+++ Severe COVID-19 +++

* * * Next update: 24 November. In the meantime, find the global updates at 7 Days. * * *

14 November

Zietz M, Zucker J, Tatonetti NP. Associations between blood type and COVID-19 infection, intubation, and death. Nat Commun 11, 5761 (2020). Full-text: https://doi.org/10.1038/s41467-020-19623-x

This next study is about the association between ABO and Rh blood types and infection, intubation, and death. Here, the authors used observational healthcare data on 14,112 individuals tested for SARS-CoV-2 with known blood type in the New York Presbyterian hospital system. Risk of intubation was decreased among A and increased among AB and B types, compared with type O, while risk of death was increased for type AB and decreased for types A and B. Rh-negative blood type might have a protective effect for all three outcomes.


Gude F, Riveiro V, Rodríguez-Núñez N, et al. Development and validation of a clinical score to estimate progression to severe or critical state in COVID-19 pneumonia hospitalized patients. Sci Rep 10, 19794 (2020). Full-text: https://doi.org/10.1038/s41598-020-75651-z

Five predictors determined within 24 h of hospital admission may identify patients at risk for COVID-19 disease progression: diabetes, higher age, a low lymphocyte count, decreasing SaO2, and any pH alteration. This is the outcome of a study by Lucía Ferreiro, Francisco Gude and colleagues who analyzed 229 patients who were admitted for pneumonia. The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤ 5%, 6–25%, and > 25% exhibited disease progression, respectively.


12 November

Ledford H. Why do COVID death rates seem to be falling? Nature 2020, published 11 November. Full-text: https://www.nature.com/articles/d41586-020-03132-4

Hard-won experience, changing demographics and reduced strain on hospitals are all possibilities — but no one knows how long this change will last. By Heidi Ledford.


11 November

Wang F, Huang S, Gao R. Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility. Cell Discov 6, 83 (2020). Full-text: https://doi.org/10.1038/s41421-020-00231-4

HLA-A*11:01, B*51:01, and C*14:02 alleles might predispose to severe COVID-19. This is the result of a host genetic study deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity. Lei Liu, Fang Wang and colleagues conducted single-variant and gene-based association tests among five severity groups: asymptomatic, mild, moderate, severe, and critically ill patients. Find out more about genes involved in the interleukin-1 (IL-1) signaling pathway and the stability of the TMPRSS2 protein.


9 November

Liu Y, Lv J, Liu J. et al. Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19. Cell Res November 6, 2020. Full-text: https://doi.org/10.1038/s41422-020-00435-z

It’s mucus: this great work may potentially explain the silent hypoxia that has emerged as a unique feature of COVID-19. Yuying Liu and colleagues from Beijing/China show that mucins are accumulated in the bronchoalveolar lavage fluid and are upregulated in the lungs of severe SARS-CoV-2-infected mice and macaques. They also found that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity.

4 November

Evans RM, Lippman SM. Shining Light on the COVID-19 Pandemic: A Vitamin D Receptor Checkpoint in Defense of Unregulated Wound Healing. Cell Metab. 2020 Sep 11;32(5):704-9. PubMed: https://pubmed.gov/32941797. Full-text: https://doi.org/10.1016/j.cmet.2020.09.007

Ronald Evans and Scott Lippman propose repurposing paricalcitol (vitamin D analog) infusion therapy to restrain the COVID-19 cytokine storm, reasoning that vitamin D deficiency and the failure to activate the vitamin D receptor can aggravate this respiratory syndrome by igniting a wounding response in stellate cells of the lung. Find out what could be the appropriate dose and the potential complications.


31 October

Mastrangelo A, Germinarkio BN, Ferrante M, et al. Candidemia in COVID-19 patients: incidence and characteristics in a prospective cohort compared to historical non-COVID-19 controls. Clinical Infectious Diseases, 30 October 2020, ciaa1594. Full-text: https://doi.org/10.1093/cid/ciaa1594

This study found an increased incidence of candidemia in hospitalized patients with COVID-19 compared to a historical non-COVID-19 cohort (11 vs. 1.5 cases per 10.000-PDFU). The authors found no imbalance in several predisposing risk factors for candidemia, with the notable exception of a higher proportion of subjects in ICU and on immunosuppressive agents in the COVID-19 cohort.


30 October

Mueller AA, Tamura T, Crowley CP, et al. Inflammatory biomarker trends predict respiratory decline in COVID-19 patients. Cell Rep Med 2020, published 28 October. Full-text: https://doi.org/10.1016/j.xcrm.2020.100144

Increasing C-reactive protein (CRP) values during the first 48 hours of hospitalization is a better predictor of respiratory decline than initial CRP levels. A rapid rise in CRP levels precedes respiratory deterioration and intubation, while CRP levels plateau in patients that remain stable. A finding of a single-center retrospective cohort analysis of 100 hospitalized COVID-19 patients.


