Advertisement

Management and outcomes of post-acute COVID-19 patients in Northern Italy

      Keywords

      Dear Editor
      Italy is one of the most affected countries by COVID-19 pandemic which has led to dramatic effects throughout the world with millions infected people and hundreds thousand deaths. The disease can cause major alveolar damage resulting in hypoxemic acute respiratory failure (ARF), needing admission to intensive care units (ICU), continuous positive airway pressure (CPAP), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV) in a high proportion of cases [
      • Grasselli G.
      • Zangrillo A.
      • Zanella A.
      • Antonelli M.
      • Cabrini L.
      • Castelli A.
      • et al.
      COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.
      ]. Preliminary information is available in critical patients, whereas less has been reported on interventions and outcomes after the acute phase.
      The Italian regions Lombardy and Piedmont have the highest prevalence of infected people (more than 105,000 reported cases out of 14,500,000 inhabitants) resulting in shortage of ICU beds [
      • Vitacca M.
      • Nava S.
      • Santus P.
      • Harari S
      Early consensus management for non-ICU ARF SARS-CoV-2 emergency in Italy: from ward to trenches.
      ]. To free up beds in the acute care hospitals, patients with COVID-19 associated to de novo ARF, no longer requiring ICU, but still too unstable to be discharged home, were transferred to the Istituti Clinici Scientifici (ICS) Maugeri network, a multicentre referral Institution for pulmonary rehabilitation and chronic care [
      • Ceriana P.
      • Nava S.
      • Vitacca M.
      • Carlucci A.
      • Paneroni M.
      • Schreiber A.
      • Pisani L.
      • Ambrosino N
      o ventilation during weaning from prolonged mechanical ventilation.
      ]. We report the management and outcomes of patients with nasal/throat swabs still positive for SARS-CoV-2 by polymerase chain reaction, admitted to five centres (Lumezzane, Pavia, Veruno, Montescano, Tradate) of the network between March, 10th and April,30th.
      An ad hoc task force organised the hospital structures and activities to face this emergency. In and outpatient rehabilitation programs for stable non COVID-19 patients were stopped, patients discharged, and scheduled admissions delayed. A multidisciplinary team developed algorithms to drive the clinical activities in the wards. Effective protective personal equipment such as masks, N95/FFP2 respirators, gowns hair covers, gloves, eye and face shields were provided to all professionals in all occasions [

      Ippolito M., Vitale F., Accurso G., Iozzo P., Gregoretti C., Giarratano A., Cortegiani A. Medical masks and respirators for the protection of healthcare workers from SARS-CoV-2 and other viruses. Pulmonology. 2020;S2531-0437(20)30088-X. doi: 10.1016/j.pulmoe.2020.04.009.

      ].
      In addition to respiratory therapy, according to the evolving information and current research [

      N.I.H. Covid-19 Treatment Guidelines. Therapeutic options for COVID-19 currently under investigation. Available at:https://www.covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/. Accessed May11, 2020.

      ], one or more of the following drugs were added as specific therapy for COVID-19: chloroquine, antiviral, steroids, and anticoagulants. Patients underwent also the therapy for their underlying comorbidities [

      N.I.H. Covid-19 Treatment Guidelines. Therapeutic options for COVID-19 currently under investigation. Available at:https://www.covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/. Accessed May11, 2020.

