Additional Clinical Expertise for Treatment of Severely Ill ICU Patients Needed
Giuliano Ramadori, Professor of Medicine | University Clinic,Internal Medicine,Göttingen,Germany
The priorities listed for responding to COVID-19 are of general interest and not only for the US Health community.Thank you to the authors for having put together the experiences made by past epidemics and the Chinese experience. I also fully agree with the sentence „Because some proportion of patients will be severely ill and require critical care interventions, specific preparation is needed in ICUs“. As many of the critically ill patients are > 60 years old, they suffer from many „internists'“ (comorbid) conditions — chronic diseases like diabetes, NAFLD, and chronic kidney disease, and many of them also take at least 3 different drugs every day.
For correct treatment of these patients it is not sufficient to try to optimize respiratory function with different technologies like ECMO but it is mandatory to know how to protect other vital organs aside from the lung. In fact it has not yet been demonstrated in any of the past coronavirus epidemics (SARS, MERS) that the virus induces loss of organ function by directly infecting those organs. (1)
Treatment by interdisciplinary medical teams would be the best for those patients.
I also would like to suggest to avoid use of „experimental“ drugs outside of well planned clinical trials in critically ill patients.
1. Liu J,Zheng X, Tong Q, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-Cov, and 2019-cCoV. J Med Virol 2020; February 13:1-4.
CONFLICT OF INTEREST: None Reported
March 24, 2020 COVID 19:
IS COMPARISON WITH CHINA SO IMPORTANT?
Giuliano Ramadori, Professor of Medicine | University clinic ,Internal Medicine,Göttingen,Germany
The Italian patient number one (38 year old) has just been released from the hospital San Matteo. His pregnant wife, who was also infected, was already at home.The patient`s father, however, unfortunately died of COVID-19. We are informed by very transparent Italian journalism. This makes comparison of numbers coming from other countries around the world very difficult.
On the other hand it is important to focus on Italian numbers which mostly come from Lombardy. In some of the areas of Lombardy, the number of deaths are five times higher compared with those of the same period of last year. This in a region with the best health care system in Italy. What went wrong? This is the question politicians will have to answer as soon as the pandemic will be over.
April 2, 2020
Sporting Event in Lombardy and COVID-19 Viral Transmission Giuliano
Ramadori, Professor of Medicine | University Clinic,Internal Medicine,Göttingen,Germany
The soccer fight Atalanta Bergamo against Valencia which took place in Milan on February 19 may become a milestone in the history of epidemiological studies. About one third of the population of Bergamo attended the match. One can only imagine what happened in Bergamo when the fans went back to Bergamo from Milan after their team had won the match.
On march 16 th the news paper La Repubblica published an article :Spagna,Valencia:“ il 35% di noi positivi dopo aver giocato a Milano“ („35% of us are positive after playing in Milan).
Two days after the match the first (official) COVID 19-positive patient appeared at the Codogno-Hospital because of influenza-like symptoms. He was patient number 1 in Italy while a Chinese couple was treated in Rome since the 28 th of January. At the same time however, a 78 year-old man in Vó Euganeo fell ill on February 20th and died the next day of COVID-19 infection. He was the first person in Italy who died of the COVID-19. The area around Codogno (about 50.000 inhabitants) and the area around Vó were locked down, but not the area around Bergamo (ca 1.3 million people).
The number of new infections became such that the doctors at the university hospital in Bergamo, Papa Giovanni Paolo II, did not have time to decide who should be treated by mechanical ventilation.This was mainly because the Italian health care system does not have intermediate structures between home doctors and the hospitals.
While in Codogno only symptomatic persons were tested for COVID 19-infection ( all 78 chinese citizens were negative), all the inhabitants of Vó Euganeo,a town near Padova, 3.500 persons, were tested and asked to stay home. Seventy persons were tested positive at the beginning of the 14-day quarantine and seven of them were still COVID-19 positive when the quarantine was officially terminated. Eight Chinese citizens were negative (1)
As far as I know none of the positive persons became ill (with the exception of the 78 year old man who died first) during the quarantine. The experience of VÒ demonstrates that there are asymptomatic persons who can transmit the virus.It also demonstrates that quarantine may help to avoid the the appearence or worsening of symptoms in infected persons bevfre the virus is eliminated.
Two regions, Lombardy and Veneto, close to each other, each have two different approaches with different epidemiology. As of 01.04.2020 (April 1), the Veneto has tested 112,000 persons and found 9625 COVID-19-positive persons; 1,718 have been hospitalized and 350 are being treated at an ICU. Lombardy has tested 121,000 persons and 44.773 were positive,11927 are hospitalized and 1342 are being treated at the ICU.
The lesson is to test as many persons as possible.If one needs to choose whom to test then it should begin with workers in the different health care structures.
REFERENCE 1.These zu Corona Herkunft. Brachten Chinesen das Virus nach Italien? Tageschau.de.26.03.2020. www.tagesschau.de › faktenfinder › italien-coronavirus-china-101
CONFLICT OF INTEREST: None Reported
March 14, 2020
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.
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 READ LESS
March 14, 2020
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.
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 firstname.lastname@example.org Arturo.Tozzi@unt.edu CONFLICT OF INTEREST: None Reported READ MORE March 15, 2020
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“.
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 ?
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 READ MORE
March 19, 2020
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 READ MORE
March 20, 2020
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 March 23, 2020 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?
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 READ MORE
November 29, 2020
HCoV-2-Infection: early supportive care (pre-hospitalisation period) is crucial to avoid second period of illness.
