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COVID-19’s dangerous legacy

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After the symptoms fade, COVID-19’s effects linger After the symptoms fade, COVID-19’s effects linger on

When COVID-19 appeared on a poorly prepared world stage, healthcare professionals (HCPs) focused on saving lives and preventing infection. But COVID-19’s direct and indirect clinical effects will probably persist long after the curtain falls on this pandemic.

It’s already clear that COVID-19’s effects can linger long after the acute symptoms resolve. A study of 143 patients reported that only 13% were symptom-free a mean of 60.3 days after the onset of COVID-19. Thirty-two per cent had oneto two symptoms, 55% at least three symptoms and 44% reported a worse quality of life. None of the patients still had fever or other symptoms of acute infection. The most common persistent symptoms were fatigue (53%), dyspnoea (43%), joint pain, (27%) and chest pain (22%).1

In some cases, chest pain may raise a suspicion of COVID-19–related heart damage. Between 20% and 30% of patients admitted to hospital with COVID-19 showed raised levels of troponin, a group of proteins that help cardiac and skeletal muscle contract. An injury, such as a heart attack, to the myocardium releases troponin into the blood.2

Moreover, in a study of 100 patients who recovered from COVID-19, magnetic resonance imaging revealed persistent cardiac involvement in 78% and on-going myocardial inflammation in 60%. These changes were independent of pre-existing conditions, the severity of COVID-19, the overall course of the acute illness and the time from the original diagnosis. Most patients recovered at home. But the extent and severity of the cardiac inflammation was similar to that among hospitalised patients.3 Cardiologists are concerned that the heart damage could increase the risk of long-term cardiovascular complications, such as atrial fibrillation and other arrythmias, coronary artery disease and death.2 So, on-going investigations of the long-term cardiovascular consequences of COVID-19 are essential.2,3

On the other hand, some outcomes may improve. A study of controller inhalers used by 7578 patients (77% asthma) reported that mean daily adherence rose by 14.5% (from 53.7% to 61.5%) between the first seven days of January 2020 to the last seven days of March 2020. During the last week of March, about 53% of patients showed at least 75% adherence, a 14.9% increase from the first week of January.4 In theory at least, this improved compliance should enhance outcomes in people with asthma or chronic obstructive pulmonary disease. Whether adherence will remain higher after the initial fears around COVID-19 subside remains one of the many moot points around the pandemic’s clinical legacy.

The effect on the brain

The COVID-19 pandemic and the social isolation seems to have triggered mental health problems, such as increased stress, anxiety, depression and post-traumatic stress disorder among the public and, not surprisingly, patients, family members and healthcare professionals.5,6 If previous pandemics and epidemics are anything to go by, some of the distress from the pandemic may herald longer-term mental health problems for some people.5

Moreover, in about 36% of patients, COVID-19 causes neurological symptoms, such as dizziness, headache, impaired consciousness and seizures. In about 25% of these patients, SARS-CoV-2 directly involved the central nervous system. At discharge, about a third of people show cognitive impairment or motor deficits.7 A recent paper raises concerns about COVID-19’s long-term neurological consequences.7

People with severe COVID-19 show high levels of proinflammatory cytokines (chemicals that carry messages between cells). This ‘cytokine storm’ can cause acute respiratory dysfunction and may accelerate or exacerbate cognitive decline. In theory, the changes may, the paper warns, increase the risk of developing neurological conditions, particularly Alzheimer’s disease.7 It’s worth remembering that many people who develop severe COVID-19 are older and may, therefore, be particularly susceptible to the virus’s cognitive effects. But, once again, only time will tell.

