Is Long COVID Unique Only to SARS-CoV-2 Coronavirus?

Authored By: Venkat Rao

In the immediate aftermath  of COVID-19 pandemic there was barely a mention of long-term effects of coronavirus infections in the published medical literature, but in the aftermath of the pandemic, a slew of publications report on what is termed, Long COVID-19. So, what exactly is Long COVID-19? And, is only SARS-CoV2 virus unique inducing an enduring and long-term pathology of what is generally regarded as a short-term infection?

Long COVID Disease remains an Unquantifiable Burden on Global Health

According to the US Centers for Diseases Control and Prevention, Long COVID is a chronic medical condition often occurring in individuals who have had severe COVID-19 illness, although anyone who gets the disease could end up with the medical condition. In vast majority of cases, viral infection is  for a short duration with disease symptoms resolve and subside within a two-week period. Some individuals may later develop Long COVID without contracting a new infection where disease symptoms ranging from mild to severe may reemerge, persist, and worsen  over weeks and months. According to a recent British study nearly 1 in 10 UK adults think they could have Long COVID but are not sure. Based on an analysis of General Patient Survey of a random sample of nearly 760 thousand adults, the study found 9.1% of the respondents were unsure and this group mostly consisted of females, LGBTQ, living in a socioeconomically backward area and being a care provider, or a parent of an individual with the long-term disease condition.

The University of Southampton study surprisingly points out the persistent confusion regarding the chronic health condition years after the pandemic. With the pandemic years receding in the rearview mirror of global public health, these results imply lack of awareness on the long-term impact of COVID-19 and existing barriers to accessing diagnosis and treatment and support as the underlying reasons for the persistence of Long COVID.

Meta analysis comparing the differences in the symptoms of Long COVID caused by different strains of SARS-CoV-2 found that the more dominant Delta and Omicron variants prevailed widely in many countries around the world, whereas the Alpha variant appeared only in a few countries and was relatively a mild variant. Data pooled from various disease reporting sources on the viral variants indicated that the general symptoms of fatigue were reported by more than 60% among patients infected with the Alpha variant, which was higher compared to the other two dominant strains, whereas cases reporting myalgia was higher among Long COVID patients infected with the Omicron variant compared to the wide-type strain.  Reported difficulty to sleep was low among Long COVID patients infected with the Delta variant but was high among the Omicron and wild-type strain infected patients. Although for the most part the overall symptoms of Long COVID among patients were comparable no matter which strain of the virus contributed to the disease, there were notable differences in key clinical symptoms across the global population, the reason for which remains unclear.

It is important to differentiate Long COVID disease from the lingering symptoms of COVID-19  even after the cessation of the disease. For instance, hospitalized patients recovered from severe cases of COVID-19 even after 6 months reported pulmonary function dysfunction showing persistent lung CT scan abnormalities, compromised lung breathing capacity, and reduced oxygen update in the study population. Patients with other health conditions, age and females were more susceptible to lung dysfunction compared to other groups in the study.

It is unclear why SARS-CoV-2 viral infection create long-term clinical problems in about 10 percent of the COVID-19 disease-recovering adults, and why women are at a higher risk of getting Long-COVID compared to men.

A constellation of clinical symptoms broadly grouped as chronic fatigue syndrome (CFS) is unique to Long-COVID. These symptoms include fatigue, shortness of breath (dyspnea), joint pain, muscle pain (myalgia) chest pain, cough, complete loss of sense of smell (anosmia), distorted or altered sense of taste (dysgeusia), headache, depression, anxiety, memory loss, difficulty to concentration and difficulty sleeping (insomnia) are frequent medical conditions reported by Long COVID patients. 

With over 700 million cases of COVID-19 in the official records globally of which 675 million recovered from the disease, a 10 percent approximation of Long COVID based on the a previous report means there are nearly 68 million individuals still suffering from Long COVID and exhibiting some or all the symptoms listed above. The global public health disease burden due to Long COVID is enormous with the path to total recovery from the pandemic remains a distant milestone.

