Dr.Satish Ranjan is a Molecular Immunologist based in Germany and Group Leader (Translational Immunology) at Institute of Advanced Materials, Sweden.

Covid-19-the Coronavirus disease-2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019 has spread with profound effect on the lives and health of people around the globe. Until now millions have been infected and many have lost their lives due to this infectious disease. Recent pieces of evidence have shown that many people have a range of persistent symptoms after the acute SARS-CoV-2 infection that remains for a longer period of time and this condition is now coined as long covid by recognized research institutes. The most astonishing fact that emerged from several studies is that like acute covid-19, long covid can involve multiple organs and can affect many systems including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. It can have a differential impact on males and females and need proper post-Covid-19 management to systematically address the complications.

Long-Covid/Post-Covid

On 5 May 2020, an account was published in BMJO opinion where an infectious disease professor shared his experience of seven weeks on a “rollercoaster of ill health” following covid-19. After this publication, the term “Long-covid” gained widespread attention. This patient-made term long covid was then made popular following the rise in the use of #LongCovid on Twitter.  Since then a huge number of peer-reviewed articles have been published highlighting a post-covid-19 syndrome that can last for many weeks after the acute infection. Long covid is now a recognized term in scientific literature. The National Institute for Health and Care Excellence (NICE), UK defines long covid as the symptoms that continue or develop after acute covid-19 infection and which cannot be explained by an alternative diagnosis. This term includes ongoing symptomatic covid-19, from 4 to 12 weeks post-infection, and post-covid-19 syndrome, beyond 12 weeks post-infection. Whereas, the National Institutes of Health (NIH), USA uses the US Centers for Disease Control and Prevention (CDC) definition of long covid, which describes the condition as sequelae that extend beyond four weeks after initial infection.

Common and Clinical symptoms of Long-Covid/ Post-Covid-19

Patients with covid-19 have shown a wide range of clinical manifestations ranging from asymptomatic infection to fatal disease. The SARS-CoV-2 virus is responsible for causing covid-19 enters into cells via the angiotensin-converting enzyme 2 (ACE2) receptor. After internalization the virus undergoes replication and maturation in infected cells, provoking an inflammatory response that involves the activation and infiltration of immune cells by various cytokines. Cytokines are small proteins that regulate the activation and function of various immune cells and once cytokines are produced in large quantities they can cause damage to our own cells by hyper-activating the immune cells which act against our own healthy organs. The ACE2 receptor is present in numerous cell types throughout the human body, including in the oral and nasal mucosa, lungs, heart, gastrointestinal tract, liver, kidneys, spleen, brain, and arterial and venous endothelial cells, therefore infection by SARS-CoV-2 can cause damage to multiple organs.

The impact of covid-19 thus far has been unparalleled, and long-term symptoms could have a further devastating effect. People with long covid exhibit involvement and impairment in the structure and function of multiple organs. Numerous symptoms of long covid have been reported and attributed to various organs. Common symptoms and symptoms associated with vital organs are listed in Table 1.

Important Symptoms and Possible Mechanisms:

Fatigue

Fatigue is more profound than being overtired; it is unrelenting exhaustion and a constant state of weariness that reduces a person’s energy, motivation, and concentration. More than 60% of patients reported ongoing fatigue at 12 months following recovery after infection with SARS-CoV-2. Fatigue is found to be the most common persisting symptom regardless of the severity of the acute stage of covid-19. Several studies have found that both hospitalized and non-hospitalized patients have reported ongoing fatigue for more than 2 months following the onset of illness.

Several factors could be responsible for chronic fatigue but the direct SARS-CoV-2 infection of skeletal muscle, resulting in damage, weakness, and inflammation to muscle fibers and neuromuscular junctions may be the most potent factor. Negative psychological and social factors associated with the covid-19 pandemic have also been linked to chronic fatigue.

Dyspnea

Breathlessness is common in people with long covid. Several abnormalities like changes in diffusion capacity for carbon monoxide, total lung capacity, forced expiratory volume, forced vital capacity, and small airway function has been seen in hospitalized covid-19 patients which continued for months even at the time of discharge. This suggests that lung function in people who have had covid-19 may take time to recover.

As covid-19 is principally a respiratory illness so the acute illness can cause substantial damage to the lungs and respiratory tract via SARS-CoV-2 replication inside these cells that can damage these cells and can cause an intense immune and inflammatory reaction. Many patients who overcome the acute infection may develop long-term lung abnormalities, leading to dyspnea however many have no signs of permanent or long-lasting lung damage. It is likely that those at higher risks with prior breathing problems and old-aged people can develop long-lasting damage in  the lungs.

