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March 13, 2020

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response

Author Affiliations
  • 1Department of Pathophysiology and Transplantation, University of Milan, Italy
  • 2Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 3Dipartimento Anestesia e Terapie Intensive, Humanitas Rozzano, Milan, Italy
JAMA. 2020;323(16):1545-1546. doi:10.1001/jama.2020.4031

On February 20, 2020, a patient in his 30s admitted to the intensive care unit (ICU) in Codogno Hospital (Lodi, Lombardy, Italy) tested positive for a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). He had a history of atypical pneumonia that was not responding to treatment, but he was not considered at risk for COVID-19 infection.1 The positive result was immediately reported to the Lombardy health care system and governmental offices. During the next 24 hours, the number of reported positive cases increased to 36. This situation was considered a serious development for several reasons: the patient (“patient 1”) was healthy and young; in less than 24 hours, 36 additional cases were identified, without links to patient 1 or previously identified positive cases already in the country; it was not possible to identify with certainty the source of transmission to patient 1 at the time; and, because patient 1 was in the ICU and there were already 36 cases by day 2, chances were that a cluster of unknown magnitude was present and additional spread was likely.

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    6 Comments for this article
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    Emergency Response of a Western Country to the COVID-19 "Tsunami"
    Giuliano Ramadori, Professor of Medicine | University Clinic,Internal Medicine,Göttingen,Germany
    This is an impressive report about the challenge the Lombardy Health care system had to face after the outbreak of COVID-19 became clear in an area of Italy with a large Chinese minority. In fact it was supposed that the virus originated from China but the first patient with COVID-19 pneumonia is a young marathon runner of 38 year of age and not a person belonging to the Chinese minority. It is still unclear how he, his wife and his parents became infected.

    The number of ICU-patients is impressive. Even more impressive is the velocity of the increase of
    the number of people who needed ICU care.

    It would be more impressive for the countries who are reluctant to consider preventive measures be taken to have the number of patients reported who unfortunately died while being treated at the ICU. How many patients were Chinese?

    The relatively  high number of the ICU admissions in the Lombardy compared to the numbers observed in China may be primarily due to the number of ICU-beds available.

    I am surprised to read the word "race" as one of the possible predisposing factors for ICU-admission. Ligi Luca Cavalli Sforza, who died in Belluno in August 2018 was the italian "grandfather of the field of human population genetics"(1) who clearly demonstrated that humans belong to one single race.Therefore "race" can not be a predisposing factor for ICU-admission in Lombardy besides age and comorbidities.

    REFERENCE

    1. Henn BM,Quintana-Murci L.:Editorial Overview:The history, geography and adaptation of human genes: A tribute to L.Luca Cavalli-Sforza.Curr Opin Genetics & Developement 2018;53:iii-v
    CONFLICT OF INTEREST: None Reported
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    Mild COVID-19 Cases: Who Might Be Hospitalized And Who Can Be Quarantined?
    Arturo Tozzi, Pediatrician | University of North Texas
    The escalating number of Italian patients with positive COVID-19 test results causes an unmanageable increase of hospital admissions, including of mild/moderate cases. Indeed, about three fifths of the patients with confirmed SARS-CoV-2 are currently hospitalized in Italy, while the rest are home quarantined. Therefore, it would be useful to grasp who of the patients affected by mild to moderate symptoms require hospital admission instead of household follow-up.

    White blood cell counts in SARS-CoV-2-positive but not critically ill patients might be a way to determine who requires hospitalization. Indeed, lower lymphocyte counts have
    been associated with increased disease severity in COVID-19,compared with survivors (1,2), and Chen et al (3) reported that 35% of non-critical infected patients had only mild lymphocytopenia, suggesting the severity of lymphocyte depletion reflects the severity of COVID -19.

    In sum, the proposed approach would lighten the load of the otherwise congested hospitals.

    REFERENCES

    1) Ruan Q, Yang K, Wang W, Jiang L, Song J. 2020. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020. DOI:10.1007/s00134-020-05991-x.
    2) Yang X, Yu Y, Xu J, Shu H, Xia J. 2020. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020. https://doi.org/10.1016/S2213-2600(20)30079-5.
    3) Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395: 507–13.


