Editor—Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) was first reported in December 2019. Although most patients
have a favourable evolution, some patients have worse outcomes, progressing to acute
respiratory distress syndrome (ARDS) and requiring treatment in an ICU.1, 2, 3, 4
Patients who survive may be susceptible to developing poor health-related quality
of life (HRQoL) and persistent symptoms after ICU discharge; however, this has not
been investigated. The present study aimed to determine the quality of life, functional
status, and persistent symptoms of patients with COVID-19-induced ARDS at 6 months
after requiring treatment in an ICU. The ethics committee of Galicia, Spain (code
No. 2020-188), approved this study. Informed consent was obtained from all participants.
We prospectively evaluated all critically ill patients with COVID-19-induced ARDS
admitted to the ICUs of seven hospitals located in northwestern Spain between March
15 and April 30, 2020. A confirmed case of COVID-19 was defined by a positive result
on a reverse-transcriptase polymerase chain reaction (RT–PCR) test. The following
information was collected during ICU admission: patient characteristics, coexisting
disorders, treatments, complications, Acute Physiology and Chronic Health Evaluation
II (APACHE II) score, laboratory tests, need for mechanical ventilation, tracheotomy,
renal replacement therapy, duration of mechanical ventilation, length of ICU stay,
and ICU outcomes.
All patients who survived ICU admission were included to assess HRQoL, functional
status, and persistent symptoms using a structured interview conducted by designated
trained research coordinators at participating sites, 6 months after requiring ICU
treatment. Patients were asked to recount their quality of life and functional status
3–6 months before COVID-19 at the time of the interview. HRQOoL was assessed using
the EuroQol Group Association five-domain, three-level questionnaire (EQ-5D-3L), which
consists of two sections: the descriptive system and the visual analogue scale. The
descriptive system assesses five domains: mobility, self-care, usual activities, pain/discomfort,
and anxiety/depression, with three possible responses options: no problems, some problems,
or extreme problems. The individual domains were converted to a utility score (EQ-5D
index), a continuous range from –0.59 to 1.00, with 1.00 indicating ‘full health’
and 0 representing death. The visual analogue scale (EQ-VAS) represents 0 = worst
imaginable health and 100 = best imaginable health.
5
Functional status was assessed according to the recently described Post-COVID-19 Functional
Status scale (PCFS).
6
Persistent symptoms potentially correlated with COVID-19 were also obtained. All analyses
were performed using R (version 4.0.2; R Foundation for Statistical Computing, Vienna,
Austria) and IBM SPSS (version 26; SPSS, Inc, Chicago, IL, USA). The quantitative
variables are expressed as median (inter-quartile range [IQR]) or median (standard
deviation [sd]) and categorical variables as number (%).
During the study period, 120 critically ill COVID-19 ARDS patients were admitted to
the ICUs. Among the 120 patients, 23 (19%) died during ICU admission, and 5 within
the first 6 months after ICU discharge. Ninety-two patients were potentially eligible
for the 6 month follow-up assessment. One patient declined to participate. Therefore,
91 patients were included. Supplementary Table S1 displays the patient characteristics
and clinical course during ICU stay of the study population.
Of the 91 survivors at 6 month interview, a decrease in the quality of life was observed
among 61 (67%) patients. The proportions of patients with moderate to extreme problems
in the five dimensions studied with the EQ-5D-3L were mobility (56%), usual activities
(37%), self-care (13%), pain/discomfort (48%), and anxiety/depression (46%) (Table 1
).
Table 1
Quality of life and functional status of the study sample (n=91). Data are expressed
as n (%) or mean (standard deviation). Quality of life was measured using the EuroQol,
five-dimension, three-level questionnaire and the EQ-VAS (0–100). Functional status
was measured using the Post-COVID-19 Functional Status scale. Means for continuous
variables were compared using unpaired or paired t-tests when the data were normally
distributed; otherwise, the Mann–Whitney U-test or Wilcoxon test was used. Proportions
for categorical variables were compared using Pearson's χ2 test or McNemar's test
as appropriate. All tests were two-sided with a significance level of P<0.05. EQ-VAS,
EuroQol visual analogue scale; EQ-5D-3L, EuroQol Group Association five-domain, three-level
questionnaire.
