Quality of Life and Physical Performance After Novel Coronavirus Infection (COVID-19);
Quality of Life and Physical Performance After Novel Coronavirus Infection (COVID-19);
This study aims to observe the long-term health-related quality of life (HRQOL) and physical
 performance in individuals hospitalized due to a COVID-19 infection. Therefore, data is
 extracted from a study-site standard aftercare program which has been adjusted for this
 patient population. This comprehensive aftercare program includes education sessions and
 physical exercise. A second aim is to observe adherence and feasibility to the program and if
 indicated compare the clinical data and outcomes from patients following the program with
 patients denying to participate in guided exercise and education sessions.

 It is expected that patients hospitalized due to COVID-19 infection show a reduction in
 physical performance and HRQOL directly after discharge. The severity of illness is
 hypothesized to be associated with a reduction as well in HRQOL and physical performance
 after one-year post-discharge.
Currently, the U.S. National Library of Medicine (April 2nd) reports 282 studies registered
 investigating the COVID-19 infection. According to the present knowledge the COVID-19, also
 known as novel type Coronavirus or SARS-CoV-2 (severe acute respiratory
 syndrome-Coronavirus-2), belongs to a large family of viruses consist-ing of hundreds of
 variations and subtypes of this virus (World Health Organisation (WHO)/emergencies, April 2nd
 2020). These types of virus' can cause respiratory and gastrointestinal symptoms ranging from
 a mild cold to pneumonia. The clinical manifestation of this novel type of Coronavirus -
 COVID-19 - was found to cause more severe pneumonia or severe acute respiratory syndrome such
 as the acute respiratory distress syndrome (ARDS). According to the data of Arabi and
 colleagues (2020) average age in Chinese affected individuals were 60, 40% had comorbid
 conditions, 42% required invasive mechanical ventilation and the mortality rate was at 62%.
 Epidemiological information from other countries is not yet published. According to the WHO
 in the Europe Region, 503730 cases and 33617 deaths were reported since January 25th 2020. In
 the 8,5 million populated countries of Switzerland, the number of confirmed cases raised to
 23'574 and 756 deaths (Bundesamt für Gesundheit) Situationsbericht, April 9th). According to
 this report, the incidence of infection and hospitalization is highest in individuals aged 50
 and older with a higher presence registered in men. Nevertheless, a certain number of
 affected individuals is between 20 and 50 years which is in accordance with the number
 presented from large studies in China (50.7%-55.1%). Among the 23'674 positive tested 2730
 are currently hospitalized. Among these 280 individuals require mechanically assisted
 ventilation, meaning health care at an intensive care unit (status April 2nd).

 In this acute situation of the pandemic, there is an enormous urge to finding a vaccine or
 medications to release or prevent severe symptoms and complications due to the new virus.
 Therefore, in the listed studies keen interest is on drug interventions to stop the expansion
 of this virus. However, knowledge on long-term consequences of physical condition and
 psychological state is unknown. Although, taking into account the clinical manifestation
 observed in the severe cases negative long-term consequences have to be expected as described
 in the following paragraph.

 Up to date knowledge exist on the clinical manifestation which varies from asymptomatic to
 severe disease with approximately 80% of the cases found to present an asymptomatic carrier.

 Thus, about 13.8% to 35% is suffering a severe course including dyspnoea, respiratory
 frequency ≥30/minute, desaturation of blood oxygen (≤93%) and or lung infiltrates >50% of the
 lung within 24-48 hours. Further signs of hospitalized individuals are fever, cough, myalgia,
 fatigue and sputum production. In literature, the clinical picture is described as bilateral
 pneumonia or acute respiratory distress syndrome which leads to a severe organ failure of the
 lung. These patients require oxygen therapy with invasive (17%) or non-invasive (14%)
 mechanically assisted ventilation. And the higher probability of preloaded organ dysfunctions
 due to co-morbidities most often high blood pressure (13%), diabetes (4-6%) and COPD (1-5%)
 has to be taken into account.

