The objective of this study was to evaluate baseline total serum cortisol in covid positive patients. We therefore perfomed an 8 AM serum total cortisol in all patient positive to Covid 19 who were hospitalized in the isolation unit for Covid-19 patients. We found that the mean baseline total cortisol level was 279.5 nmol/l ± 128.7. The mean cortisol level was higher in the group with oxygen therapy versus no oxygen therapy (316.0 nmol/l ± 49.7 versus 124.54 nmol/l ± 14.9). Nine patients had patent adrenal insufficiency with serum cortisol ≤ 137.9 nmol/l. We did not find a statistically significant association between serum cortisol and oxygen therapy. In contrast, serum cortisol level was associated with patient age.
The diagnosis of adrenal insufficiency requires ACTH stimulation test which is the most specific test for the diagnosis of adrenal insufficiency. However, Covid-19 infection in itself could constitute a stimulating stress for the HPA axis by the induced inflammatory systemic response. As a preliminary study, baseline adrenal function should be assessed in all COVID + patients regardless of clinical disease status.
The technique used for the bioassay was the competitive ELISA method. Although this is not the reference method, it is easy to perform and suitable for screening. Its threshold of sensitivity is 88% and it is accessible in our context.
The socio-demographic and clinical characteristics of our study population are consistent with those found in the Wuhan cohort in China. Men are the most affected by the disease and have diabetes mellitus and hypertension as the main co-morbidities. The clinical presentation is by far dominated by asthenia and fever(6).
Males are believed to be most vulnerable to 2019-nCoV due to the greater expression of ACE receptors in men than in women. In addition, men are more susceptible to co-morbidities (hypertension, diabetes, cardiovascular disease) and therefore to severe forms of the disease(7).
Diabetes is an independent predictor of morbidity and mortality in COVID-19(8,9). Regardless of the time of discovery, it predisposes to severe forms through its susceptibility to infection. This is due to impairment of immune mechanisms, dysfunction of immune cells, oxidative stress caused by hyperglycemia and hypersecretion of counter-regulatory hormones(10). However, SARS-CoV-2 as a risk factor for glycemic dysregulation is yet to be demonstrated. Some authors have raised the hypothesis of viral colonization of the pancreas through ACE receptors expressed in islets of Langerhans, however pancreatic viral particles have not been isolated in the autopsy series(8).
The mean baseline cortisol level (279.5 nmol/l ± 128.7) with 69 patients (86.3%) with baseline cortisol ≤ 413.79 nmol/l and 09 patients with cortisol less than 137.93 nmol/l represent an insufficient adrenal response to the stress induced by 2019-nCoV infection. Tricia Tan et al. in 2020 found an association between baseline cortisol threshold value ≥ 744 nmol/l and worsening morbidity/mortality in COVID-19. They compared the value of the patient's baseline cortisolaemia within 03 days following the onset of symptoms and its fate during the following 42 days. This suggests integrity and an adapted response of the corticotropic axis in the acute phase of infection(11).
Nevertheless, these results are not applicable in our context since our patients were enrolled later in the infection (beyond 03 days). The cytokine storm characteristic of SARS-CoV-2 infection and predictor of disease severity occurs from day 6(2,12). This overly inadequate inflammatory response to viral aggression would also be incriminated in the syndrome of multivisceral failure with damage to the corticotropic axis in COVID-19 by destruction of the adrenal parenchyma(4). This suggests an alteration of the cortisolic response later in the infection. In our series, it is clear that the mean baseline cortisol level decreases with the duration of symptoms (293.3 nmol/l ± 115.2 vs 269.24 nmol/l ± 142.2).
The cortisolic response is inadequate in both the oxygen therapy group and the non-severe group. This suggests an insufficiency of basal cortisol secretion in response to stress in all phases of the disease, from less symptomatic patients to patients on respiratory assistance. During the SARS outbreak in 2003, adrenal insufficiency was described in patients infected with SARS-CoV 1(4,13,14). Three mechanisms were incriminated:
1-Necrosis of the adrenal tissue found in autopsy series by viral colonization of the adrenals through ACE receptors expressed in this tissue and the cytokine tornado triggered by the viral infection and directed to the adrenals.
2-Viral infiltration of the hypothalamo-pituitary axis through ACE receptors expressed in this tissue and resulting in hypopituitarism.
3-Corticotropic insufficiency caused by antibodies to ACTH. This is explained by the molecular analogy between viral proteins and ACTH(15).
2019-nCoV, a virus of the same family as SARS-CoV-1, could also trigger the same mechanisms and be responsible for adrenal insufficiency.
Preliminary results from the RECOVERY study published in June 2020 showed a significant reduction in mortality in severe patients with dexamethasone (10). This potent corticosteroid is believed to be effective in reducing the cytokine storm characteristic of severe and lethal forms of COVID-19. Hence the benefit of corticosteroid therapy in severe forms of the disease which will act as an anti-inflammatory and could also have a benefit in hormone supplementation if there is associated cortisol deficiency. In our cohort, there is evidence of an insufficient and inadequate cortisol response that may require supplementation for effective control of COVID-19.