Achim Regenauer presents an overview of the latest long COVID research, and suggests a plausible subgrouping of this multifaceted post-viral condition
In April 2021, I reported on what was known at that point about long COVID, particularly its unknown but potentially long-term duration, lack of a uniform and internationally applied definition, and its complex, diverse set of symptoms, including post-viral fatigue, joint pain and organ-centred manifestations such as impaired lung function (bit.ly/Partner_LongCovid).
A year later, do we have a clearer picture of long COVID and its prognosis? Well, not really. The list of symptoms is now longer, at more than 200. There is still no one clinical case definition, although the WHO’s ICD-10 U09 is a helpful reference (bit.ly/WHO_postCOVID). There are no clear routine laboratory or imaging diagnostics, it has no clear duration, and there is no effective treatment (nor is one in sight). Morbidity trends and life and health insurance underwriting are impacted, but with considerable uncertainty.
More research is key. Unfortunately, many long COVID studies have comprised small cohorts, often only involving special medical aspects and with disappointingly short follow-up times. Interpretation is also hampered by consistency issues, such as metrics at different times after infection, the potential to mistake common symptoms linked to other illnesses for long COVID symptoms, and the lack of definition consensus.
Three recent studies, however, stand out as having enhanced our understanding. These, and the conclusions we can potentially draw from them, have led me to consider that there may be five long COVID ‘subgroups’ (Figure 1 and Figure 2). In addition, with close to half of the COVID-19 patients in these studies (with variation by study) still reporting symptoms after a year, there are obvious and significant consequences for life and health insurers.
A plausible subgrouping
The most reported symptoms of long COVID are clinically unspecific symptoms such as fatigue, malaise, headaches, sleeping difficulties and joint symptoms. These symptoms are subjectively assessed by patients and medical practitioners, rather than picked up in an objective diagnostic test, and they tend to fluctuate over time.
Fatigue and malaise are indicative symptoms of chronic fatigue syndrome (CFS), which is known to have been a post-viral complication or manifestation during previous pandemics and disease outbreaks – for example, in the 1892 flu pandemic (when it was referred to as ‘neurasthenia’ and ‘grippe catalepsy’), the 1918 flu pandemic (‘Parkinsonism’, ‘catatonia’, ‘encephalitis lethargica’) and the SARS-CoV-1 (SARS) outbreak of 2003.
CFS is characterised by a lingering, debilitating fatigue and post-exertional malaise lasting for more than six months, and sometimes for three or more years – 40% of SARS patients, for example, still had CFS symptoms after 3.5 years. One recent study, Nakatomi et al.’s ‘Neuroinflammation in the brain of patients with myalgic encephalomyelitis/chronic fatigue syndrome’, identified chronic low-grade neuroinflammation in CFS patients, which might at some point aid diagnosis. Unfortunately, as is often the case with clinically unspecific symptoms that lack an objective diagnostic test, CFS patients have often been undiagnosed, misdiagnosed or disbelieved. As with long COVID, the syndrome remains poorly understood and poorly investigated.
The overarching term ‘long COVID’ also includes organ-centred manifestations that are clinically specific – in other words, for which objective diagnostic laboratory or functional metrics exist. These include mental, neurological and psychiatric disorders attributed to the central nervous system, and symptoms and findings attributed to other organs, such as the lungs, heart, kidney and liver (Figure 1 and Figure 2).
Relevant here is Taquet et al.’s study ‘6-month neurological psychiatric outcomes in 236 279 survivors of COVID-19, a retrospective cohort study using electronic health records’. This involved US hospitalised and non-hospitalised COVID-19 patients who suffered mild, moderate and severe forms of the disease. It identified a notably higher incidence of mental, neurological and psychiatric disorders among COVID-19 patients six months after infection compared to patients with other acute (non-COVID-19) respiratory tract infections (Figure 3). Incidence was also shown to be positively correlated with age, COVID-19 severity, and prior diagnosis of disorders from this symptom group. A striking 12.8% of the COVID-19 patients developed new or first cases of these symptoms. Considering that such disorders tend to be chronic or recurrent, this could be highly significant for the morbidity claims of disability covers.
It is also possible that mental illness, neurological and psychiatric symptoms affect how these and other long COVID symptoms are experienced and defined by patients; more symptoms and longer recovery periods are conceivable.
Other valuable sources of insight
A comprehensive source of long COVID insights is the UK’s Coronavirus Infection Survey (CIS), which last presented its results on 5 March 2022. Based on self-classification by citizens after a positive COVID-19 infection, the survey indicated that a staggering 2.1 million people (3.8% of the UK population, or around one in 25 people) at a defined point in time were suffering from long COVID. Risk factors included age (35-69 years), gender (female), socio-economic factors (deprived areas), employment sector (health and social care workers) and pre-existing conditions or disabilities.
The main reported symptoms were fatigue (56%), shortness of breath (40%), loss of smell (32%) and difficulty concentrating (31%). In addition, and of relevance to disability covers, 19% reported that their ability to carry out day-to-day activities had been ‘limited a lot’.
Huang et al.’s longitudinal single-centre study from Wuhan, ‘1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study’, sheds light on long COVID’s follow-up at more than one year after infection. A cohort of 1,276 hospitalised adult survivors of COVID-19 (70% having required oxygen, 4% ICU, and with an average age of 59 years) from January-May 2020 (the first COVID-19 cases, which have the longest available data) were followed up at six months and 12 months. The reported symptoms at those times are shown in Table 1. It’s clear that symptoms did not dramatically improve during this time. That 12% were still unable to return to work after 12 months approximately mirrors the CIS findings; this will have a notable impact for insurers, especially for disability covers.
A hint of things to come
Subgrouping long COVID certainly seems plausible. However, we cannot yet draw any definite conclusions, as time is still too short and studies on long COVID remain barely comparable given large variations in definitions, statistical methodologies and endpoints, such as symptoms and findings. Furthermore, this is the first time that an infectious disease has been so intensively investigated in the post-viral phase. It is, however, extremely likely that within the next few years research will uncover new findings about post-viral disease, and that life and health insurance business will be dealing with COVID-19 for many years to come.
PartnerRe continually monitors and maintains a database of all long COVID research studies as a basis for underwriting guidelines, which include questions relating to COVID-19 infection and recovery. It considers that health and disability covers have the highest exposure to long COVID, followed by critical illness, long-term care and death covers.
Opinions expressed are solely those of the author. This article is for general information, education and discussion purposes only. It does not constitute legal or professional advice and does not necessarily reflect, in whole or in part, any corporate position, opinion or view of PartnerRe or its affiliates.
Dr Achim Regenauer is chief medical officer, life and health, PartnerRe