 According to the WHO report and Lai et al (2020) between 6.1% to 28%, respectively, were
 found to be in a critical stage. Acute respiratory failure, septic shock and/ or multiple
 organ failure defined this stage. According to a retrospective analysis from a large
 population in Wuhan, these patients require intensive care with most of them presenting
 (multi) organ failure with acute respiratory distress (ARDS, 67%), acute kidney injury (29%),
 cardiac injury (23%), and liver dysfunction (29%). These patients require invasive or
 non-invasive mechanical ventilation. The mortality rate for critically ill COVID-19 patients
 varies from 1-4% to 4.3% according to large studies reported by Lai et al. (2020).

 According to these statistics, about 4.3% of the 280 patients requiring intensive care in
 Switzerland (n=12) would not survive. Taking the current number of 2730 hospitalised patients
 reported above, these statistics result in about 2718 individuals surviving severe illness in
 Switzerland. A critical point is the high risk of the length of stay on the ward as explained
 in the following paragraph.

 Patients in the severe and critical state are likely to suffer prolonged length of stay in
 the hospital according to Lia et al. (2020) and Wang et al. (2020) (±21 days). Studies on
 ARDS and critically ill patients led to strong evidence that prolonged length of stay,
 particularly with prolonged mechanical ventilation, leads to a significant negative impact on
 lung function, physical activity and emotional state. For example, from 109 patients suffered
 an ARDS (age interquartile from 35 to 57) the 5 years follow up showed a relevant reduction
 on physical condition (76% of the distance in the 6 Minute Walk Test (6MWT)) when compared to
 age and sex-matched norm values. Interestingly, these deficits were found despite normal to
 "near"-normal pulmonary function. A recent post-hoc analysis on 116 patients mechanically
 ventilated for at least >24h showed that a longer duration of mechanical ventilation and
 exposure to norepinephrine were associated with intensive-care-unit acquired weakness
 (ICU-AW; defined as <48/100 on the Medical Research Council Score). Hatch et al. (2018) for
 example found in their multicenter follow-up study, that 46% of the survivors of critical
 illness suffered from anxiety, 40% from depression and 22% from post-traumatic stress
 disorder (PTSD). In the specific population of ARDS survivors (n=74) numbers are slightly
 lower ranging from moderate to severe depression in 16% and 23%, respectively and for anxiety
 24% and 23% at 1 and 2 years, respectively. These findings on survivors of ARDS and critical
 illness underline the assumption that survivors of a COVID-19 induced hospitalized will
 suffer from physical and psychological long-term consequences.

 In research on critical illness post-ICU, only moderate evidence and large risk of bias exist
 on the effect of follow-up rehabilitation post-ICU. However, some qualitative studies support
 the thought that patients might need additional care after discharge home. King et al. (2019)
 investigated in their scoping review of qualitative studies the needs of critical illness
 survivors and found that after discharge home patients had continuing information needs on
 understanding their critical illness and coping with the long-term sequelae and stress.

 These qualitative findings were underlined and supported by quantitative studies
 investigating long-term effects in this population. In patients who suffered an acute
 respiratory failure greatest change in physical function was found two months after
 discharge. And in ICU survivors requiring one or more weeks of mechanical ventilation the
 degree of disability one week after ICU discharge was predictive for physical and mental
 recovery and mortality in the one-year follow up.

 In contrast to the findings on critical illness aftercare programs were found having a
 positive impact in a population with pulmonary disease. In survivors of ARDS due to severe
 influenza, A pneumonitis an 8-week pulmonary rehabilitation program improved significantly
 exercise capacity and quality of life improved significantly. And in patients with chronic
 obstructive pulmonary disease (COPD), the American Thoracic Society recommends respiratory
 rehabilitation early after discharge. Furthermore, according to the NICE guidelines
 "Rehabilitation after critical illness in adults" patients with rehabilitation needs should
 be seen two to three months after hospital discharge and should be reassessed to establish
 health and social care needs.

 Additionally, based on an expert consensus following questions are still unanswered and
 considered as being relevant for the rehabilitation of these patients. Some examples are
 listed below:

 -  "What proportion of COVID-19 survivors have (extra-pulmonary) physical, functional,
 emotional and sociable treatable traits, justifying rehabilitation…?"

 -  "What types of patients will exist post-COVID-19 (e.g. good recovery, frailty,
 persistent respiratory impairment) and in what proportion?"

 -  "What is the impact of a COVID-19-related prolonged ward stay on physical and emotional
 functioning?

