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24 October

Epidemiology

Guzzetta G, Riccardo F, Marziano V, Poletti P, Trentini F, Bella A, et al. Impact of a nationwide lockdown on SARS-CoV-2 transmissibility, Italy. Emerg Infect Dis. 2021 Jan. Full-text: https://doi.org/10.3201/eid2701.202114

While preparing for the next lockdown, let’s keep in mind that it worked during the first wave. The national lockdown put in place as of March 11 in Italy brought the net (R_t) reproduction numbers below 1 in most regions and provinces within 2 weeks. Although Rt had been declining steeply even before the national lockdown in regions with intense interventions, Giorgio Guzzetta and colleagues estimate that the epidemic was brought under control only after the implementation of the lockdown. In addition, lockdown was fundamental to prevent an explosion in the number of cases in other regions in which transmission had started weeks later compared with the outbreak epicenters in Lombardy, Veneto and Emilia Romagna.

Virology

Wei J, Alfajaro MM, DeWeirdt PC, et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell October 20, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.10.028

Using genome-wide CRISPR screens in Vero-E6 cells, Jin Wei and colleagues have found some new host genes that affect infection by SARS-CoV-2 and other pandemic coronaviruses. In addition, the authors discovered pro-viral genes and pathways including HMGB1 which seems to have an epigenetic role in regulating ACE2 expression and thus susceptibility (HMGB1 is a pleiotropic protein that binds nucleosomes regulating chromatin in the nucleus and functions as a secreted alarmin in response to virus infection).

McNamara RP, Caro-Vegas C, Landis JT, et al. High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States. Cell Rep October 20, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108352

The D614G mutation now dominates over the initial human strain defined by the SARS-CoV-2/human/CHN/Wuhan-01/2019 isolate. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region, showing that now 57% of strains carry the spike D614G variant, which was associated with higher genome copy numbers. Given the increasing abundance of D614G, further research into its role in pathogenicity and clinical outcomes is warranted.

Du P, Song C, Li R, et al. Specific re-distribution of SARS-CoV-2 variants in the respiratory system and intestinal tract, Clinical Infectious Diseases, ciaa1617. Full-text: https://doi.org/10.1093/cid/ciaa1617

Two distinct variants in a patient: Pengcheng Du and colleagues from Beijing report on a young male patient with mild symptoms who seemingly had a dual-infection of two SARS-CoV-2 variants. Of note, they also observed changes in the distribution of these variants in specimens collected from the respiratory and intestinal tracts during the course of the infection.

Transmission

Poole S, Brendish NJ, Tanner AR, et al. Physical distancing in schools for SARS-CoV-2 and the resurgence of rhinovirus. Lancet Resp Med October 22, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30502-6

Stephen Poole and colleagues from Southampton compared the rate of respiratory virus detection in 2020 with the same period in 2019. Among 3,898 adult patients who were tested between March and September, they observed a drop in the rate of detection of all respiratory viruses including rhinovirus following the nationwide lockdown. Around 2 weeks after the concurrent re-opening of state primary and secondary schools in early September, there was a sharp increase in the number of detections similar to that seen in 2019. Two conclusions: 1. children are a major reservoir for rhinovirus infection, and a key driver of transmission to adults. 2. Current physical distancing measures adopted by schools do not effectively prevent rhinovirus transmission.

Immunology

Baang JH, Smith C, Mirabelli C, et al. Prolonged SARS-CoV-2 replication in an immunocompromised patient. J Infect Dis 2020, jiaa666. Full-text: https://doi.org/10.1093/infdis/jiaa666

Interesting case of “chronic COVID-19” in a patient with mantle cell lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious SARS-CoV-2 virus for at least 119 days. The patient had three admissions related to COVID-19 over a four-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient’s lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. The authors hypothesize that antibody-mediated ablation of B-cell precursors by mosunetuzumab and polatuzumab vedotin was primarily responsible for his prolonged viral shedding.

Vaccines

Mehrotra DV, Janes HE, Fleming TR, et al. Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials. Ann Int Med October 21, 2020. Full-text: https://doi.org/10.7326/M20-6169

Guidance from the FDA recommends minimal phase 3 success criteria for approval of a vaccine: an estimated reduction in the primary endpoint of at least 50% in the vaccine group versus the placebo group, with the 95% CI providing assurance of at least a 30% reduction. The FDA guidance also indicates that acceptable primary endpoints for approval could include SARS-CoV-2 infection, symptomatic infection, severe COVID-19, or some combination of these. Biostatistician Devan V. Mehrotra and colleagues emphasize the need to facilitate harmonized evaluation and comparison of the efficacy of these vaccines. They propose a standard set of clinical endpoints to support pooling data for analyses of immunologic surrogate endpoints.

Severe COVID-19

Botta M, Tsonas AM, Pillay J, et al. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study. Lancet Resp Med October 23, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30459-8

Retrospective observational study at 18 intensive care units in the Netherlands, with a detailed analysis of 553 patients who received mechanical ventilation during the first month of the national outbreak in the country. Median duration of ventilation was long with 13.5 days, placing an enormous burden on ICUs. Lung-protective ventilation with low tidal volume (52%) and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely (from 5 to 20 cm!), despite an invariably low respiratory system compliance. Of note, the PEEP had no impact on outcome. In total, 186/530 (35%) patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation. In total, 21% had thromboembolic complications.

Treatment

Arabi YM, Asiri AY, Assiri AM, et al. Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome. N Engl J Med. 2020 Oct 22;383(17):1645-1656. PubMed: https://pubmed.gov/33026741. Full-text: https://doi.org/10.1056/NEJMoa2015294

In MERS, interferon and lopinavir/r seem to work: This double-blind, placebo-controlled RCT enrolled 95 hospitalized patients at nine sites in Saudi Arabia to receive recombinant interferon beta-1b plus lopinavir/r (intervention) or placebo for 14 days. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Can we learn from this?

Pediatrics

Von Kohorn I, Stein SR, Shikani BT, et al. In utero SARS-CoV-2 Infection. J Pediatric Inf Dis Society, October 22, piaa127. Full-text: https://doi.org/10.1093/jpids/piaa127

This infant most likely acquired SARS-CoV-2 hematogenously from mother at or prior to delivery. All caregivers were aware of the mother’s COVID-19 diagnosis prior to delivery. According to the authors, it is extremely unlikely that the infant could have acquired infection from the mother via the respiratory route with the brief and distant exposure in the delivery room. However, SARS-CoV-2 RNA was not found in placental tissue.

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