A long journey ahead with COVID-19

The long-term effects of COVID-19 in low-risk individuals need to be studied urgently

A long journey  ahead with COVID-19

Almost 70% of young, low-risk individuals in a COVID-19 study had one or multiple organ impairment after four months of the infection. Such data has implications not only for the burden of the so-called ‘long COVID’, but also on our overall approach towards managing this disease among younger segments of the population. Initial research and clinical data around SARS-CoV-2 induced organ damage was predominantly focused on the respiratory system. Indirect effects on other organs, such as aggravation of cardiovascular diseases, immune dysregulation and cancers were also observed.

COVID-19 involves a convergence of infectious disease with under-treated non-communicable diseases and other social determinants of health. It has been established that pre-existing non-communicable diseases and other risk factors are important predictors of poor COVID-19 outcomes. However, the majority of research so far has focused on acute-phase infections in hospitalized patients and on patients who have died from COVID-19. There is an urgent need to have studies regarding long COVID in low-risk individuals who constitute almost 80% of the population. Many government policies have emphasized the excess risk of mortality in high-risk conditions. However, as the pandemic progresses, it is assumed that COVID infections among younger individuals without underlying conditions pose few risks, even though there is no concrete proof or knowledge of chronic pulmonary and extrapulmonary effects.

Assessing multi-organ damage

Dennis A et al assessed multi-organ burden after COVID infections with patient-reported, validated questionnaires, fasting blood investigations and multi-organ MRI. Questionnaires on quality of life, mobility, self-care, usual activity, pain, anxiety and breathlessness were accompanied by tests for full blood count, serum biochemistry (sodium chloride, bicarbonate, urea, creatinine, bilirubin, alkaline phosphatase, aspartate transferase, alanine transferase, lactate dehydrogenase, creatinine kinase, gamma-glutamyl transpeptidase, total protein, albumin, globulin, calcium, magnesium, phosphate, uric acid, fasting triglycerides, cholesterol (HDL, LDL), iron, iron-binding capacity both unsaturated and total, inflammatory markers like high sensitivity C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). The multi-organ MRI included lungs, heart, liver, pancreas, kidneys and spleen. These scans of patients were compared with established reference ranges to determine impairment for each organ. The majority of patients reported continued to have cardiorespiratory (92%) and gastrointestinal (73%) problems, fatigue (98%), muscle aches (88%) and shortness of breath (87%). 99% of patients had four or more problems and 42% had ten or more symptoms impairing 52% of them in moderate problems in undertaking usual activities. The biochemical parameters such as triglycerides, cholesterol, LDL and transferrin saturation were abnormal in hospitalized patients in comparison with those of the non-hospitalized. Several other blood biomarkers such as mean corpuscular haemoglobin concentration, alanine transferase, lactate dehydrogenase, triglycerides and cholesterol were abnormally higher in more than 10% of all patients. Similar were the levels of inflammatory markers suggesting that there was ongoing inflammation in spite of clearance of the virus from the body. The multi-organ MRI showed that heart impairments such as myocarditis (11%) and systolic dysfunction (23%) were prominent. Other organ abnormalities in the lungs (33%), liver (10%), kidneys (12%), pancreas (17%) and splenomegaly (6%) were observed. The results also showed that 66% of patients have one or more organ impaired and 25% have varying degrees of overlapping multiple organ-related issues. Organ impairment was more common in hospitalized individuals, along with inflammation in kidneys, and ectopic fat in the pancreas and liver than in non-hospitalized.

Lasting influence

A systematic review of 1,169 studies evaluating the long-term outcomes of SARS-CoV-2, SARS and MERS threw up interesting insights. 18 studies reported on lung function, in which abnormalities were detected in the diffusion capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC) and total lung capacity (TLC) even after 6 months of COVID-19 infection. Five studies reporting on exercise tolerance outcomes and assessing cardiopulmonary exercise test and 6-minute walking distance (6MWD) showed a pooled difference of lower or impaired exercise tolerance post-infection than the baseline subjects. Six studies reported the prevalence of psychological conditions in COVID-19 survivors where post-traumatic stress disorder (PTSD) was found in 38.8% of patients, depression in 33.2% and anxiety in 30.04%. All these studies
give a clear impression of reduced quality of life post-infection and underline the need for much larger continued studies to develop better prediction and prognosis for treatment and management.

These findings will have lasting influence and implications on several clinical and research approaches. The first aspect is that as the countries are going to have a second wave of infections, any study or research must include long-COVID. The second is that multi-organ impairment assessment, along with biochemical and image analysis, must be done to understand the impact on the quality of life post-infection. The third important aspect is that longitudinal studies are needed to improve multidisciplinary care. The clinical practice implications for COVID-19 management is that there is a need for medium- and long-term follow up of patients for extrapulmonary sequelae. Clinicians will also have to consider the impact of COVID-19 vaccines.

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