      ]. Respiratory (i.e., protocols dedicated to pronation, oxygen and ventilators use) and motor physiotherapy sessions (reconditioning and physical activity as arm and/or leg cranks, low intensity aerobic exercises, walking at light-to-moderate intensity) were also proposed for at least 20 min a day [
      • Simonelli C.
      • Paneroni M.
      • Fokom A.G.
      • Saleri M.
      • Speltoni I.
      • Favero I.
      • Garofali F.
      • Scalvini S.
      • Vitacca M
      ].
      In the period under observation 907 patients were admitted and 553 of them (60.9%) were discharged. According to this definite outcome, discharged patients were considered as “ended cases” and divided in two groups: those recovered and discharged home (recovered) and those transferred to acute care hospitals or died (failure), whose data were analysed together. Results are shown in Table 1.
      Table 1Demographic, clinical characteristics, hospital history, interventions required by and outcome of 553 closed cases. Data as mean ± Standard Deviation, or numbers (%).
      RecoveredFailureP value
      Patients, n (% of discharged cases)454 (82.1)99 (17.9)0.001
      Tranferred to acute care hospitals, n (%)———32 (5.8)———
      Died patients, n (%)———67 (12.1)———
      Age, years69.1 ± 14.278.2 ± 11.20.001
      Patients younger than 60 years, n (%)136 (29.9)2 (2.0)0.001
      Male, n (%)276 (60.8)69 (69.7)0.0935
      Comorbidities per patient, n1.9 ± 1.63.3 ± 2.20.001
      Referring hospitals
      Symptom onset, days6.0 ± 3.47.1 ± 3.10.0032
      LOS, days12.8 ± 9.313.9 ± 10.30.2963
      Patients on CPAP or NIV, n (%)78 (17.2)20 (20.2)0.4770
      Patients on IMV, n (%)25 (5.5)8 (8.1)0.3406
      Tracheostomized in SB, n (%)12 (2.6)1 (1.0)0.3373
      Tracheostomized under IMV, n (%)9 (1.9)0 (0.0)0.1669
      ICS network
      LOS, days20.2 ± 13.318.3 ± 18.40.1990
      Patients under O2 therapy only, n (%)290 (63.9)74 (74.7)0.0363
      Maximal FiO2 used, (%)0.29 ± 0.120.60 ± 0.110.001
      Patients on O2 + HFNC, n (%)11 (2.4)6 (6.0)0.0589
      Patients on O2 + CPAP or NIV, n (%)36 (7.9)33 (33.3)0.001
      CPAP/NIV failure rate, n (%)0 (0.0)18 (54.5)0.001
      Discharged to telenursing, n (%)93 (20.4)
      Abbreviations: CPAP: continuous positive airway pressure; FiO2: inspiratory oxygen fraction; HFNC: high flow nasal cannula; ICS: Istituti Clinici Scientifici; IMV: invasive mechanical ventilation; LOS: length of stay; NIV: non-invasive ventilation; SB: Spontaneous breathing. Statistical methods: for continuous variable unpaired t-test and for % proportion test were conducted.
      The majority of patients were males older than sixty years, with more than one comorbidity, the failure group being older and with more comorbidities.
      These patients were still severe as shown by the high proportion of them needing oxygen, high flow nasal cannula (HFNC) or ventilatory support, by the high treatment failure requiring transferral to acute care hospitals, and high mortality rate. Indeed, out of 553 discharged cases at the end of observation, 82.1% were considered as recovered and discharged home, whereas 17.9% were either transferred to acute care hospitals (5.8%) or died (12.1%). Patients discharged home from two centres underwent a telemedicine program consisting of pulse oximetry monitoring and telenursing, telerehabilitation and second opinion consultation.
      High mortality rates are reported for patients with SARS-CoV-2 admitted to ICU [
      • Grasselli G.
      • Zangrillo A.
      • Zanella A.
      • Antonelli M.
      • Cabrini L.
      • Castelli A.
      • et al.
      COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.
      ]. This is one of the first reports on the outcomes of post-acute COVID-19 patients and the high mortality rate indicates that even when patients are discharged from acute care hospitals, their conditions may still be severe and require monitoring and complex interventions. Patients of two groups required oxygen supplementation in a similar proportion, whereas died and transferred patients required more non-invasive ventilator support. Guidelines give indications regarding the use of non-invasive ventilatory support to avoid IMV, with some advocating HFNC over NIV or vice versa [

      World Health Organization. (2020). Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020. World Health Organization. https://apps.who.int/iris/handle/10665/330893. Accessed May 11, 2020.