29 October

Beck DB, Aksentijevich I. Susceptibility to severe COVID-19. Science. 2020 Oct 23;370(6515):404-405. PubMed: https://pubmed.gov/33093097. Full-text: https://doi.org/10.1126/science.abe7591

Identifying the determinants of the clinical spectrum, from people with asymptomatic disease to patients with severe COVID-19 is one of the pressing questions surrounding SARS-CoV-2. The spectrum varies from asymptomatic SARS-CoV-2 infection (up to 40%) to severe COVID-19 (fatality near 1%). David Beck and Ivona Aksentijevich discuss two analyses of >1600 patients infected with SARS-CoV-2 from >15 countries to identify endogenous factors that determine susceptibility to severe COVID-19. We presented the papers on September 25:

Bastard P, Rosen LB, Zhang Q, et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020, published 24 September. Full-text: https://science.sciencemag.org/content/early/2020/09/23/science.abd4585

Zhang Q, Bastard P, Liu Z, et al: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020, published 24 September. Full-text: https://science.sciencemag.org/content/early/2020/09/23/science.abd4570


24 October

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.


22 October

Cates J, Lucero-Obusan C, Dahl RM, et al. Risk for In-Hospital Complications Associated with COVID-19 and Influenza — Veterans Health Administration, United States, October 1, 2018–May 31, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1528–1534. Full-text: http://dx.doi.org/10.15585/mmwr.mm6942e3

COVID-19 is deadlier than influenza. Now, Jordan Cates and colleagues have quantified the difference: hospitalized patients with COVID-19 had a more than five times higher risk for in-hospital death and increased risk for 17 respiratory and nonrespiratory complications than did hospitalized patients with influenza. The risks for sepsis and respiratory, neurologic, and renal complications of COVID-19 were higher among non-Hispanic Black or African American and Hispanic patients than among non-Hispanic White patients.


20 October

Leiter RE. Reentry. N Engl J Med. 2020 Oct 14. PubMed: https://pubmed.gov/33053276. Full-text: https://doi.org/10.1056/NEJMp2027447

“While we try to heal from the collective trauma we experienced in our hospital over the worst 4 months of the local epidemic, I struggle to know where to look. Peering into the future, given what we see on the news, saturates me with dread. And yet it’s too early to look back. Perspective can’t develop in the presence of open wounds.”


19 October

Rodrigues JY, Le Pape P, Lopez O, et al. Candida auris: a latent threat to critically ill patients with COVID-19, Clinical Infectious Diseases. Full-text: https://doi.org/10.1093/cid/ciaa1595

Jose Y Rodriguez and colleagues report on 20 cases of fungemia in hospitalized patients with SARS-CoV-2 infection in 4 institutions in the northern region of Colombia from June to September 2020. Nineteen of the 20 patients had received steroids and 15/19 were had nonalbicans Candida fungemia.


18 October

Thomas R, Lotfi T, Morgano GP, et al. Update Alert 2: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19. Annals Int Med 13 October 2020. Full-text: https://doi.org/10.7326/L20-1211

Updated of a living systematic review on ventilation techniques, analyzing all new studies published until end of July. Bottom line: Nothing new. Noninvasive ventilation may have similar effects to IMV on mortality, but the evidence is uncertain.


13 October

de Nooijer AH, Grondman I, Janssen NAF, et al. Complement activation in the disease course of COVID-19 and its effects on clinical outcomes. J Infect Dis 2020, published 10 October. Full-text: https://doi.org/10.1093/infdis/jiaa646

In this prospective, longitudinal, single center study, Leo Joosten, Aline de Nooijer and colleagues analyzed plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) for 197 patients with confirmed COVID-19. Complement factors C3a, C3c and TCC were significantly increased in plasma of COVID-19 patients compared to healthy controls (p<0.05). These complement factors were especially elevated in ICU patients during the entire disease course (p<0.005 for C3a and TCC).


11 October

Overmyer KA, Shishkova E, Miller IJ, et al. Large-scale Multi-omic Analysis of COVID-19 Severity. Cell Systems 2020, published 7 October. Full-text: https://doi.org/10.1016/j.cels.2020.10.003

In this cohort study involving 128 patients with and without COVID-19 diagnosis, Ariel Jaitovich, Katherine Overmyer and colleagues monitored thousands of biomolecules in relation to the COVID-19 disease severity and outcomes. They mapped more than 200 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. The authors make their data available through a free web resource – https://covid-omics.app, calling for experts worldwide to mine these








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