 -  What are the opportunities to intervene early, immediately post-acute hospital
 discharge?

 -  For how long after hospital discharge are COVID-19 survivors contagious? The latter two
 questions are cardinal to provide safe and feasible rehabilitation post-acute hospital
 discharge. To present the feasibility and safety of the aftercare program developed and
 conducted on the study site a short excurse on literature is provided.

 Recent knowledge (published February 28 and 1st of April) from high impact journals give
 following solid time frames on viral shedding according to the traceability of Covid-19 RNA.
 Reverse transcription-polymerase chain reaction (RT-PCR) of virus RNA was used to measure the
 quantity of virus RNA in both studies.

 Wölfel and colleagues isolated the virus daily from sputum, pharyngeal swabs, and stool since
 the first day of symptom onset. The samples were taken from individuals with mild to moderate
 symptoms (e.g. symptoms of lung affection). Maximal viral load was found before 5 days in
 these participants with the mild course being highest in stool and sputum. Based on their
 findings authors state that being 10 days beyond symptoms and less than 100,000 viral RNA
 copies per ml of sputum do have a little residual risk of infectivity, based on cell culture.
 Ling et al., isolated viral RNA from 66 participants post-Covid-19 infection as well from the
 stool, urine, and blood specimens during the convalescence. These samples were obtained from
 patients who survived a severe course of infection. The longest duration from onset of
 symptoms to first negative RT-PCR results for oropharyngeal swabs of convalescent patients
 was 22 days.

 Zhou et al. (2020) studied as well the viral shedding with the daily analysis using PCR of
 Covid-19 throat swab specimens from 191 patients. For survivors, the duration of viral
 shedding showed an interquartile range of 17 to 22 days in patients with severe disease
 status (survivors). In summary, current knowledge shows the duration of viral traceability
 and thus the risk of infection from 10 to 22 days in patients with mild and severe illness,
 respectively. The average time to incubation found ranged from 5.2 to 12.5 days (Zhou et al.,
 2020) and average hospital duration ranged from 7 to 15 days in the 425 patients from Wuhan.

 Therefore, subtracting lowest period of incubation (5 days) from the maximal duration of
 viral shedding (22 days) resulting in 17 days after first confirmed diagnose to be safe for
 hospital on-site testing. Based on this data and adding the criteria 4 days without specific
 COVID-19 symptoms (described in chapter 6.2.1), the committee developing the specific
 aftercare program - from which data will be taken for this study - considered as safe and
 feasible inviting patients post-acute hospital discharge when 14 days post diagnose and the
 mentioned four days (total ≥18 days).

 In summary, there is a lack of knowledge on long term consequences of physical, emotional and
 quality of life outcomes. The similarity of clinical manifestation of the COVID-19 infection
 with ARDS or/and critical illness leads to the consideration of evidence found in this
 patient population. This evidence points out the high risk of long-term deficits on the
 above-mentioned outcomes and the relevance of patient-tailored rehabilitation programs.

 Therefore, we consider it as essential to gather and analyse data on short and long-term
 quality of life and physical performance of patients after hospitalization due to COVID-19
 infection.
Inclusion Criteria:

 -  Hospitalized at the Kantonsspital Winterthur (KSW) due to COVID-19 infection
 (laboratory-confirmed),

 -  with or without mechanically assisted ventilation

 -  being at risk to obtain severe illness caused by the COVID-19*

 -  individuals without defined risk factors but requiring oxygenation during
 hospitalisation

 -  Agree to general consent or specific consent to subsequent use of his/her personal
 health data for research purpose

 -  German-speaking

 Exclusion Criteria:

 -  Presence of mental disability or impairments to reasoning or judgment

 -  Individuals who are immunocompromised due to medical treatment

 -  A documented objection of subsequent use of personal health data

 Specific exclusion criteria for presence at the hospital (for evaluation and training);
 criteria will be verified during the phone-based screening process. After two weeks of a
 COVID-19 positive diagnosis and with four entire days the patient reports no signs of:

 -  fever >37.3° C

 -  sore throat,

 -  cough (productive or non-productive)

 -  common cold

 Also, treatment-based immunocompromised patients are excluded for on-site evaluation and
 training.