COVID-19: New Psychiatric and Physical Understandings

Part 1: Interaction of psychological, physiological, and immunological systems.

Posted Jun 10, 2020

Coronaviruses can mutate and recombine (i.e., change), as was seen with SARS-COV in 2002 and the Middle East Respiratory Syndrome coronavirus (MERS-COV) in 2012(1). However, COVID-19 is more contagious (i.e., spreads rapidly or exponentially) between humans, principally through respiratory droplets or contact with even asymptomatic carriers. It is less lethal than SARS-COV with up to 10 percent or MERS-COV with up to 25 percent deaths, respectively. 

They all enter humans through a cell receptor called angiotensin-converting enzyme-2 (ACE-2), which is mainly involved in blood pressure regulation. It exists on the outer membranes of specific cells found in the heart, testis, lungs, kidneys, nasal mucosa, nasopharynx, stomach, skin, lymph nodes, liver, brain, etc. ACE-2 protein was found on lung alveolar epithelial cells (i.e., where air oxygen/blood vessels interface for absorption) and on enterocytes of the intestine, which are the absorptive cells lining the inner surface of the small and large intestine. Also of concern is that ACE-2 was found in the venous and arterial endothelial cells that line the blood vessels, as well as arterial smooth muscle cells in all of the organs studied (1,2), whose inflammation could contribute to clots and strokes. 

Despite the presence of SARS-COV in blood and ACE-2 on the endothelia of all organs studied, only a lesser number of organs become virus-positive (2). COVID-19 patients who were taking anti-hypertensive drugs which block ACE-2, prior to admission, had a lower mortality risk (4). Possibly, because it needs a co-receptor such as the protease TMPRSS2 to be effective (3). They are spewing virus from their nasal cavities, but the viral entry into their bodies has been blocked to a lesser or greater degree by their immune system response, possibly beginning in their nose, or actually having a lower density of receptors (ACE-2). 

Milder symptomatic outpatients have varying degrees of cough, fever, and shortness of breath but also fatigue and myalgia (5). However, a loss of taste and smell appears to occur in 71 percent and 68 percent, respectively, of patients who tested positive before any other symptoms (6). Similar results, but with six patients reporting it as their only symptom, were obtained in a telephone survey of 202 outpatients positive for COVID-19. Of these patients, 36.1 percent reported a blocked nose, 43.6 percent diarrhea, 44.6 percent muscle or joint pain, and 68.3 percent feeling tired (5). In another study, 50.5 percent of adults and 10 percent of children presented with digestive problems, including a lack of appetite, diarrhea, vomiting, and abdominal pain (7).

The psychological and emotional issues and associated factors have been reported from China among the general population and health care workers (HCW) exposed to COVID-19(8,9). In the general population, female gender, student status, specific physical symptoms, such as myalgia (muscle pain and achiness), dizziness, coryza (mucousy nasal discharge including white blood cells, which deters infection, encouraging us to clear our nose by blowing it), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and significantly higher levels of stress, anxiety, and depression(8). Another study of 1,257 HCW treating patients exposed to COVID-19 reported symptoms of depression in 634 (50.4 percent), anxiety in 560 (44.6 percent), insomnia in 427 (34.0 percent), and distress in 899 (71.5 percent)(9).

Previous studies of SARS-COV-infected survivors of the 2003 outbreak found persistent psychological symptoms(10-12). A Hong Kong study(13) of 90 SARS-COV-infected survivors, who were a well-educated, relatively young (mean age 41.1 years) group, which included 27 (30 percent) health care workers (HCW), was completed 30 months after the initial episode. In the 90 patients, no permanent lung damage was observed, but 25 percent have varying degrees of death of bone tissue due to a lack of blood supply, which raises the question of vascular blockage clotting. Nine (10 percent) of these patients had one or more family members die of SARS-COV. The cumulative incidence of psychiatric disorders during the 30 month convalescent period was 58.4 percent, with 44.4 percent diagnosed with major depressive, 47.8 percent with PTSD, 13.3 percent with panic disorder, and 6.6 percent with agoraphobia or fear of places that causes panic, helplessness, or embarrassment, such as crowds or leaving home alone. 

At the 30-month post-recovery point, major depression was 13.3 percent, PTSD was 25.6 percent, panic disorders were at 7.8 percent, and agoraphobia at 3.3 percent. Thirty percent (n=27) of the 90 patients studied were health care workers (HCW), of which 68.9 percent were married or cohabitating at the time of the SARS outbreak. One divorced, and five patient’s spouses died of SARS after the outbreak. 

