Fatigue and quality-of-life in the year following SARS-Cov2 infection

The “CoronaVirus Disease 2019” pandemic (COVID-19) has been rife across the world for almost 2 years now, with over two hundred million people infected and over four million deaths [1].

Health repercussions were rapidly observed, with a saturation of health systems across almost all countries, and an obvious shortage of beds in healthcare units, which left no other choice but new management for emergencies and critical care provision [2], and finally the instatement of emergency staff reinforcements throughout the world, including France with its “plans blancs” [3].

Infection by Severe Acute Respiratory Syndrome—Coronavirus 2 (SARS-CoV2), the COVID-19 agent appears after a median period of 4 days of incubation, mainly with fever and a cough. In severe cases, this infection triggers acute respiratory distress syndrome (ARDS) and quasi-systemic damage with a wide range of symptoms.

Long-term physical and psychological consequences of this infection are therefore naturally present among patients discharged from hospital following initial hospital stays, often including time in a resuscitation unit. These consequences, which remain largely unknown given the novelty of this pandemic, have been monitored and described in several studies, over a 6-month period post-infection at the most. The main physical symptoms observed have been fatigue or muscular weakness, coupled with respiratory disorders, difficulties sleeping, anxiety, and even depression [4].

Fatigue is a symptom that persists after coronavirus infection, as is the case with certain viral infections, and it forms—with the other afore-mentioned symptoms—the post-viral syndrome [5]. This fatigue quite logically affects the patients’ quality-of-life.

According to the World Health Organisation (WHO), quality-of-life is defined as individuals’ perceptions of their position in life in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standards and concerns. This concept has gained considerable importance over the last 30 years, enabling an improvement in patients’ medical, social and economic care. Some studies have shown that following infection by SARS-CoV2, quality-of-life at 12 weeks and at 6 months was diminished among the patients concerned, as well as among their care providers (family members, friends, etc.) [6, 7].

To our knowledge, only two studies have described the state of health of Covid-19 patients beyond 6 months post-infection; one study focused on global symptoms [8] and the other only analysed the patients’ pulmonary state [9], but neither of them carried out analyses on feelings of fatigue or on quality-of-life at that time.

The objective of our study was therefore to describe the state of health (physical symptoms, including fatigue, and psychological symptoms) of patients who had been hospitalised for SARS-CoV2 infection at 6 and 12 months after onset, with a comparative analysis of quality-of-life and fatigue at these time-points.

Formal diagnoses of SARS-CoV2 infection were made for 479 patients, who were included in the cohort.

After hospitalisation, 128 deaths had occurred. Between hospitalisation discharge and the 6-month assessment 17 deaths had occurred, and there were 16 refusals or individuals lost to follow-up for a total of 318 eligible patients, of whom 193 were excluded (Fig. 1). In all, 120 patients had a follow-up assessment at 6 months and 120 at 12 months.

The initial characteristics of the patients who took part in both follow-up assessments are described in Table 1.

The mean age of the sample was 63.50 years (IQR = [54.00–71.25]) and 54.17% were men. Most patients had symptoms of fever (76.67%), cough (73.33%) and dyspnoea (66.67%). A severe clinical profile, defined as ARDS or severe pneumonia (fever, SpO₂ < 90% respiratory rate > 30/min, acute respiratory failure with respiratory support needed (invasive or non-invasive) or admission in ICU, associated acute circulatory failure (sepsis or septic shock)) was present for 35% of the patients.

Biological data showed a median lymphocyte count at 0.9 G/L (IQR [0.6–1.2]), a median neutrophil count at 5.1 G/L (IQR [3.3–6.7]) and a median CRP of 92.00 mg/L (IQR [34.38–157.25]).

Concerning evolution, 43.33% required oxygen therapy and 29.17% were transferred to the resuscitation unit. Antibiotic therapy was used for 95.83% of the patients, 92.5% of the patients received anti-coagulants and 66.6% received corticoid therapy.

At 6 months and 12 months, about 40% of the patients presented dyspnoea. The median mMRC score (at the two assessment) was 1 (IQR = [0–2]) and there was no significant difference between M6 and M12 (p value = 0.454).

The symptoms following the infection persisted at M6 and M12, with about 20% of the patients with cough and headache. Other symptoms were also observed (Table 2), anxiety, and problems with concentration and memory in particular.

More than half of the patients at 6 and 12 months reported asthenia; the FSS fatigue scale was administered at both assessments, with a median of 3.11 (IQR [1.73–5.00]) at M6 and 3.22 (IQR [1.89–4.95]) at M12. Applying the threshold of the mean score calculated in the population, it was observed that 35% and 44% of the patients were experiencing fatigue at M6 and M12, respectively. The level of fatigue did not seem to differ between the two assessments (p value = 0.41), despite the tendency to increase.

