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Published On: December 15th, 2020By Categories: Fundamental Science
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Many infectious diseases can cause persistent symptoms and complications after the infection itself has cleared. These can range from impaired memory that improves over weeks, to general weakness that improves over months, to chronic organ dysfunction.

For example, cough and shortness of breath are common symptoms of community acquired pneumonia (an infection of the lungs). Even after successful treatment, these symptoms can persist for weeks or longer along with signs of lung injury1.

The chance of developing post-infection symptoms generally depends on2:

  • – How severely ill the person became
  • – How long they were ill
  • – Their age
  • – Other medical conditions they had
  • – The type of organism causing the infection

Coronavirus Disease 2019 (COVID-19), an infection caused by SARS-CoV2, also appears to carry a risk of post-infection symptoms, commonly called “Long COVID”. This is an area of active investigation. At the time of this article’s preparation, the definition of Long COVID, its cause, how symptoms should be categorized, and how they should be managed are areas of active investigation and debate3,4. Currently, Long COVID is an umbrella term for a constellation of persistent symptoms that share a trigger: COVID-19 infection.

Our current knowledge on Long COVID is limited by a lack of completed and peer-reviewed studies. We hope to understand more as more data is released, but understanding the diverse range of Long COVID symptoms will require longitudinal (long-term) studies.

Below is a non-exhaustive summary of the current knowledge. We would like to emphasise the phrase current knowledge, because knowledge will evolve as more studies are done. Furthermore, we would like to emphasize that the information provided herein is not intended to replace medical advice. If you feel like you are experiencing some of the symptoms listed below, please consult a medical professional.

How long do symptoms have to last to count as Long COVID?

Current evidence suggests that the duration of COVID-19 symptoms can vary greatly. Based on reports from the World Health Organization (WHO), the typical recovery time from mild COVID-19 infection seems to be around 2 weeks, while recovery from severe infection may take anywhere from 3-6 weeks5. This represents the end of the infection, however, and not returning to baseline health.

The UK’s NICE (The National Institute for Health and Care Excellence) has also set forth guidance on Long COVID, and defined it as:

“signs and symptoms that develop during or following an infection consistent with COVID-19 which continue for more than 12 weeks and are not explained by an alternative diagnosis”6

What are the typical symptoms of Long COVID? 3,4,7

  • – Cough
  • – Shortness of breath
  • – Fatigue
  • – Muscle and/or joint pain
  • – Headache
  • – Lost sense of smell and/or taste
  • – Confusion or difficulty concentrating
  • – Low-grade fever
  • – Stomach/gastrointestinal upset
  • – Rash
  • – Depression
  • – Anxiety / Post-traumatic stress

This is not an exhaustive list, and severity of symptoms can also vary from one day to another3,4,8. Furthermore, some of these symptoms may not be a direct consequence of the viral infection and its ensuing immune response, but until better data allows us to have a proper understanding of Long COVID, they will be included in current literature.

How common is Long COVID?

In patients who were hospitalized with COVID-19, persistent symptoms after discharge are common and their severity/duration depends heavily on the severity of illness. Studies have so far shown that more than half of patients hospitalized with COVID-19 may have one or more persistent symptoms 3 months after discharge4,9. This number may be higher in those who required intensive care, or lower in those who experienced mild symptoms.

In people who had COVID-19 but were not hospitalized, high quality data is still pending. One commonly cited study from the UK (which used a publicly available app) showed 13.3% of people remaining unwell beyond 4 weeks from infection, 4.5% having symptoms beyond 8 weeks, and 2.3% beyond 12 weeks7. However, this study had limitations and the investigators counted people who stopped using the app as “recovered” if they had less than 4 symptoms at their final log (a risky assumption). The article also requires peer review. Higher quality data will hopefully be available over time, including the Canadian CANCOV study, and international efforts like the ISARIC COVID19 long term follow up study10.

Like some other infectious diseases, the duration of acute COVID-19, as well as the person’s age and pre-existing medical conditions seem to increase the risk of developing Long COVID. Older adults with multiple medical conditions are most at risk, but young adults who were previously healthy can also develop it11,12.

What causes Long COVID?

Currently, the mechanisms that lead to Long COVID symptoms are not well understood. Many Long COVID symptoms in people with severe or mild cases of COVID-19 are thought to be associated with injury to lungs, heart, nervous system, and other organs3,13,14.

SARS and MERS infections, which are caused by viruses in the same family as COVID-19, are also known to cause some of the physical symptoms we see in Long COVID15,16. The shortness of breath that’s commonly seen with Long COVID may be due to injury to alveoli (small sacs in the lungs that help store and exchange oxygen), which is a mechanism that was also seen in SARS15. Given Long COVID’s distribution around the body and risk of causing clots, it’s possible for it to affect organs much differently than might be expected from a typical respiratory virus4.

It’s also important to understand that many Long COVID symptoms are not unique to COVID-19 itself and they can happen with other infections or viral illnesses. For example: Tissue/organ injury can be caused by any severe infection and our body’s immune response to that infection17. Even needing to be managed in an intensive care unit (ICU) is associated with some of the symptoms seen in Long COVID, called Post-Intensive Care Syndrome (PICS)18,19. PICS can include muscle weakness, cognitive problems, and even mental health issues18. Depending on the severity, people with PICS may need rehabilitation and some effects like nerve damage may be permanent.