COVID-19 has left parts of the economy reeling. Based on previous experience – such as the Asian Financial crisis, the ‘Great Recession’ that began in 2007, the economic problems following the collapse of the Soviet Union and the Great Depression of the 1930s – suicide rates may rise unless the economy recovers rapidly. A review found that 31 of the 38 studies examined confirmed an association between economic recessions and increased suicide rates. Two reports found the opposite. The remainder either failed to find an association or were inconclusive.8

The indirect effects

COVID-19’s impact on health as well as medical and social services will almost certainly increase mortality and mortality from other conditions. For instance, at the time of writing the number of COVID-19 cases is rising in sub-Saharan Africa, which could easily overwhelm local health services, force social isolation and hinder attempts to tackle malaria.9 Some 3.2 billion people live in areas – mainly in Africa, South America and South-East Asia – where malaria is endemic. During 2018, 228 million cases of malaria occurred worldwide, which killed 405,000 people.10

Severe disruption to malaria prevention activities could more than double deaths from the parasite in 2020 compared with 2019, a recent paper warns. For example, not deploying long-lasting insecticidal nets and halving case management for 6 months could mean mortality from malaria rise to 779,000 deaths over 12 months in sub-Saharan Africa alone. Increased poverty, malnutrition and social insecurity means that this may underestimate the full impact.9

Again, the effects of an increase in malaria in the wake of COVID-19 could persist for years. Many people who survive cerebral malaria experience, for example, cognitive impairment, behavioural disorders and neurological deficits.11 Following cerebral malaria, children can endure developmental and chronic impairments in cognition and executive functioning affecting, for example, speech, language, memory and learning.12 Even mild malaria can cause psychiatric symptoms – such as confusion, intermittent psychosis, delirium, anxiety and depression – which can linger long after the acute symptoms resolve.12

Meanwhile, diagnostic delays because of the pandemic could translate into ‘substantial increases in the number of avoidable cancer deaths in England’.13,14 During lockdown, fewer people sought health care and diagnostic services were suspended or operated at reduced capacity. In April 2020, for example, the NHS performed 90% fewer endoscopies than in each of the first three months of 2020.13 Cancer Research UK suggested in July that compared with 2019, 51% more people are waiting for colonoscopies, 46% more for flexi-sigmoidoscopies (both detect bowel malignancies), 44% more for gastroscopies (oesophageal and stomach cancer) and 23% more for cystoscopies (bladder cancer).15

Diagnostic delays mean that, depending on the model’s assumptions, breast cancer deaths could increase by 7.9% to 9.6% within 5 years of diagnosis compared with pre-pandemic mortality (281–344 additional deaths). Deaths from lung cancer could increase by an estimated 4.8–5.3% (1235–1372 additional deaths), colorectal cancer by 15.3–16.6% (1445–1563 additional deaths) and oesophageal cancer by 5.8–6.0% (330-342 additional deaths). So, COVID-19 could result in 3291–3621 additional deaths within 5 years from these cancers alone.13

Another model examined the impact of delayed treatment on excess mortality from 20 common cancers. In England, the 2-week-wait pathway diagnosed, on average, 6281 patients with stage I–III cancer each month between 2013 and 2016. An estimated 27% of these patients would die within 10 years from cancer. A 3-month lockdown during which 25% and 75% of symptomatic patients delayed their presentation will translate into an estimated 181 and 542 additional deaths respectively. The ‘estimates suggest that, for many cancers, delays to treatment of 2–6 months will lead to a substantial proportion of patients with early stage tumours progressing from having curable to incurable disease’.16 Cancer Research UK told IN that nurses should ‘urge people with any persistent, worsening or unexplained symptoms to get them checked out by their doctor’.

We won’t know lockdown’s impact on cancer deaths and morbidity for many years. For example, a delayed breast cancer diagnosis may mean that cure needs mastectomy rather than lumpectomy. In general, 10-year survival is synonymous with cure, which reflects the ability of surgery or radical radiotherapy to restore normal or near-normal life expectancy.16 So, the excess deaths caused by the disruption to cancer pathways will not be fully clear for at least a decade.16

Indeed, we’re still in the early acts of the pandemic and much of the future course remains unknown or at least uncertain. But one thing’s clear: it will be many years before we fully appreciate the pandemic’s full impact on the world’s health.