Cardiovascular abnormalities

Many people have persistent cardiovascular abnormalities post-covid-19 recovery. Several studies have shown cardiac involvement, ongoing myocardial inflammation, and elevated serum troponin levels in many people with covid-19 even after 2 months of initial infection. Many people have chest pain and those considered at low risk of severe covid-19, such as young, competitive athletes, have also been found to have residual myocarditis (inflammation of heart muscle) after recovery from covid-19.

Cognition and mental health

The greatest and most negative impact of the current pandemic is on the mental health of people. Many people who had covid-19 are exhibiting long-term psychiatric symptoms including post-traumatic stress disorder (PTSD), depression, anxiety, and obsessive-compulsive symptoms following recovery from the acute infection. Quarantine, isolation, and social distancing also have damaging effects on mental health and cognition.

Several studies have reported that the longer a person is confined to quarantine, the poorer the outcomes on their mental health. Longer periods of isolation and the inability to work can cause anxiety, loneliness, and financial concerns, and living through a global health crisis can lead to avoidance behaviors and behavioral changes. The mental health of the older population is greatly affected by social distancing and similar measures. The pandemic has exerted extra unfavorable effects on loneliness, physical activity, and mental health that was not the situation before 2020 for most people across the globe.

Sleeplessness is also commonly reported following recovery from covid-19, with many studies finding poor sleep quality and sleep disturbances to be frequent following recovery from acute illness.

Effect of variants on Long Covid

The coronavirus has undergone many mutations and has emerged into various variants with different degrees of disease severity. New covid-19 variants will continue to emerge and spread as we progress through the pandemic, for example, the Eta, Lambda, Delta, and Omicron variants have arisen and have caused mild to severe diseases across the globe. Many of these variants like Delta and Omicron have caused long-covid and the ability of these viral strains to inflict long-term complications needs to be examined fully. To speculate, it may be that one variant causes more damaging long-term effects than others. So, the patients infected with such a variant may develop long covid symptoms which need to be monitored closely and they may require additional support, as well as more rapid and intense treatment strategies to combat their long term symptoms.

Implications for male and females facing long-covid/post-Covid-19

Several studies and real-world experiences suggest differences in the degree of disease severity and differences in complications following acute infection by SARS-CoV-2. While it has been reported in several studies and seen across many places that SARS-CoV-2 infection has led to more severe symptoms in males than females. Thus following infection males have become more symptomatic than females but after infection differences have been noticed in long-covid/post-covid complications. It has been surprisingly noticed that females with asymptomatic infections are developing more obvious symptoms after 4-12 weeks. Therefore it is highly likely that females who have not developed any symptoms during prior infection may be experiencing the long-covid symptoms. Special attention needs to be paid in such cases by females and they should go for proper treatment and management of post-covid complications.

Treatment and management of long covid

Several guidelines have been made by international bodies like NICE, WHO, CDC, etc. which focus on proper diagnosis, proper treatment, proper care, and scientific and evidence-based management of long-covid. WHO and the Long Covid Forum Group agree that for long covid treatment proper clinical characterization should be done and further research and development of therapeutics should be undertaken. In my opinion, it is very important to understand the exact clinical manifestation of the patient having long-covid/ post-covid symptoms and minimal drug-based therapy should be applied only in cases of absolute necessity so that possible adverse effects of current treatment should be avoided. More emphasis should be on natural therapy which has immense potential to treat such manifestations. Self-treatment and over-treatment by doctors should be completely avoided.

Clinical characterization of patients with long covid is essential to provide appropriate treatment options and for this good and affordable diagnostic labs should be set up in every part of the country. More research should be undertaken to understand why certain disease phenotypes arise in different individuals and what could be the best therapy for them.

The guidelines for treating and managing long covid will undoubtedly evolve as new evidence comes to light but several complications like breathing problems, sleep-disturbances can be self-managed by practicing healthy lifestyles and doing yoga, physical exercises, and adopting other natural therapy measures. Government should make a future roadmap to deal with long-covid complications and proper diagnostic and treatment infrastructure should be created at all levels to cater to the need of the people. Online counseling for mentally disturbed people should be provided and scientific evidence-based measures should be adopted to avoid further damage to the mental health of the people.

Special focus should be paid to the mental health of the children who have suffered the most not only due to Covid-19 but also due to longer restrictions measures. With more pieces of evidence suggesting that children have better immunity against the virus, so minimal restrictions should be imposed on them and schools should be re-opened as before and if required in the future decisions regarding the closing of schools should be taken on scientific evidence rather than on emotional basis and restricting them at home and leading to further deterioration in their mental health.

Altogether society needs to move ahead and get out of post-covid complications and mental trauma by adopting a holistic and scientific approach and the government should play a positive role and create all the required infrastructure and facilities needed to address these problems.