Coughs, sudden fever, shortness of breath.

We’ve become familiar with these red flags now. Nearly 1 in 20 patients who test positive for COVID-19 die (1). For those with severe cases requiring hospitalization, the death rate is nearly 1 in 4, found a New York University Langone Health study (2). But for those who do recover - even those never hospitalized: is it really over? Is the scare over?

Unfortunately, that might not be the case.

Chronic fatigue, anxiety, joint pains.

Debilitating symptoms are being reported by former COVID patients, often months after supposedly recovering. “Long Covid” is the name being thrown about. While many of those with mild coronavirus infections recover within a fortnight, it’s becoming clear that for many others the infection is a long-term illness, according to a report from the UK NIHR (3). And it’s not like this seems to be a rare thing at all. A study from a hospital in Rome found that nearly 90% of recovered patients reported persistence of at least 1 symptom even after consecutive negative test results (4). 9 in 10 people. Why is this the case? As with so many things with this virus, the causes behind this are unclear, but what is becoming clear is the need to better define recovery and accordingly adapt care. That said, we aren’t without clues.

Chest pain, breathing difficulties, depression.

Since the illness begins as a respiratory infection, the obvious organ of research to better understand “long COVID” has been the lungs. Especially in the case of severe infections, lung scans show the extensive inflammation and scarring even after the virus has been cleared from the patients’ bodies. “Unfortunately, sometimes the scar never goes away,” says clinical radiologist Ali Gholamrezanezhad at the University of Southern California (5). While such cases are likely to be much more prevalent in those with severe infections, nearly 50 million people have been infected worldwide at time of writing. Considering such enormous numbers, clinicians are predicting a surge of long-lasting illnesses and disabilities requiring treatment and support. Of course, things just get worse when we look into the systemic effects of COVID-19 infection.

Nerve damage, kidney damage, heart damage.

Although COVID-19 is largely a respiratory disease, there is increasing evidence to suggest it’s multi-organ nature, particularly in those with severe cases. New studies are showing that this coronavirus seems to wreak havoc in the cardiovascular, neurological, and osteogenic systems as well as just about anything else in the body (6,7). While a compromised immune system is a suspected key predictor of COVID-19 susceptibility, many patients are finding their immune systems to be weakened post recovery. The coronavirus strain responsible for the 2002-04 SARS outbreak is known to do this by inhibiting the production of a group of proteins essential for regulation of immune responses called type I interferons (8). The capsid of the virus which is a “buckyball” looking protein structure which encapsulates the virus’s DNA has been found to interfere with an internal cellular mechanism to signal for the production of type I interferons to stimulate the body’s immune response.

However, things can also go the other way round. The immune response is actually overstimulated in some patients. Aside from the potential to induce a cytokine storm as I explained in my past post on obesity, emerging research has raised the possibility of auto-antibodies targeting multiple organs (9). What are auto-antibodies you ask? While antibodies are what our adaptive immune system produces to specifically target and destroy invaders of the body such as viruses, auto-antibodies are abnormalities that attack targets on our own body. That basically means our immune system is launching an attack on our own body with the same ruthless efficiency it should be mounting on the disease.

It’s becoming ever-clearer that this disease is able to inflict long-lasting damage even to those who’ve recovered even mild infections. Academics and clinicians warn us that we will suffer from the impact of this pandemic for years to come. Everyday, we learn about how this coronavirus is ravaging our communities - especially our most vulnerable. However, it is only through fully understanding the devastation we are left with, that we are able to know how to heal.

References:

1. COVID-19 Map [Internet]. Johns Hopkins Coronavirus Resource Center. [cited 2020 Jul 2]. Available from: https://coronavirus.jhu.edu/map.html

2. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ [Internet]. 2020 May 22 [cited 2020 Jul 19];369. Available from: https://www.bmj.com/content/369/bmj.m1966

3. Living with Covid19 [Internet]. National Institute for Health Research; 2020 Oct [cited 2020 Oct 29]. Available from: https://evidence.nihr.ac.uk/themedreview/living-with-covid19/

4. 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. 2020 Aug 11;324(6):603.

5. Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020 Sep 14;585(7825):339–41.

6. Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol [Internet]. 2020 Jul 2 [cited 2020 Jul 24]; Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2768098

7. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683–90.

8. Hu Y, Li W, Gao T, Cui Y, Jin Y, Li P, et al. The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination. J Virol. 2017 15;91(8).

9. Woodruff MC, Ramonell RP, Lee FE-H, Sanz I. Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection [Internet]. Infectious Diseases (except HIV/AIDS); 2020 Oct [cited 2020 Oct 31]. Available from: http://medrxiv.org/lookup/doi/10.1101/2020.10.21.20216192