      ,
      • Alhazzani W.
      • Møller M.H.
      • Arabi Y.M.
      • Loeb M.
      • Gong M.N.
      • Fan E.
      • Oczkowski S.
      • Levy M.M.
      • Derde L.
      • Dzierba A.
      • Du B.
      • Aboodi M.
      • Wunsch H.
      • Cecconi M.
      • Koh Y.
      • Chertow D.S.
      • Maitland K.
      • Alshamsi F.
      • Belley-Cote E.
      • Greco M.
      • Laundy M.
      • Morgan J.S.
      • Kesecioglu J.
      • Mc Geer A.
      • Mermel L.
      • Mammen M.J.
      • Alexander P.E.
      • Arrington A.
      • Centofanti J.E.
      • Citerio G.
      • Baw B.
      • Memish Z.A.
      • Hammond N.
      • Hayden F.G.
      • Evans L.
      • Rhodes A
      Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
      ]. There have been no randomized control trials on the use of either HFNC or NIV in coronavirus-related pneumonia to avoid intubation, and even less information is reported on the use of these tools after the acute phase. This issue is particularly important as all modalities of non-invasive ventilatory support or even simple oxygen supplementation via cannula can be a source of aerosol contamination [
      • Simonds A.K.
      • Hanak A.
      • Chatwin M.
      • Morrell M.
      • Hall A.
      • Parker K.H.
      • Siggers J.H.
      • Dickinson R.J
      Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.
      ]. Recently, in these patients it has been proposed to add prone position while performing NIV [

      Longhini F., Bruni A., Garofalo E., Navalesi P., Grasselli G., Cosentini R., Foti G., Mattei A., Ippolito M., .G. Accurso G., Vitale F., Cortegiani A., Gregoretti C. Helmet continuous positive airway pressure and prone positioning: a proposal for an early management of COVID-19 patients. Pulmonology2020;S2531-0437(20)30094-5. doi: 10.1016/j.pulmoe.2020.04.014.

      ].
      Our patients underwent also medical therapy with drugs claimed, but not proven, to be successful for treating COVID-19. Despite patients did not complain any adverse effect, at present no drug has been approved or proven to be safe and effective to treat these patients. Definitive clinical trials are needed to identify optimal treatments [

      N.I.H. Covid-19 Treatment Guidelines. Therapeutic options for COVID-19 currently under investigation. Available at:https://www.covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/. Accessed May11, 2020.

      ].
      Our patients underwent also short sessions of reconditioning and physiotherapy. Despite fatigue is a highly prevalent symptom in patients with COVID-19 infection and most of the hospitalized COVID-19 patients have a prolonged length of stay in ward, the effect of muscle activity in the course of viral infections is unknown. Many countries have had a complete lockdown, preventing participation in regular rehabilitation programs in most outpatient centers and/or the delivery of home programs or other individualized treatments. Telemedicine can be a useful tool to obviate this problem, however, only one fifth of discharged patients could undergo such modality.
      What lesson can we learn? The pathophysiology of COVID-19 inducing ARF requires high skill by physicians and other professionals. Besides providing the proper safety equipment, an appropriate use of available technologies is required. Robots, Artificial Intelligence, Big Data Analytics, mobile apps and telemedicine will be effective resources in fighting pandemic [
      • Mazzoleni S.
      • Turchetti G.
      • Ambrosino N
      The COVID-19 outbreak: from “black swan” to global challenges and opportunities.
      ].
      In conclusion, this letter provides characteristics and outcomes of post-acute patients with confirmed COVID-19 in Northern Italy. These patients are still a challenge for the health system due to high need of monitoring, complex respiratory support, high risk of further decompensation and death.

      Funding

      This work was supported by the “Ricerca Corrente” funding scheme of the Italian Ministry of Health.

      Declaration of Competing Interests

      Authors do not report any conflict of interest.

      Acknowledgement

      We thank Laura Comini for technical assistance and editing.

