Long-term characteristics of long-COVID following hospitalization

As of December 2021, approximately 271 million instances of SARS-CoV-2 have been documented worldwide, with 11 million cases in the United Kingdom and over half a million patients admitted to hospitals in the United Kingdom with COVID-19. It has been determined that this large population is at significant risk of continuing health problems six months after discharge. Such health problems are associated with decreased physical function and health-related quality of life.

To identify ongoing healthcare needs and the required response by healthcare systems and policymakers for this already huge and ever-increasing population, it is critical to determine the longer-term trajectory of recovery.

Study: Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study. Image Credit: Starocean/ShutterstockStudy: Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study. Image Credit: Starocean/Shutterstock

The processes that are driving long-term symptom persistence are unknown at this time. One theory is that the acute COVID-19-induced hyper-inflammation leads to a long-term inflammatory state, which is associated with dysregulated immunity and multiorgan failure. Although several researchers have linked higher inflammatory markers, such as interleukin-6 (IL-6), to the severity of acute sickness, no significant studies have investigated the link between systemic inflammation and long-term health problems following COVID-19.

A team of researchers  used the ongoing PHOSP-COVID longitudinal study cohort to determine patient-perceived recovery, the associated risk factors for failure to recover one year after discharge, and to investigate the association between the previously described clusters and multiple inflammatory mediators using a proteomics panel in this report. The authors present the one-year recovery trajectory for various health domains, as well as the variances in recovery trajectory by cluster.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* server.

The study

At five months after discharge, 25.5% of patients felt fully recovered, and at one year, 28.9%, with similar proportions reported in those with matched data. The adjusted proportion of participants feeling entirely recovered at one year is 212/1063 or 604/1063, respectively, assuming all participants who had missing data at one year had either not recovered or fully recovered.

The previously identified four clusters representing very severe' physical and mental health impairment (n=319),' severe' physical and mental health impairment (n=493), 'moderate' physical health impairment with cognitive impairment (n=179), and ‘mild’ mental and physical health impairment (n=645) were confirmed for the current five-month dataset with complete data n=1636. In the previous trial, 86.7 % (664/766) of participants were reassigned to the same recovery cluster as before; the cognitive cluster had the highest assignment changes (60/127). In comparison to the 'mild' cluster (177/624, 28.4 %) and (288/568, 50.2 %), the extremely severe cluster had a larger proportion of female sex (165/306, 53.9 %) and obesity (204/288, 70.8 %).

At one year after discharge, the top ten most common persistent symptoms were fatigue (463/770, 601 %), aching muscles (442/809, 546 %), physical slowing down (429/811, 529 %), poor sleep (402/769, 523 %), breathlessness (395/769, 514 %), joint pain or swelling (382/803, 476 %), slowing in thinking (377/808, 467 %), pain (359/770, 466 %), and short-term memory loss.  Overall, the prevalence of these conditions remained essentially unchanged from five months to one year, with small reductions in rates of limb weakness (476 % at five months vs. 417 % at one year, p=0.010), paraesthesia (406 % vs. 352 %, p=0014), and balance problems (349 % vs. 300, p=0008). When compared to five months after discharge, there was either no or minimal improvement in patient-reported outcome measures (PROMS), physical function, cognitive impairment, or organ function at one year.

At one year, 147/684 (215%), 169/680 (249%), and 68/680 (100%), respectively, had clinically relevant anxiety and/or depression symptoms, 68/680 (100%), exhibited symptoms consistent with post-traumatic stress disorder, and 55/623 (88%), had severe cognitive impairment. At five months and one year, those who felt totally recovered, not sure, or not entirely recovered had significantly different symptoms and physical function, although cognitive impairment and markers of organ function (except for Forced Vital Capacity [FVC]) did not. Similarly, participants who reported having fully recovered, not sure, or not recovered at five months and one year had a significantly different health-related quality of life.

Between five months and one year, symptoms of anxiety, depression, dyspnea, and exhaustion improved dramatically in the very severe cluster, but there was little change in physical performance and no general change in systemic inflammation as indicated by CRP levels. The intermediate cognitive cluster showed a substantial improvement after a year, while the severe cluster showed a non-significant tendency toward improvement, but the other clusters remained unaltered. Decrements in health-related quality of life (EQ5D-5L), disability (WG-SS-SCo), and severity of dyspnea and fatigue experienced in the previous 24 hours were seen at five months and sustained at one year when compared to patient perceptions of their health prior to COVID-19.


This study demonstrates the urgent need for healthcare services to support this huge and quickly growing patient population, which has a significant burden of symptoms, lower exercise ability, and significant reductions in health-related quality of life after one year. Long-COVID has the potential to become a highly prevalent new long-term illness if effective treatments are not found. This research also lays the groundwork for researching Long-COVID treatments using a precision medicine approach to target treatments to the relevant phenotype, as well as anti-inflammatories, weight loss, and rehabilitation to improve health-related quality of life.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Colin Lightfoot

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.


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