Another possible overlap is Post-Viral Syndrome (also called Post-Viral Fatigue)20. This is an already known phenomenon that affects a small number of people after viral infections. As the name suggests, the common symptoms are feeling tired and weak, though this is typically milder than what’s seen in Long COVID. For most people, Post-Viral Syndrome improves over time.

Many other mechanisms have been proposed for Long COVID symptoms, especially in people who had a relatively mild acute infection. These include: delayed clearance of the body’s inflammatory/autoimmune response to the virus, as well as physiological stress experienced by various tissues3.

It’s possible people with Long COVID may have more than one mechanism behind their symptoms. At this time, it’s simply too early to define absolute categories on the mechanisms behind Long COVID. More research is needed.

How is Long COVID managed?

At this time, there is no single therapy for Long COVID, and very little data on effective treatments exists.

People with signs of organ injury (especially those who required hospitalization) should see their family physician and may need to be referred to specialists. Those who had moderate to severe disease may require rehabilitation3.

People who had mild COVID and persistent symptoms may benefit from rest, light aerobic exercise, and gentle symptom control using some medications while they gradually improve3,8. Examples of medications include using expectorants (e.g. guaifenesin) for a wet cough, analgesics (e.g. acetaminophen) for pain or fever, or prescribed inhalers for episodes of shortness of breath. These should be discussed with a family physician or community pharmacist first.

More than anything, pacing and setting modest expectations are important. We’re learning about Long COVID as we try to help patients through it, and while symptoms can be substantial, many patients seem to improve over time.

National and international support groups for Long COVID also exist, and can be found online.

What are the next steps?

  • 1) Support patients with Long COVID, regardless of the etiology of this illness. It starts with better recognition.
  • 2) Better studies to quantify and explains Long COVID symptoms. Long COVID is a useful umbrella term that’s simple to understand and allows easy peer support and advocacy. However, the mechanisms behind the symptoms need to be teased out in order to find management strategies. This may lead to multiple different pathologies being identified.
  • 3) Continue to practice social distancing, mask wearing, and hand hygiene to reduce the burden of acute COVID and Long COVID.

References

  • 1. Brandenburg, J. A. et al. Clinical presentation, processes and outcomes of care for patients with pneumococcal pneumonia. J. Gen. Intern. Med. 15, 638–646 (2000).
  • 2. Waterer, G. Recovery from community acquired pneumonia: the view from the top of the iceberg. Eur. Respir. J. 49, (2017).
  • 3. Greenhalgh, T., Knight, M., A’Court, C., Buxton, M. & Husain, L. Management of post-acute covid-19 in primary care. BMJ 370, (2020).
  • 4. del Rio, C., Collins, L. F. & Malani, P. Long-term Health Consequences of COVID-19. JAMA (2020) doi:10.1001/jama.2020.19719.
  • 5. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 24 February 2020. Link here.
  • 6. NICE, SIGN and RCGP set out further details about the UK guideline on management of the long-term effects of COVID-19 | News and features | News. NICE Link here.
  • 7. Sudre, C. H. et al. Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. medRxiv 2020.10.19.20214494 (2020) doi:10.1101/2020.10.19.20214494.
  • 8. Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin. Exp. Res. 1–8 (2020) doi:10.1007/s40520-020-01616-x.
  • 9. Carfì, A., Bernabei, R., Landi, F. & for the Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA 324, 603 (2020).
  • 10. ISARIC Global COVID-19 Long term follow up study • ISARIC. Link here.
  • 11. Tenforde, M. W. et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020. Morb. Mortal. Wkly. Rep. 69, 993–998 (2020).
  • 12. Iacobucci, G. Long covid: Damage to multiple organs presents in young, low risk patients. BMJ 371, (2020).
  • 13. Zhao, Y.-M. et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 25, 100463 (2020).
  • 14. Living with Covid19. Link here.
  • 15. Zhang, T., Sun, L. X. & Feng, R. E. [Comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease 2019]. Zhonghua Jie He He Hu Xi Za Zhi Zhonghua Jiehe He Huxi Zazhi Chin. J. Tuberc. Respir. Dis. 43, 496–502 (2020).
  • 16. Tansey, C. M. et al. One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome. Arch. Intern. Med. 167, 1312–1320 (2007).
  • 17. Sepsis – Symptoms and causes. Mayo Clinic Link here.
  • 18. SCCM | Post-intensive Care Syndrome. Society of Critical Care Medicine (SCCM) Link here.
  • 19. Loss, S. H. et al. The reality of patients requiring prolonged mechanical ventilation: a multicenter study. Rev. Bras. Ter. Intensiva 27, 26–35 (2015).
  • 20. Post-viral fatigue: a guide to management | North Bristol NHS Trust. Link here.

About the Author: Amir Imani, PharmD

Amir Imani, PharmD is a clinical pharmacist serving rehab patients in Bridgepoint Active Healthcare, and an instructor at the University of Toronto’s Faculty of Pharmacy.