Dr. Achim Regenauer, our Chief Medical Officer, presents an overview of what some of the latest long Covid research is indicating, adding his own perspective on a plausible subgrouping of this multifaceted, post-viral condition.
Back in April 2021, I reported on what was known at that point about long Covid1, in particular its unknown but potentially long-term duration, lack of a uniform, internationally applied definition, and its complex, diverse set of symptoms, including post-viral fatigue, joint pain and organ-centered manifestations, such as impaired lung function.
Well no, not really. The list of long Covid symptoms is now longer (at over 200), there is still no one clinical case definition (although the WHO’s ICD-10 U09 is a helpful reference2), no clear routine laboratory or imaging diagnostics, no clear duration, and no effective treatment (nor is one in sight). Morbidity trends and Life & 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, and the lack of definition consensus.
Three recent studies, however, stand out to me as having enhanced our understanding. It’s these, and the conclusions we can potentially draw from them, that have led me to consider that there are possibly five long Covid subgroups; see figure 1. 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 & Health insurers. I will concentrate on these particular studies and my considerations in this short paper.
Figure 1: Schematic of a working hypothesis by the author to reflect the comprehensive and complex nature of long Covid’s > 200 symptoms. It seems plausible to the author that what is currently considered to be long Covid, can in fact be broken down into five subgroups. The size of the bubbles mirrors the approximate relative incidence of each subgroup. See figure 2 for the most frequently occurring symptoms in each subgroup and impacted Life insurance covers. Source: PartnerRe.
The most commonly reported symptoms of long Covid are clinically unspecific symptoms – fatigue, malaise, headaches, sleeping difficulties and joint symptoms dominate – these symptoms are subjectively (rather than via an objective diagnostic test) assessed by patients and medical practitioners, and tend to fluctuate over time.
Fatigue and malaise are indicative symptoms of chronic fatigue syndrome (CFS), which is known as a post-viral complication/manifestation from previous pandemics and disease outbreaks; for example, from the 1892 flu pandemic (“neurasthenia”, “grippe catalepsy”3), the 1918 flu pandemic (“parkinsonism”, “catatonia”, “encephalitis lethargica”4) and the SARS-CoV-1 (SARS) outbreak of 2003.
CFS is characterized by a lingering, debilitating fatigue and post-exertional malaise lasting for over 6 months, and sometimes for 3 or more years5; 40% of SARS patients, for example, still had CFS symptoms after 3.5 years6. One recent study7 identified chronic, low-grade neuroinflammation in CFS patients, which might at some point aid diagnosis. Unfortunately, however, as is often the case with clinically unspecific symptoms lacking an objective, diagnostic test, CFS patients have been mostly undiagnosed, misdiagnosed or disbelieved over time. As with long Covid, CFS remains poorly understood and poorly investigated.
Figure 2: A working hypothesis by the author to reflect the comprehensive and complex nature of long Covid’s > 200 symptoms. It seems plausible to the author that what is currently considered to be long Covid, can in fact be broken down into five subgroups (see figure 1 for a schematic of the approximate relative incidences (mirrored by the bubble sizes) and possible subgroup interaction). For each subgroup, the most frequently occurring symptoms are listed, together with the impacted Life insurance covers; Disability (DI), Life and Critical Illness (CI). Source: PartnerRe.
The overarching term of long Covid also includes clinically specific (i.e., objective diagnostic laboratory or functional metrics exist) organ-centered manifestations: 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 (see figures 1 and 2).
A relevant example study to present here is a large retrospective cohort study8 that involved 236,379 US hospitalized and non-hospitalized COVID-19 patients (mild, moderate and severe forms). This study identified a notably higher incidence of mental, neurological and psychiatric disorders amongst the COVID-19 patients at 6 months after infection compared to patients with other acute (non-Covid) illnesses; see figure 3. Incidence was also shown to be positively correlated with age, COVID-19 severity and prior diagnosis of disorders from this symptom group. Of considerable concern, a striking 12.8% of the COVID-19 patients developed new/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.
Figure 3: Retrospective cohort study involving 236,379 US hospitalized and non-hospitalized COVID-19 patients (all severities). The graphs show how the incidence of mental, neurological and psychiatric disorders in the COVID-19 patients exceeds that of the comparison (non-Covid) patient cohorts. Source: Taquet, M. et al (2021)8.
There is also the potential that having mental illness, neurological and psychiatric symptoms impacts on how these and other long Covid symptoms are experienced and defined by patients; more symptoms and longer recovery periods are conceivable.
A comprehensive source of long Covid insights is the UK’s Coronavirus Infection Survey (CIS), which (at the time of writing) last presented its results on October 7, 2021. Based on self-classification by citizens after a positive COVID-19 infection9, the survey indicated that a staggering 1.1 million people (1.7% of the UK population) 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 preexisting conditions/disabilities.
The main reported symptoms are fatigue (56%), shortness of breath (40%), loss of smell (32%) and difficulty concentrating (31%).
In addition, and of particular relevance to Disability covers, 19% reported that their ability to carry out day-to-day activities had been “limited a lot”.
A longitudinal single-center study from Wuhan10 sheds first light on long Covid’s follow-up at more than one year after infection11. A cohort of 1,276 hospitalized adult survivors of COVID-19 (70% having required oxygen, 4% ICU, average age 59 years) from January-May 2020 (i.e., first Covid cases, therefore having the longest available data) were followed up at 6 months and 12 months. The reported symptoms at those times are shown in table 1. It’s clear that symptoms did not dramatically improve over 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.
Table 1: Extract of study results of patients reporting symptoms at 6 and 12 months after SARS-CoV-2 infection. The percentages do not change much over this time, indicating the long-haul nature of long Covid. Source: Lixue Huang, MD et al (2021)10.
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 for many years to come.
At PartnerRe, we continuously monitor and maintain a database of all long Covid research studies as a basis for our underwriting guidelines, which include questions relating to COVID-19 infection and recovery. We consider that Health and Disability covers have the highest exposure to long Covid, followed by Critical Illness, Long-term Care, and Death covers.
If you would like to discuss this topic with the author or with your PartnerRe contact, please get in touch, we would be delighted to talk to you.
Dr. Achim Regenauer, Chief Medical Officer, Life & Health
Editor: Dr. Sara Thomas, PartnerRe
2 “COVID-19 condition occurs in individuals with a history of probable or confirmed SARSCoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.” World Health Organization, A clinical case definition of post COVID-19 condition by a Delphi consensus, October 6, 2021 https://apps.who.int/iris/bitstream/handle/10665/345824/WHO-2019-nCoV-Post-COVID-19-condition-Clinical-case-definition-2021.1-eng.pdf
8 Taquet, M. et al (2021) https://www.thelancet.com/action/showPdf?pii=S2215-0366%2821%2900084-5
9 71% had COVID-19 at least 12 weeks prior to the self-classification; 35% had COVID-19 at least one year prior to the self-classification.
10 Lixue Huang, MD et al (2021) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01755-4/fulltext
11 Although this can’t be generalized to non-hospitalized patients or younger persons.