Mark Greener is a freelance medical writer and journalist

References

1. Carfì A, Bernabei R, Landi F, Group ftGAC-P-ACS. (2020) Persistent symptoms in patients after acute COVID-19. JAMA. 324(6):603-5. https://doi.org.10.1001/jama.2020.12603

2. Mitrani RD, Dabas N, Goldberger JJ. (2020) COVID-19 cardiac injury: Implications for long-term surveillance and outcomes in survivors. Heart Rhythm. https://doi.org.10.1016/j.hrthm.2020.06.026

3. Puntmann VO, Carerj ML, Wieters I, et al. (2020) Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiology. https://doi.org.10.1001/jamacardio.2020.3557

4. Kaye L, Theye B, Smeenk I, Gondalia R, Barrett MA, Stempel DA. (2020) Changes in medication adherence among patients with asthma and COPD during the COVID-19 pandemic. The Journal of Allergy and Clinical Immunology: In Practice. 8(7):2384-5. https://doi.org.https://doi.org/10.1016/j.jaip.202...

5. Xiao S, Luo D, Xiao Y. (2020) Survivors of COVID-19 are at high risk of posttraumatic stress disorder. Global Health Research and Policy. 5:29. https://doi.org.10.1186/s41256-020-00155-2

6. Serafini G, Parmigiani B, Amerio A, Aguglia A, Sher L, Amore M. (2020) The psychological impact of COVID-19 on the mental health in the general population. QJM. https://doi.org.10.1093/qjmed/hcaa201

7. Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. (2020) Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer’s Research & Therapy. 12(1):69. https://doi.org.10.1186/s13195-020-00640-3

8. Oyesanya M, Lopez-Morinigo J, Dutta R. (2015) Systematic review of suicide in economic recession. World Journal of Psychiatry. 5(2):243-54. https://doi.org.10.5498/wjp.v5.i2.243

9. Sherrard-Smith E, Hogan AB, Hamlet A, et al. (2020) The potential public health consequences of COVID-19 on malaria in Africa. Nature Medicine. https://doi.org.10.1038/s41591-020-1025-y

10. Greener M. (2020) Defeating malaria: new weapons against one of our deadliest foes. Prescriber. 31(July/ August):18-22.

11. Carpio A, Romo ML, Parkhouse RME, Short B, Dua T. (2016) Parasitic diseases of the central nervous system: Lessons for clinicians and policy makers. Expert Review of Neurotherapeutics. 16(4):401-14. https://doi.org.10.1586/14737175.2016.1155454

12. Nevin RL, Croft AM. (2016) Psychiatric effects of malaria and anti-malarial drugs: Historical and modern perspectives. Malaria Journal. 15(1):332. https://doi.org.10.1186/s12936-016-1391-6

13. Maringe C, Spicer J, Morris M, et al. (2020) The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: A national, population-based, modelling study. The Lancet Oncology. 21(8):1023-34. https://doi.org.10.1016/S1470-2045(20)30388-0

14. Hamilton W. (2020) Cancer diagnostic delay in the COVID-19 era: What happens next? The Lancet Oncology. 21(8):1000-2. https://doi.org.10.1016/S1470-2045(20)30391-0

15. Cancer Research UK. (2020) 44% rise in patients waiting for tests to diagnose bowel, stomach, bladder and oesophageal cancer Available at www.cancerresearchuk.org/about-us/cancer-news/press-release/2020-07-20-44-rise-in-patients-waiting-for-tests-to-diagnose-bowel-stomach-bladder-and-oesophageal-cancer-0.

16. Sud A, Torr B, Jones ME, et al. (2020) Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: A modelling study. The Lancet Oncology. 21(8):1035-44. https://doi.org.10.1016/S1470-2045(20)30392-2

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