The presence of multimorbidity and polypharmacy is associated with a 77% higher risk of a positive COVID-19 test

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The presence of two or more long term health conditions – known as multimorbidity – is linked to a 48% higher risk of a positive COVID-19 test.

While it is well recognized that the risk of a severe COVID-19 infection is linked to certain long-term health conditions, little is known, so far, about the effects of multimorbidity and polypharmacy (taking multiple medications) on the risk of a serious coronavirus infection.

Now, a new study led by the University of Glasgow and published today in PLOS ONE, is the first to link both multimorbidity and polypharmacy with the risk of having a positive COVID-19 test.

This association was particularly apparent for those with two or more cardiometabolic health conditions such as diabetes and high blood pressure. Researchers found that the presence of two or more such conditions was associated with a 77% higher risk of a positive COVID-19 test.

Those of non-white ethnicity, who also had multimorbidity, had almost three times the risk of a positive COVID-19 test.

Overall, people with multimorbidity who appeared to have the highest risk of COVID-19 infection were from socioeconomically deprived areas, of non-white ethnicity, considered severely obese, and those with reduced renal function.

The researchers believe their findings will have implications for clinical and public health decision making as the SARS-CoV-2 pandemic continues around the world.

Dr. Barbara Nicholl, from the University of Glasgow who led the study, said: “Multimorbidity and polypharmacy are global healthcare challenges in their own right.

Our study shows that having a positive COVID-19 test is more common in those living with these health conditions.

These results will be important for public health and clinical decisions in the future as we continue to manage the health of those at greatest risk of a severe COVID-19 infection during this pandemic.”

Professor Frances Mair, the University of Glasgow Norie Miller Professor of General Practice and leading expert on multimorbidity, said: “Given the high prevalence of multimorbidity, particularly in older age groups, the more detailed understanding of the associations between these complex health needs and COVID-19, as provided in this study, will improve our understanding of the risks and help us better advise those most vulnerable to severe infection.”

The study is based on UK Biobank data, which is now linked to COVID-19 test results, and included 428,199 adults aged 37-73 at the time of recruitment (2006-2010) across England and Wales.

The study, “Multimorbidity, Polypharmacy, and COVID-19 infection within the UK Biobank Cohort,” is published in PLOS ONE.


Direct risks to older adults

The most obvious risks to older adults during the pandemic emerge from the relationship between the agent, host and environment – between the virus, the health status of the older adult and the pathophysiological response to the infection.

Morbidity

Older adults are more likely to develop a symptomatic rather than an asymptomatic infection. Of those who develop a symptomatic infection – older adults are further, more likely to develop a moderate to severe infection than a mild infection.

The percentage of infected individuals requiring hospitalization appears to rise sharply over the age of 50 years, Data based on cases reported from China noted that hospitalization was required in 4.25% of cases detected between 40 and 49 years, 8.16% between 50 and 59 years, 11.8 % between 60 and 69 years, 16.6% between 70 and 79 years and 18.4% above 80 years of age (Verity et al., 2020).

A comparison study in china found that older adults are more likely than young and middle aged adults to have a Pneumonia Severity Index (PSI) of IV or V (indicating severe infection). They were more likely to have multiple lobar involvement on CT scan, have a lower percentage of lymphocytes in their differential count and higher C reactive protein (CRP) levels.

They also appeared more likely to develop acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), require invasive mechanical ventilatory support and respond more rapidly to interferon therapy – though these differences did not reach statistical significance (Liu et al., 2020).

The risk for infection and disease is linked to impaired presentation of antigen by the NK lymphocytes to T and B lymphocytes due to the decline in immunocompetency with age. This is associated with an increased cytokine response to the infection – causing a widespread inflammatory response which leads to multi-organ dysfunction and respiratory failure (Adhikari et al., 2020).

Mortality
An approach to modelling the severity of infection due to the novel (SARS-CoV-2) coronavirus (based on data from China) published in the Lancet estimated a case fatality ratio of 4.5 % in people over 60 years of age, compared to 1.4 % in people below 60 years of age.

The case fatality ratio was the highest in those aged above 80 years – 13.4% of all cases detected (Verity et al., 2020).

This increased vulnerability of older adults has contributed to higher case and mortality rates in countries undergoing population ageing. In a statement by the WHO Regional Director, Europe, it was noted that 29 of the 30 with the largest proportion of older adults were member states of Europe (except Japan).

95% of the deaths in these countries occurred in adults over 60 years of age and 50 % of deaths in those over 60 years of age (WHO Europe Statement on Older Adults in COVID-19, 2020).

In India, 51.2 % of the mortality due to COVID-19 has been in people over 60 years of age, as reported by the Government of India on April 30, 2020 (Diwanji, 2020). The risk for severe infection and mortality appear to be linked to stochastic age (reflecting underlying oxidative stress and epigenetic changes) rather than chronological age.

Thus, frailty and mobility appear to mediate the relationship between infection and an adverse health outcome (Begely, 2020)

Comorbidities
Among those infected, patients with co-morbidities are more likely to develop severe infection and mortality than those without co-morbidities (Guan et al., 2020)

Multi-morbidity increases with age. An epidemiological study in Scotland reported two or more chronic health conditions in 30.4% of adults between 45 and 64 years, 64.9% between 65 and 84 years and 80% above 85 years of age (Divo et al., 2014).

Of cases reported from China, 25.1% of patients reported at least one co-morbid medical illness and 9.2% reported having two or more co-morbid medical illnesses.

The mean age of patients with at least one co-morbidity was 60.8 years and with those with two or more co-morbidities was 66.2 years compared to the mean age of 48.9 years in the study population. Both groups had a poorer prognosis than those without co-morbidities with a hazard ratio of 1.79 and 2.59, respectively (Giacomo et al., 2020).

Adverse drug events
Older adults are also more prone to adverse drug events as a consequence of exposure to pharmacotherapeutic agents used in the treatment of the novel coronavirus.

This is partly due to pharmacokinetics with age leading to an increased drug half-life and reduced plasma clearance rates (Sun et al., 2020). This risk is unclear (though non-negligible) and extend to several off label therapies which are under study including – chloroquine/hydroxychloroquine, lopinavir/ritonavir, amantadine, interferon and plasma therapy.

A trial of chloroquine in Brazil has been halted prematurely due to concerns about cardiotoxicity (Borba et al., 2020). Reported adverse drug effects in cases with off label therapies include – cardiotoxicity (including QTc prolongation and arrhythmia), renal, hepatic, visual and hearing impairment; and dermatitis (Dimitrova, 2020).

Open labelled studies also document the increased possibility of drug-drug interactions and cumulative toxicity, as seen with the concurrent administration of lopinavir and azithromycin (Singh et al., 2020).

*-*- reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397988/


More information: Ross McQueenie et al. Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort, PLOS ONE (2020). DOI: 10.1371/journal.pone.0238091

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