    Arturo Tozzi
    Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA
    tozziarturo@libero.it
    Arturo.Tozzi@unt.edu
    CONFLICT OF INTEREST: None Reported
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    Behavioral factors; clinical COVID-19 exacerbation; prevention and recommendations
    Stefano Olgiati, PhD (Epidemiology) | University of Bergamo, Bergamo, Italy
    Dear Fellow Researchers,

    a. In the article, Grasselli et al (2020) report: "with predisposing factors such as race, age, and comorbidities"

    b. In the Comments, Ramadori (2020) observes that: "... the first patient with COVID-19 pneumonia is a young marathon runner of 38 year of age."

    c. Fragmented health data report that the marathon runner (and other critically or severely ill patients) practiced high performance sports and / or occupational activities during the asymptomatic and /or mild symptomatic period;

    d. Zhoukun et al (2020) report that: " ... clinical symptoms and radiological abnormalities are not
    the essential components of SARS-CoV-2 infection." and identified a sample of "...asymptomatic SARS-CoV-2 infected patients with persistent negative CT findings".

    Research Questions:

    1. Does behavior (heavy exercise, etc ) of asymptomatic or mildly symptomatic SARS-CoV-2 infected patients exacerbate the severity of COVID-19 outcomes?

    2. Should behavioral factors during the asymptomatic or mildly symptomatic period be reported / included among potential COVID-19 predisposing / clinical exacerbating factors?

    3. Should public health authorities and primary care physicians produce behavioral recommendations aimed not only at containing / mitigating the spread of COVID-19 but also at preventing a potential clinical exacerbation during incubation, mild infection period and / or quarantine ?


    Stefano Olgiati, PhD, FRSM, MSE
    stefano.olgiati@unibg.it
    s.a.olgiati@gmail.com

    REFERENCES
    1. Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. Published online March 13, 2020. doi:10.1001/jama.2020.4031

    2. Ramadori G. Mild COVID-19 Cases: Who Might Be Hospitalized And Who Can Be Quarantined? in Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. Published online March 13, 2020. doi:10.1001/jama.2020.4031

    3. Zhoukun Ling et al. Asymptomatic SARS-CoV-2 infected patients with persistent negative CT findings. European Journal of Radiology. Published:March 12, 2020DOI:https://doi.org/10.1016/j.ejrad.2020.108956
    CONFLICT OF INTEREST: None Reported
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    What about Non Invasive Ventilation in ICU/Sub-Intensive Units
    Paolo Bonazza, MD (Internal Medicine) | Karolinska University Hospital Huddinge
    First of all I send you great thanks for taking the time to share your experiences just a few days after you began to manage the COVID outbreak.

    As an internist working in a COVID high-dependency unit (HDU) is important to try to help our critical care colleagues and try to know, since the beginning of the outbreak, indications for, and other experiences with, use of non invasive ventilation.

    What do you have to say about non invasive ventilation (NIV)? Both in ICU as well HDU/Sub-intensive units. I read already that the majority of patients with advanced disease
    require intubation.

    Is non invasive ventilation with CPAP/BiPAP an alternative as a first step? Do you have any experience about that, and which modalities and pressure have you used?

    And do you have any experience with stepdown care, and NIV treatment after ICU ward?
    CONFLICT OF INTEREST: None Reported
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    What was the required number of ICU beds per 100.000 inhabitants?
    Ignacio Garcia Doval, MD, MSc Epid, PhD | Complexo Hospitalario Universitario de Vigo. Spain
    Thank you very much for this description of an impressive, and frightening, effort.

    The results would be more valuable elsewhere, and useful to plan for the emergency, if they were related to the population in the area. What is the source population of these hospitals? What was the required number of ICU beds per 100.000 inhabitants? Could the authors answer?
    CONFLICT OF INTEREST: None Reported
    ACE2 and COVID-19
    ISKANDAR MONEM ISKANDAR BASAL, medstudent | Università di Roma La Sapienza
    Today is the 23rd of March and it is the second day in which the report of the “Protezione Civile” here in Italy registers a small reduction either in the number of infected persons or the number of deaths. We all hope and intensely pray this trend to continue in the following days.

    What is happening in Italy has been actually very unusual and the heroic efforts of the Italian health system to face this tsunami of epidemic is already evident to everybody.

    However, many are asking a question. Even the JAMA Editor in his video meeting with
    Dr. Maurizio Cecconi (one of the authors) asked this question: why this odd distribution of cases? Three regions in particular were hit very severely by COVID-19.
      
    I would like if the authors allow me to share two thoughts relating to this issue:

    It is known that the SARS-CoV-2, the cause of  COVID-19 enters cell through ACE2 receptors especially on the endothelium of lung vessels and elsewhere too (1,2).

    First: Is it possible that some people have inherited a high density of ACE2 on their cells?

    Second: More probably it might be related to polymorphism. Are there some alleles of the ACE2 to which the virus attaches more easily than others which might explain the severity of the disease in some individuals?

    REFERENCES

    1. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. February 2020. doi:10.1038/s41564-020-0688-y

    2. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454. doi:10.1038/nature02145
    CONFLICT OF INTEREST: None Reported
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