Copy-editor: Rob Camp
Epidemiology
Denny TN, Andrews L, Bonsignori M, et al. Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus — Duke University, Durham, North Carolina, August 2–October 11, 2020. MMWR Morb Mortal Wkly Rep. ePub: 17 November 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6946e1
Test them all? In fall 2020, Duke University’s COVID-19 prevention strategy included risk reduction behaviors, but also frequent testing using pooled SARS-CoV-2 PCR testing, and contact tracing. Of 10,265 students who received testing 68,913 times, 84 had positive results. Of these, 51% were asymptomatic, and some had high viral loads. This plan allowed campus to remain open for 10 weeks of classes without substantial outbreaks among residential or off-campus populations. Importantly, no evidence from contact tracing linked transmission with in-person classes. Pooled testing permitted a nearly 80% savings in use of reagents and laboratory resources compared with testing each individual specimen.
Immunology
Samuel RM, Majd H, Richter MN, et al. Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men. Cell Stem Rep November 17, 2020. Full-text: https://doi.org/10.1016/j.stem.2020.11.009
Finasteride for COVID-19? Ryan M. Samuel and colleagues from San Francisco identified a link between male sex hormone signaling and regulation of the SARS-CoV-2 receptor ACE2 and co-receptor TMPRSS2, possibly explaining the higher complication rates in men. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. Of note, treatment with anti-androgenic drugs such as finasteride reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection. Finally, clinical data on COVID-19 patients demonstrated that prostate diseases, which are linked to elevated androgen, are significant risk factors and genetic variants that increase androgen levels are associated with higher disease severity.
Li A, Ling Y, Song Z, et al. Early plasma IL-37 responses accompanied with low inflammatory cytokines correlate with benign clinical outcomes during SARS-CoV-2 infection. J Infect Dis. 2020 Nov 17:jiaa713. PubMed: https://pubmed.gov/33197260. Full-text: https://doi.org/10.1093/infdis/jiaa713
Ang Li and colleagues from Shanghai examined early responses of IL-37, a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients prior to any clinical intervention and determined its correlation with clinical prognosis. Higher early IL-37 responses correlated with earlier viral RNA negative conversion, chest CT image improvement and cough relief, consequently resulting in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower IL-6 and IL-8 and higher IFN-α, and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and CRP. Moreover, IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in hACE2-transgenic mice infected with SARS-CoV-2.
Woldemeskel BA, Kwaa AK, Garliss CC, Laeyendecker O, Ray SC, Blankson JN. Healthy donor T cell responses to common cold coronaviruses and SARS-CoV-2. J Clin Invest. 2020 Nov 16:143120. PubMed: https://pubmed.gov/32966269. Full-text: https://doi.org/10.1172/JCI143120
Bezawit A. Woldemeskel and colleagues from Baltimore used the ELISPOT assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses and SARS-CoV-2 in 21 healthy donors seronegative for SARS-CoV-2. An in vitro expansion culture assay was also used to analyze memory T cell responses. Responses to the spike protein of the 3 common cold coronaviruses were found in many of the donors. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses.
Vaccine
Zhang Y, Zeng G, Pan H. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet November 17, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30843-4
Phase I/II study of an inactivated vaccine candidate against COVID-19. In total, 743 participants at the Suining County of Jiangsu province, China, received at least one dose (n = 143 for Phase 1 and n = 600 for Phase 2; safety population). At day 28 after the days 0 and 28 vaccination schedule, seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group which is the suggested dose for efficacy assessment in future Phase III trials. Adverse events such as mild injection-site pain, occurred in 81 (17%) of 480 vaccine recipients.
Bar-Zeev N, Kochhar S. Expecting the unexpected with COVID-19 vaccines. Lancet November 17, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30870-7
According to this detailed comment, like all Phase II trials, the results must be interpreted with caution until Phase III results are published. Neutralising titers were substantially lower than those seen in 117 convalescent patients who previously had COVID-19 tested in the same laboratory. A demonstration of longevity of response and of empiric protection from this vaccine candidate will be important.
Clinical
Bois MC, Boire NA, Layman AJ, et al. COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. Circulation. 2020 Nov 16. PubMed: https://pubmed.gov/33197204. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050754
What are the underlying mechanisms of cardiac complications? This small, but detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series of 15 COVID-19 cases showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently had cardiac fibrin microthrombi (12/16), without universal acute ischemic injury. Moreover, myocarditis was present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Vaira LA, Hopkins C, Sandison A, et al. Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia. J Laryngol Otol. 2020 Nov 16:1-13. PubMed: https://pubmed.gov/33190655. Full-text: https://doi.org/10.1017/S0022215120002455
Interesting case report of a patient who presented with anosmia persisting for more than three months after infection. MRI did not reveal any pathological findings: the olfactory bulb and clefts were of normal volume, without signal anomalies. However, the biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.
Alvarez-Garcia J, Lee S, Gupta A, et al. Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2020 Nov 17;76(20):2334-2348. PubMed: https://pubmed.gov/33129663. Full-text: https://doi.org/10.1016/j.jacc.2020.09.549
Retrospective analysis of 6439 patients admitted for COVID-19 at 5 hospitals in New York City between February 27 and June 26, 2020. Compared with patients without heart failure (HF), those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%), and mortality (40.0% vs. 24.9%). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.
Collateral damage
De Luca G, Verdoia M, Cercek M, et al. Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI. J Am Coll Cardiol. 2020 Nov 17;76(20):2321-2330. PubMed: https://pubmed.gov/33183506. Full-text: https://doi.org/10.1016/j.jacc.2020.09.546
A total of 6609 patients underwent primary percutaneous coronary intervention (PPCI) in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.81; 95% confidence interval: 0.78 to 0.84). Furthermore, the pandemic was associated with a significant increase in “door-to-balloon” and total ischemia times, which may have contributed to higher mortality during the pandemic.
Co-morbidities
Shah GL, DeWolf S, Lee YJ, et al. Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. J Clin Invest. 2020 Nov 16:141777. PubMed: https://pubmed.gov/32897885. Full-text: https://doi.org/10.1172/JCI141777
Gunjan L. Shah from Memorial Sloan Kettering Cancer Center and colleagues retrospectively investigated 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days). Overall survival at 30 days was 78%. Mortality was largely driven by patients with active malignancy, especially relapsed leukemia, in whom the goals of care were affected both by COVID-19 severity and the decision to forgo anti-cancer treatment during an active infection. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Many patients were able to recover from COVID-19 infection and mount an antibody response with similar overall survival to the general hospitalized population.
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