full-text: https://doi.org/10.1126/science.abc5902
Antibodies from convalescent COVID-19 patients had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection as low as 0.007 μg/mL. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites. The authors isolated 19 neutralizing antibodies that target a diverse range of antigenic sites on the S protein, of which two showed picomolar (very strong!) neutralizing activities.
Tedder RS, Semple MG. Appropriate selection of convalescent plasma donors for COVID-19. Lancet Inf Dis June 15, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30470-9
The authors report on unpublished data (their own), indicating that quantification of specific antibody to the receptor-binding domain (RBD) will indicate levels of neutralising antibodies. This may help to find the best plasma donors. So why don’t they publish their data?
Pediatrics
Stewart DJ, Hartley JC, Johnson M, et al. Renal dysfunction in hospitalised children with COVID-19. Lancet Child Adol Health. June 15, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30178-4
Of 52 hospitalized children, 24 (46%) had elevated serum creatinine, and 15 (29%) met the diagnostic criteria for acute kidney injury (AKI). Most AKI cases occurred in those admitted to the pediatric ICU (93%), and in those with pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS; 73%). This underlines the importance of renal function surveillance in all hospitalised pediatric cases of COVID-19, while simultaneously avoiding factors that exacerbate kidney injury, such as hypovolemia and the use of nephrotoxic drugs. According to the authors, standard care should involve screening for nephritis and follow-up for long-term sequelae of acute kidney injury, such as hypertension and proteinuria.