Some public health surveillance reports indicate that as of 2025, Long COVID remains to be a significant global public health concern with over 400 million people reported some form of long-term disease symptoms corelating with the virus, or its genomic fragments capacity to remain persistent in the tissue of COVID patients was indicated as the causative factor for Long COVID. Investigations have revealed presence of SARS-CoV-2 virus or its viral fragments in the skin, appendix, and breast tissue of some Long COVID patients. Interestingly, the viral deposits were mostly in non-respiratory tissues such as adrenal glands, small intestine, lymph nodes, heart tissue and the sciatic nerves.

Persistence of SARS-CoV-2 in brain tissue was found during autopsy as late as 230 days after the onset of infection in unvaccinated patients who died of severe infection. The unique property of SARS-CoV-2 virus to remain persistent in multiple tissues, organs post infection seems to be the most plausible causative factor behind Long COVID.

A fascinating aspect of SARS-CoV-2 virus is that the short-form of COVID, a predominantly upper respiratory tract infection lasting for a week or two, has a chronic version of the disease that bears little resemblance to the short-form of COVID in the pandemic.

Long COVID Symptoms Cover a Wide Spectrum of Disease Symptoms Way Beyond The Lung and Upper Respiratory System

Long COVID is a disease syndrome with multiple and often unrelated symptoms to include fatigue, difficulty to sleep, memory loss, depression and anxiety which are seldom observed in the short-term COVID. However, many other symptoms generally associated with the short-term version are also reported by patients with Long COVID.

Medical surveillance for early detection of Long COVID is key to assessing the size and scope of this long-term burden. Smart technology tools and solutions are key to implementing an effective medical surveillance program.

According to a recent report the heart rate and inactivity data from a smartwatch can be used to detect distinct symptoms of initial stages of Long COVID disease. The investigative report used over 20,000 behavioral and physiological data from wearable devices such as smartwatch to identify individuals by self-reported persistent fatigue and shortness of breath following recovery from COVID-19 disease. More than 120,000 volunteered to participate and shared data from their watches with the researchers. Using a symptoms free control group as the baseline the study found a higher resting heart rate and lower daily step counts even at least three weeks before SARS-CoV-2 infection.

Smartwatch-derived data identified persistent fatigue and shortness breath even before the infection, making an insightful conclusion that persistent fatigue and shortness of breath reported by Long COVID patients was linked to the pre-existing lower fitness levels or health conditions. By implication, physiological and behavioral data such as heart rate, physical activity, step count and sleep duration captured from wearable devices could identify risk factors and population sub-groups likely to suffer from lingering, long-term adverse consequences of COVID disease.

Viruses are ubiquitous in nature and part of our daily lives. Viral infections for the most part clear out within a few days by our body’s immune system. Although most disease symptoms caused by the viral infection disappear, the virus may still reside within the body in a latent state without inducing any of the pathological symptoms. Virus may remain in a dormant state for many years without causing any symptoms but may reactivate due to external and internal factors.

Prominent examples are Herpes Simplex Virus, which once get infected remains dormant in the body for the rest of  their lifetime and triggered to reactivate due to multiple reasons such as stress, other illness, and irradiated skin.

Another common example is the Varicella Zoster Virus which causes chickenpox and then remains dormant in the host’s nerve cell for many years and reactivate at a much later time as shingles. Shingles, a common disease in older adults, is actually the eruption of the chicken pox virus that they contracted while as children, only to reappear as shingles.

One final example is the Human Immunodeficiency Virus (HIV) that causes AIDS. When someone gets infected with HIV the virus stays with them through their lifetime. HIV-infected people do not automatically develop AIDS diseases, as the virus remains latent in the white blood cells. Dormant HIV is triggered for reactivation due to genetic and external factors leading to AIDS disease.

What is unique about SARS-CoV-2 is its capacity to adversely impact human body well beyond the lungs taking residence in other vital organs such as heart, blood vessels, intestines, brain, kidney, genitals, and body fluids such as saliva, urine, semen, milk, mucus, and cerebrospinal fluid. It is puzzling, however, that the virus is detected only in urine, stool besides lungs in COVID-19 patients.

A broad range of Long COVID disease symptoms beyond the lungs and respiratory track is attributable to the persistent presence of the virus in other vital organs causing symptoms besides respiratory disorders including neurological, cardiovascular, intestinal and kidney malfunctions.

Long COVID remains a poorly understood carryover disease burden of the pandemic and its long-term costs to health security and global health remains unknown.