The Covid-19 pandemic continues its seemingly endless parade across the world, with the virus variants and their sub-lineages still walking the ramp while springing surprises with fresh spike protein outfits and changes in other antigen accessories. While face masks and vaccines strive to slow down the pandemic and reduce deaths, there are concerns about survivors who are manifesting long-term effects of the infection, even after the initial acute phase has subsided.
This phenomenon, popularly known as Long Covid, has been observed since the initial waves of 2020 and appears to continue with the variants of 2021. How much of this prolonged affliction occurs with the Omicron family of variants still needs to be assessed, since the initial illness caused by them has been reported to be less severe. That may be because the virus has tempered its virulence or because its effects have been blunted by the immunity acquired from prior infection or vaccination. In either case, the risk of Long Covid appears to be less with Omicron than with the earlier forms of the virus.
The definition of Long Covid has taken time to evolve. The World Health Organisation (WHO) defines it as Covid attributable symptoms manifesting three months after the acute infection. According to WHO, “The post-Covid 19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from the onset of Covid-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis.” The Centers for Disease Control (CDC), USA, regards symptoms lasting beyond four weeks after the acute illness as indicative of Long Covid. Britain’s National Health Service (NHS) categorises subsets as ‘ongoing symptomatic Covid-19’ (4-12 weeks) and ‘post-Covid-19 syndrome’ (over 12 weeks).
Scientific reports, published from across the world, differ in their estimates of Long Covid depending on which criteria they use. A recent analysis by CDC, of millions of health records, reported a 20 per cent estimate of this affliction among Covid survivors. That may have missed out persons who could not or would not access healthcare for various reasons. An earlier household survey by CDC, reported in June this year, identified a rate of one in three persons. A meta-analysis of pooled global data from several studies, published in March 2022, places the prevalence of Long Covid close to 50 per cent of all survivors. Whatever the actual percentage, the overall numbers are a matter of great concern since the health and wellbeing of vast numbers of Covid survivors seems compromised.
The long term health effects of Covid may arise from one or more of the following causes: (1) effects of the organ damage directly caused by the virus; (2) residual impact of injury caused by the vigorous immunological response mounted by the body while combating the virus; (3) aggravation of other associated health conditions, especially diabetes, by Covid-triggered inflammation; (4) neglect of other health conditions by medical care focussed only on Covid management; (5) side effects of medicines and technologies used for Covid care, such as steroids and psychological stress induced by intensive care. Reactivation of a latent infection with the Epstein-Barr virus has also been incriminated as a cause of Long Covid.
Since chronic fatigue has been noted with some other viral infections, and long term illness has also been observed with the Coronavirus related to SARS-1 and MERS, much of the Long Covid appears to be related to the interactions between the virus and the human body. The early tendency of doctors to dismiss complaints of Covid survivors as purely psychological has proved to be an erroneous and unfair assessment.
Several clinical features of Long Covid have been described, involving ailments of different organs — from the brain and the heart to the gastrointestinal system and the pancreas. Apart from direct tissue damage caused by the virus, there is some evidence to suggest that the tenth cranial nerve (The Vagus) may be affected. It is the longest cranial nerve, so named because it is the ‘wanderer’ that courses from the brain to the chest and abdomen to innervate and regulate many vital organs.
While several organs and body functions may be affected by Long Covid, its impact on the heart and blood vessels has attracted considerable attention. Inflammation of the heart muscle (‘myocarditis’) may result from either a direct effect of the virus damaging the muscle fibres or as a result of immunological injury caused by the body’s own defences. The pericardium, a membrane covering the heart, too can be inflamed (‘pericarditis’). Heart muscle damage has been detected in persons who died of Covid. Among the survivors, evidence of cardiac involvement comes from a rise in blood levels of enzymes released by the damaged heart muscle, decreased pumping ability of the heart muscle noted by echocardiography or radionuclide imaging, and evidence of muscle fibre damage observed by magnetic resonance imaging (MRI). Impaired cardiac function is reflected in symptoms of fatigue, decreased exercise tolerance and deep burning chest pains, though clinical signs of heart failure are rare in persons without pre-existing heart disease.
Incidence of cardiac involvement in Covid is difficult to quantify as only a section of Covid survivors may undergo detailed evaluation. In the pre-Omicron era, Valentina Puntmann in Frankfurt studied 100 consecutive patients, around 10 weeks after they tested positive for the virus. They performed a cardiac MRI, with a gadolinium contrast agent. They observed cardiac abnormalities in three out of four patients. Impaired pumping action of the heart, inflammation or fibrosis of the heart muscle and pericarditis were among the findings. Most patients got better by six months, though the symptoms lasted up to a year in a few.
Abnormalities of heart beat too may occur. The vagus nerve, which has a slowing effect on the heart rate, usually keeps the heart beat in check. With that inhibitory effect gone and a stressed body pumping adrenaline and other catecholamines, the heart can start racing madly. This may be aggravated when a person stands — a condition called Postural Orthostatic Tachycardia Syndrome (POTS). In this affliction, the heart rate rises by more than 30 beats in adults and by more than 40 beats in children, within 10 minutes of standing up. Irregularity of heart beats too can occur (‘missed beats’ or ‘arhythmias’).
The heart may also get stressed when the lungs are affected by Covid. Fibrosis of the lungs creates greater resistance for the heart when it pumps blood to them and the damaged lungs too do not efficiently oxygenate the blood that returns to the heart. Blood clots that are formed due to damaged blood vessels in the acute phase of Covid may later dislodge when the person becomes active. When clots from the veins travel to the blood vessels of the lungs (‘pulmonary embolism’), they can cause severe circulatory collapse. Due to blood vessel damage and greater tendency to form clots, Covid survivors still manifest a higher risk of heart attacks even a year after the initial infection.
The inner lining of blood vessels (endothelium) is a dynamic structure, which responds to varying conditions of blood flow requirements by helping the artery to dilate or constrict while maintaining blood pressure in a desirable range. Covid has led to endothelial dysfunction, resulting in loss of ability of blood vessels to dilate when needed. This can lead to high blood pressure, accelerated atherosclerosis and heart attacks. Covid has also been observed to increase the risk of long-term erectile dysfunction in males, due to loss of endothelial vasodilatation in the blood vessels of the male genitalia.
While several disorders of heart and blood vessels have been observed in Long Covid, it need not be feared that most survivors of Covid will experience them or that their effects will be permanent. Many persons who manifest effects of Long Covid recover over time, especially if the initial infection was mild and there is no reinfection. The time taken to recovery will vary depending on severity of initial infection, age of the person and associated co-morbidities. It is best to avert the risk of infection by wearing masks as advised and getting vaccinated to avoid severe illness that may set the stage for Long Covid. No specific treatments are as yet available but the study of Long Covid is still an evolving field. As of now, ‘mask up’ and ‘get vaccinated’ is the best preventive advice.
(Prof. K. Srinath Reddy, a cardiologist and epidemiologist, is President, Public Health Foundation of India (PHFI). The views expressed are personal)