Concerning quality of life, the SF12 was administered at M6 and M12, with a mean PCS12 score at 6 months of 42.85 (95% confidence interval (95% CI [41.05–44.65]) and a mean MCS12 score of 46.70 ((95% CI) [45.34–48.06]). There was no difference at M6 and M12 between the two SF12 scores: PCS12 and MCS12 with a p value of 0.417 and 0.501 respectively, although a slight improvement in the scores was observed at M12. Detailed results by SF12 components of patients assessed at M6 and at M12 were presented in Additional file 1: Table S1.

We found no differences between the results of scores taken by patients (SF12, FSS and mMRC) who presented a severe initial respiratory status versus those with a non-severe respiratory status. All p-values were greater than 0.05 (Table 3).

Finally, we compared the mean SF12 scores with those in the general population in France (Fig. 2) [19]. The general population was composed of 48% of males and the mean age (SD) was 44.6 (18.1) years [20]. We observed lower scores among Covid-19 patients than in the general population, meaning that quality-of-life in both the physical and the psychological dimensions was poorer (p value < 0.001 for the PCS12 at M6 and M12 versus the norm, and p value 0.025 and 0.037 respectively for the MCS12 assessed at M6 and M12, versus the norm) [19].

To our knowledge, this study was one of the first to describe the health state of Covid-19 patients at 6 and 12 months including assessments of quality-of-life and persistent fatigue. It highlighted persistent dyspnoea, with an mMRC score above 1 for more than half of the patients. The FSS score also evidenced persistent fatigue for 35% of the patients at M6 and 43% at M12. The two SF12 scores, PCS12 and MCS12, evidenced physical and mental quality-of-life scores below the mean for the French population. For all these scores, no difference was observed between the two time-points. This could therefore suggest the long-term persistence of certain symptoms, with general fatigue and poorer quality-of-life than the norm, both physical and mental.

Certain studies have described and compared patients’ state of health at 6 months after hospital discharge [4] and others at 6 and 12 months [8, 21, 22]; all these studies have reported the presence of fatigue and a change in quality-of-life among patients after hospital discharge. Only one study used a quality-of-life assessment (HRQoL) [8], but none used the FSS score or the SF12 score. However, the results from all these studies and from ours concur on the fact that the main symptoms present after infection by SARS-CoV2 were fatigue, dyspnoea, anxiety and repercussions on cognitive functions [8, 21, 22]. In our study, we focused particularly on the patients’ clinical state, using the SF12 score to determine global quality-of-life. Our results mainly suggest stability in their clinical state between the two time-points (M6 and M12), thus pointing to a period of latency between the end of the infection and a return to what is considered a normal life. Our study was conducted early on and did not have the privilege nor the objective to determine the effect of vaccination on quality of life since the patients were not all vaccinated at assessment. Our population was older and included more men than the population used for comparison.

This study thus showed a non-negligible decrease in the patients’ physical and mental quality-of-life at 6 months and 1 year following infection by SARS-CoV2, compared to the French general population. It showed persistence, 1 year after the initial infection, of fatigue and dyspnoea, alongside the appearance of psycho-neurological symptoms.

These observations raise several issues, in particular that concerning the evolution of the disease and the “post-COVID” period. They are also in favour of the “Long Covid” hypothesis. This condition was defined by the French health authorities [23] as confirmed SARS-CoV2 infection with the initial symptoms persisting beyond 4 weeks after the onset of the acute phase, and not explained by another diagnosis.

While it is easy to incorporate fatigue into the notion of “Long Covid”, the fatigue and the decrease on quality-of-life observed could also be explained by a psychiatric dimension [24]. Indeed, certain studies have found possible neuro-psychiatric effects, or even an aggravation of certain psychiatric pathologies that were already present, following infection with SARS-CoV2, as with other already known viral infections [24, 25].

This overlap between infection by SARS-CoV2 and a probable cerebral inflammation could explain in part feelings of ill being or chronic fatigue. Perceived quality of life could thus be affected despite a satisfactory physical state in clinical consultation.

These hypotheses should be explored and assessed for COVID-19, but they can already explain the decline in quality-of-life, especially for the psychological sphere, observed among patients, sometimes discordant with the physical state [24].

We were able to maintain the same number of patients between the two time-points. All the scales and tools used to assess fatigue and quality-of-life were standardised and validated. The researchers were experienced specialist doctors, which enabled reliable data collection. Furthermore, the patients were seen at 6 and 12 months by the same researchers, enabling comparable data collection between the two assessments.

This study was one of the first descriptions of the state of health of COVID-19 patients with certain persistent symptoms: fatigue and deterioration in physical and mental quality-of-life. This information could guide care providers in the follow-up care provided to patients and in rehabilitation, and if needed, in neuro-psychiatric care.