Giuliano Ramadori, Professor of Medicine | University Clinic, Internal Medicine, Göttingen, Germany.
CONFLICT OF INTEREST: None Reported
Most of the clinical data published so far have been obtained by analysing charts from hospitalized patients with little gain of knowledge concerning the treatment strategy of symptomatic patients during hospitalisation. References 5-7 in this Viewpoint give little information about the early phase of the infection (in the pre-hospitalisation period) which however may lead patients to the emergency room and to hospitalisation with severe consequences.
At this stage supportive care is crucial before starting experimental therapy (2,3).
Dr Tomera above suggests that biochemical and immunological parameters could predict the outcome, but albumin serum level is a very important prognostic marker that is not on his list (4). The publications of the Tomera`s group (5-8) have however seminal value not only because of the possible importance of the administration of a COX-2-inhibitor (9,10) together with the histamine-2- receptor inhibitor famotidine but also and most importantly because of the repeated determination of the creatinine and eGFR which shows improvement during hospitalisation and points toward use of fluid administration to the studied patients as supportive care (2,3). This procedure has not been stressed highly enough in guidelines but may be worth further study as all the severely ill patients in the Tomera`s study could be released from the hospital.
1.Datta SD,et al. JAMA 2020,nov.18 2.Ramadori G JAMA,2020;323(4):2464-2466(comment) 3.Ramadori G,JAMA,2020 june 20 (comment) 4.Ramadori G,Hepatoma res.2020,jun 3 5.Tomera K,JAMA 2020; nov 18 (comment) 6.Tomera K,Kittah JTrialSitenews2020,July 31 7.Tomera K,Kittah J,Preprints 2020 August 24 8.Tomera K,Kittah J SSRN 2020,oct 1(revised) 9.Amici C et al.Antiviral Therapy 2006;11:1021-1030 10.Tuveson D et al.TrialSitenews 2020,Jun 7
L´arrivo delle belle stagioni di primavera ed estate ci riportano alla mente con piu´forza quanto sia importante avere abbastanza acqua dolce adisposizione. Questo anche perche´ in diversi casi in cui l´acqua significava energia essa e´stata sostituita dall`energia elettrica.In altri casi come quello dell ´irrigazione dei campi essa e´scomparsa dalla superficie e ora scorre all´interno di tubature che ne´riducono la dispersione. Si puo´quasi affermare che Il tenna e` rimasto l´ultimo testimone di quanto l´acqua „pulita“ sia importante non solo per la produzione delle fonti principali del nostro nutrimento e del nutrimento dei nostri animali,come cereali,verdure e frutta. Anche se attualmente molta della produzione agricola di un tempo e´stata „smantellata“ e il territorio un tempo agricolo e´stato in parte „cementificato“ dobbiamo ricordarci
che quello che ora ci resta a disposizione deve essere conservato con cura sia che esso sia ancora coltivato o che esso sia stato in parte abbandonato.
A questo proposito c´e´e ci sara´bisogno dell´acqua „pulita“.E`molto importante che ci sia acqua potabile a disposizione al di fuori delle mura domestiche in diversi punti del territorio.
Per turisti che vogliono visitare il nostro territorio,fare una sosta presso una sorgente di acqua potabile rappresenta una occasione di riposo e una fonte di ristoro.
Ogni persona che sia essa adolescente o adulta abbisogna in condizioni normali da 1.5 a 2,5 litri di acqua al giorno.Per molti giovani e´diventato abituale portre con se acqua in bottiglia in quantita´diverse a seconda delle ore da trascorrere fuori di casa e dell`attivita´che si vuole svolgere.
La persona di eta´magari oltre i settanta anni e´cronicamente „disidratata“ e magari sente di meno il senso della sete.
La mancanza acuta di acqua specialmente in queste persone provoca una serie di disturbi come, vertigini,senso di spossatezza, confusione mentale e anche cadute con conseguenze che possono essere gravi e condurre all´ospedalizzazione dove magari la causa principale della caduta non viene neanche presa in considerazione.
Nel caso della attuale pandemia da SARS-CoV-2 (COVID-19) la disidratazione e´la causa principale dei disturbi che ormai tutti conosciamo , che attribuiamo all´azione diretta del virus e che possono condurre all`ospedalizzazione.Qualche volta questo puo´succdere perfino dopo che il virus e´stato eliminato.
Il virus che magari si manifesta all´inizio con un semplece raffreddore e tosse secca provoca spesso non solo perdita del gusto e dell´olfatto ma anche febbre che puo´arrivare a 39-40 gradi e persistere per diversi giorni.La febbre aggrava di molto la disidratazione che porta poi alla sonnolenza,e perfino perdita di coscienza e riduzione acuta dell´apporto di calorie con la dieta.Si mette in moto un circolo vizioso che deve essere interrotto subito appena compaiono i primi sintomi.
Potrebbe essere successa una cosa simile al giocatore danese ERIKSEN.
Infatti l´aritmia cardiaca come causa dell´arresto cardiaco e` una delle possibili cause della caduta dellatleta alla fine del primo tempo della patita.
In questo frangente l´acqua diventa un „farmaco“ salvavita.
Non e´pero´superfluo ricordare che,durante questa fase non bisogna dimenticare la nutrizione. Questo non solo come apporto calorico ma e soprattuto per l´apporto proteico che e´indispensabile per la produzione di importanti proteine del sangue.La piu´
Importante di queste e´l´albumina che trattiene l´acqua nei vasi e e´responsabile (insieme all´acqua) a mantenere la pressione sanguigna che „ci tiene in piedi“.