      References

        • Grasselli G.
        • Zangrillo A.
        • Zanella A.
        • Antonelli M.
        • Cabrini L.
        • Castelli A.
        • et al.
        COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.
        JAMA. 2020; 323: 1574-1581https://doi.org/10.1001/jama.2020.5394
        • Vitacca M.
        • Nava S.
        • Santus P.
        • Harari S
        Early consensus management for non-ICU ARF SARS-CoV-2 emergency in Italy: from ward to trenches.
        Eur Respir J. 2020; 552000632https://doi.org/10.1183/13993003.00632-2020
        • Ceriana P.
        • Nava S.
        • Vitacca M.
        • Carlucci A.
        • Paneroni M.
        • Schreiber A.
        • Pisani L.
        • Ambrosino N
        o ventilation during weaning from prolonged mechanical ventilation.
        Pulmonology. 2019; 25: 328-333https://doi.org/10.1016/j.pulmoe.2019.07.006
      1. Ippolito M., Vitale F., Accurso G., Iozzo P., Gregoretti C., Giarratano A., Cortegiani A. Medical masks and respirators for the protection of healthcare workers from SARS-CoV-2 and other viruses. Pulmonology. 2020;S2531-0437(20)30088-X. doi: 10.1016/j.pulmoe.2020.04.009.

      2. N.I.H. Covid-19 Treatment Guidelines. Therapeutic options for COVID-19 currently under investigation. Available at:https://www.covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/. Accessed May11, 2020.

        • Simonelli C.
        • Paneroni M.
        • Fokom A.G.
        • Saleri M.
        • Speltoni I.
        • Favero I.
        • Garofali F.
        • Scalvini S.
        • Vitacca M
        Monaldi Arch Chest Dis. 2020; 90https://doi.org/10.4081/monaldi.2020.1085
      3. World Health Organization. (2020). Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020. World Health Organization. https://apps.who.int/iris/handle/10665/330893. Accessed May 11, 2020.

        • Alhazzani W.
        • Møller M.H.
        • Arabi Y.M.
        • Loeb M.
        • Gong M.N.
        • Fan E.
        • Oczkowski S.
        • Levy M.M.
        • Derde L.
        • Dzierba A.
        • Du B.
        • Aboodi M.
        • Wunsch H.
        • Cecconi M.
        • Koh Y.
        • Chertow D.S.
        • Maitland K.
        • Alshamsi F.
        • Belley-Cote E.
        • Greco M.
        • Laundy M.
        • Morgan J.S.
        • Kesecioglu J.
        • Mc Geer A.
        • Mermel L.
        • Mammen M.J.
        • Alexander P.E.
        • Arrington A.
        • Centofanti J.E.
        • Citerio G.
        • Baw B.
        • Memish Z.A.
        • Hammond N.
        • Hayden F.G.
        • Evans L.
        • Rhodes A
        Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
        Intensive Care Med. 2020; 46: 854-887https://doi.org/10.1007/s00134-020-06022-5
        • Simonds A.K.
        • Hanak A.
        • Chatwin M.
        • Morrell M.
        • Hall A.
        • Parker K.H.
        • Siggers J.H.
        • Dickinson R.J
        Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.
        Health Technol Assess. 2010; 14: 131-172https://doi.org/10.3310/hta14460-02
      4. Longhini F., Bruni A., Garofalo E., Navalesi P., Grasselli G., Cosentini R., Foti G., Mattei A., Ippolito M., .G. Accurso G., Vitale F., Cortegiani A., Gregoretti C. Helmet continuous positive airway pressure and prone positioning: a proposal for an early management of COVID-19 patients. Pulmonology2020;S2531-0437(20)30094-5. doi: 10.1016/j.pulmoe.2020.04.014.

        • Mazzoleni S.
        • Turchetti G.
        • Ambrosino N
        The COVID-19 outbreak: from “black swan” to global challenges and opportunities.
        Pulmonology. 2020; 26: 117-118https://doi.org/10.1016/j.pulmoe.2020.03.002