Table 1
Before COVID-19
6 months after COVID-19
P value
Quality
of life (EQ-5D-3L)
Characteristics
Mobility
No problems
85 (93.4)
40 (44.0)
<0.001
Some problems
6 (6.6)
51 (56.0)
Unable to walk
0 (0.0)
0 (0.0)
Self-care
No problems
91 (100.0)
79 (86.9)
<0.001
Some problems
0 (0.0)
10 (11.0)
Unable to wash or dress myself
0 (0.0)
2 (2.2)
Usual activities
No problems
90 (98.9)
57 (62.6)
<0.001
Some problems
1 (1.1)
24 (26.4)
Unable to perform
0 (0.0)
10 (11.0)
Pain or discomfort
No pain or discomfort
81 (89.0)
47 (51.6)
<0.001
Some pain or discomfort
10 (11.0)
36 (39.6)
Extreme pain or discomfort
0 (0.0)
8 (8.8)
Anxiety or depression
Not anxious or depressed
85 (93.4)
49 (53.8)
<0.001
Moderately anxious or depressed
6 (6.6)
38 (41.8)
Extremely anxious or depressed
0 (0.0)
4 (4.4)
EQ-5D index
0.9655 (0.0958)
0.7054 (0.2514)
<0.001
EQ-VAS (0–100)
87.58 (11.68)
66.36 (18.26)
<0.001
Post-COVID-19 Functional Status scale
Grade
0: No limitations in my everyday life.
77 (84.6)
28 (30.8)
<0.001
1: Negligible limitations, (still have persistent symptoms).
13 (14.3)
22 (24.2)
2: Limitations in my everyday life, and occasionally need avoid or reduce usual activities.
1 (1.1)
20 (22.0)
3. Limitations in my everyday life, and I am not able to perform all usual activities.
0 (0.0)
16 (17.6)
4. Severe limitations. I am dependent on another person because of symptoms.
0 (0.0)
5 (5.5)
At the 6 month interview, 57 (63%) patients reported decreased functional status.
Thirty-five (38%) patients had lowered two grades in the PCFS, and 41 (45%) patients
described persistent functional limitations (grades 2–4 in the PCFS) (Table 1).
Advanced age, male sex, need for mechanical ventilation during ICU stay, duration
of mechanical ventilation, length of ICU stay, and length of hospital stay were associated
with a decreased quality of life, decreased functional status at 6 months after ICU
admission, or both (Supplementary Table S1).
Supplementary Table S2 shows persistent symptoms potentially correlated with COVID-19
observed in the 91 patients. At the 6 month evaluation, a high proportion of patients
reported dyspnoea on exertion (57%), asthaenia (37%), myalgia (37%), and arthralgia
(29%). Only 15 (16%) patients were completely free of persistent symptoms.
To our knowledge, this study represents the first description of the long-term health-related
outcomes in survivors of COVID-19-associated ARDS. We found that at 6 months after
requiring ICU admission, a large proportion of them had worsened quality of life,
diminution of the functional status, and persistent symptoms compared with their pre-COVID-19
status. These data are consistent with prior studies that report poor long-term outcomes
in critically ill survivors of ARDS not caused by COVID-19 and ICU survivors from
other causes.8, 9, 10, 11, 12, 13 The term ‘long covid’ is being used to describe
illness in people who have either recovered from COVID-19 but are still reporting
long-term effects of the infection or have had the usual symptoms far longer than
would be expected.
14
Follow-up clinics after hospital discharge are needed to characterise the sequelae
of these patients, and to determine which interventions in the ICU, in the hospital
after ICU discharge, and later in the community may mitigate or treat these sequelae.
Research priorities include a better understanding of the pathophysiology, an evaluation
of ICU and hospital treatments given, and impact of rehabilitation programmes on long-term
outcomes after critical COVID-19. Early rehabilitation
15
or ICU diaries to help reduce post-traumatic stress disorder
16
have been described to mitigate long-term sequalae.
A limitation of the present study is that it included only critically ill patients
admitted to ICUs of hospitals located in northwestern Spain. Thus, the results may
not reflect the experience and results of critically ill COVID-19 survivors of other
ICUs in other regions. Another limitation is that the pre-COVID-19 assessment was
based on patient recall of their quality of life and functional status, and these
could be biased. Regardless, these preliminary results are shared to inform long-term
health-related outcomes of critically COVID-19 patients who needed ICU admission.
These findings may be important for health service planning and for planning the ongoing
support and treatment of survivors of COVID-19 ARDS.