AUTHOR: SEOK WOO YANG, MD & PhD
CONTACT: E.mail: soplab@outlook.kr
DATE: 2020.03.22.
CONTENT:
Besides the acute respiratory distress syndrome in the patients affected by COVID-19, the possibility of subclinical adrenal insufficiency should be considered. When patients are lethargic and dehydrated, intravenous glucose infusion can be considered. But if patients have adrenal insufficiency, intravenous glucose infusion can cause lethal damage, as the following reasons:
Based on the genetic and clinical similarity of COVID-19 to SARS coronaviruses, the autopsy findings in SARS affected patients are helpful to expect the things to come during the disease progression.
In the autopsy of SARS cases, the adrenal glands in patients revealed necrosis, infiltration of monocytes and lymphocytes loaded with SARS coronaviruses within vessels, and thrombosis in small veins.[1][2]
With this finding, we can infer the possibility of adrenal insufficiency.
In patients with adrenal insufficiency who have not received glucocorticoids, glucose infusion may cause high fever ("glucose fever") followed by collapse and death. Presumably, the glucose is metabolized, and the water dilutes the plasma, and the resultant osmotic gradient between the plasma and the cells causes the cells of the thermoregulatory centers in the hypothalamus to swell to such an extent that their function is disrupted.[3]
The author infers that the neuropathologic change of glucose fever may be similar to that of central pontine myelinolysis after too rapid medical correction of sodium deficiency (hyponatremia). Hyponatremia is often accompanied by adrenal insufficiency. Central pontine myelinolysis causes damage to myelin and neuron in the brainstem, especially pons and even extrapontine brain tissue.
On this point, intravenous fluid therapy in COVID-19 patients, subclinical hyponatremia conditions should be also considered.
The brain tissues infected with SARS coronaviruses are supposed to be susceptible to this hypothetical neural damage.
Gu J et al summarized many reports about observations of the central nervous system affected with SARS-coronaviruses, as follows:
RT-PCR has detected SARS-CoV genomic sequences in cerebral spinal fluid and in brain tissue specimens. The virus has been successfully isolated from brain tissue. Edema and focal degeneration of neurons have been observed in the brains of SARS autopsies. IHC(immunohistochemical stain), in situ hybridization, and EM(electron microscopy) have confirmed viral infection of neurons. Gliocytes have also been found infected by SARS-coronaviruses.[4]
With the above reasons, the possibility of adrenal insufficiency and related neurologic damage can be applied to the cases with COVID-19.
For this reason, when patients with COVID-19 are lethargic and dehydrated, intravenous fluid therapy should be done without glucose except for overt hypoglycemic conditions and without rapid correction of hyponatremia.
To correct the adrenal insufficiency, the physiologic dose of steroids should be prescribed in the early phase of COVID-19. This may be also beneficial to prevent acute respiratory distress syndrome in COVID-19, for alveolar macrophages induce cytokine-related inflammatory responses that can be lessened by steroids.
P.S.
The physiologic dose of steroids the author recommends is methylprednisolone 1mg #2 (0.5mg intake two times) per day at a 60kg weighted person.
REFERENCE:
[1] Ding YQ, Wang HJ, Shen H, Li ZG, Geng J, Han HX, Cai JJ, Li X, Kang W, Weng DS, Lu YD, Wu DH, He L, Yao KT. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003;200:282–289.
[2] Gu J, Gong EC, Zhang B, Zheng J, Gao ZF, Zhong YF, Zou WZ, Zhan J, Wang SL, Xie ZG, Zhuang H, Wu BQ, Zhong HH, Shao HQ, Fang WG, Gao DX, Pei F, Li XW, He ZP, Xu DZ, Shi XY, Anderson VM, Leong ASY. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202:415–424.
[4] Gu J, Korteweg C. Pathology and Pathogenesis of Severe Acute Respiratory Syndrome. Am J Pathol. 2007 Apr; 170(4): 1136–1147.
[3] Ganong WF. Chapter 20. The Adrenal Medulla & Adrenal Cortex, In Review of Medical Physiology, 22nd ed. Appleton & Lange, 2005, p 370.