During the 30-month convalescent period, the rate of unemployment increased from 3.3 to 14.4 percent, retirement from 0 to 4.4 percent, and 22 percent were on some type of sick leave, with 7.4 percent applying for early retirement. It is understandable why the authors concluded that the initial and ongoing toll of this invisible illness was a “mental health catastrophe”(13). This increased risk for PTSD (another invisible illness) in SARS patients who were HCW was supported by another study(10). HCW who were not infected but cared for SARS patients also underwent severe psychological stress and even mental illness up to two years after the outbreak(14-15)... “The experience of witnessing adverse events during hospitalization, uncertainty regarding one’s prognosis, and the need for ICU care all constituted a terrifying experience for SARS victims(13) as well as their HCW and their families.

Thus, it is not surprising that non-infected HCW (and possibly even some family members) who observed this disease treatment process feared that they would become SARS-COV victims and would also experience substantial psychological distress.

This post is Part 1 of a series. Click here to read Part 2. 


1. Murray, K. F., Gold, B. D., Shamir, R., et al: COVID-19 and the Pediatric Gastroenterologist. J. Ped. Gastroenterology Nutrition: 2020, Publish Ahead of Print doi: 10.1097/MPG.0000000000002730

2. Hamming, I., Timens, W., Bulthuis, M. L., et al: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631-7.

3. Hoffman, M., Kleine-Weber, H., Schroeder, S., et al: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052.

4. Zhang, P., Zhu, L., Cai, J., et al: Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317134.

5. Yan, C. H., Farhoud, M., Prajapati, D. P., et al: Association of Chemosensory Dysfunction and Covid-19 in Patients Presenting With Influenza-Like Symptoms J Pathol. 2004 Jun;203(2):631-7. International Forum of Allergy & Rhinology. 12 April 2020.

6. Spinato, G., Fabbris, C., Polesel, J., et al: Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 Apr 22. doi: 10.1001/jama.2020.6771.

7. Guan, W., Ni, Z., Hu, Y., et al: Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med [Epub ahead of print.] February 28, 2020; 382:1708-1720. DOI: 10.1056/NEJMoa2002032

8. Wang, C., Pan, R., Wan, X., et al: Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China. Int J Environ Res Public Health. 2020;17(5):1729. doi: 10.3390/ijerph17051729.

9. Lai, J., Ma, S., Wang, Y., et al: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020 Mar 2;3(3):e203976. doi: 10.1001/jamanetworkopen.2020.3976.

10. Lee, AM., Wong., JG., McAlonan, GM., et al: Stress and psychological distress among SARS survivors 1 year after the outbreak. Can J Psychiatry. 2007 Apr;52(4):233-40.

11. Sheng, B., Cheng, SK., Lau, KK., et al: The effects of disease severity, use of corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients at acute and convalescent phases. Eur Psychiatry. 2005 May;20(3):236-42.

12. Kwek, SK., Chew, WM., Ong, KC., et al: Quality of life and psychological status in survivors of severe acute respiratory syndrome at 3 months post discharge. J Psychosom Res. 2006 May;60(5):513-9.

13. Mak, IW., Chu, CM., Pan PC., et al: Long-term psychiatric morbidities among SARS survivors. Gen Hosp Psychiatry. 2009 Jul-Aug;31(4):318-26. doi: 10.1016/j.genhosppsych.2009.03.001. available online at

14. Maunder, RG., Lancee, WJ., Balderson, KE., et al: Long-term psychological and occupational effects of providing hospital healthcare during SARS outbreak. Emerg Infect Dis. 2006 Dec;12(12):1924-32.

15. Lancee, W. J., Maunder R. G., Goldbloom, D. S., and Coauthors for the Impact of SARS Study: Prevalence of Psychiatric Disorders Among Toronto Hospital Workers One to Two Years After the SARS Outbreak. Psychiatr Serv. 2008 Jan; 59(1): 91–95. doi: 10.1176/ps.2008.59.1.91

16. Wu, KK., Chan, SK., Ma, TM.: Posttraumatic stress, anxiety, and depression in survivors of severe acute respiratory syndrome (SARS). J Trauma Stress. 2005 Feb;18(1):39-42.