Abstract:
New-onset DM or unmasking existing one, with or without metabolic
complications, has been reported in SARS CoV-2 infection. New-onset DM
in association with HHS alone or combination with DKA is uncommon but a
possible manifestation of SARS CoV-2 infection that poses management
challenges where the outcome may be worst.
Keywords : COVID-19, SARS CoV-2, Infection, Diabetes Mellitus,
HHS, DKA.
Introduction :
The ongoing pandemic of COVID -19, which started in Wuhan, China, in
late December 2019, affects millions worldwide so far. As of November
22, 2020, over 58 million people infected over 191
countries/regions1 caused by severe acute respiratory
syndrome coronavirus-2 (SARS CoV-2).
The more vulnerable individuals are aged, with comorbid conditions like
diabetes, hypertension, obesity, and low
immunity2,3,4. SARS CoV-2 may have a diabetogenic
effect probably by direct β-cell damage that not only worsens
pre-existing diabetes but probably accelerate pre-diabetes to
established one. Yang et al. explained the β-cell damage mediated by
SARS CoV, a virus of the same family causing insulin-dependent diabetes
mellitus as β-cells carry angiotensin-converting enzyme 2 (ACE2)
expression5. SARS CoV-2 binds and enters human cells
via ACE2, a transmembrane glycoprotein6 that may
dysregulate β-cell function and consequently diabetes.
Herein we report a SAR CoV-2 positive patient with HHS and new-onset
diabetes mellitus (DM) with a fatal outcome.
Case Presentation :
A 46-year-old male, a teacher by profession, presented to the emergency
department with a history of fever, cough, shortness of breath, and
irritability for the last week. By inquiring, the patient gives a
history of increased thirst and urination for one week. There was no
history of any medical illness and within normal ranged laboratory
workup during annual screening a month ago. Clinical evolution of the
patient shows an ill-looking middle-aged dehydrated irritable patient
with a BMI of 27, vitals; fever, 39C0 pulse, 91/min,
respiratory rate, 28/min, blood pressure (BP), 105/70mmHg,
SPO2 94% on 5lit oxygen on nasal cannula and decreased
air entry in the right lung.
Initial laboratory workup shows, blood sugar level, 36.5mmol, pH 7.4,
Na+ 133mmol/dL, K+ 4.1 mmol/dL,
Cl- 78 mmol/dL,
HCO3- 29 mmol/dL, Creatinine
2.15mg/dL, BUN 52mg/dL, and serum osmolality 329mOsmol/kg, HbA1c,
87mmol/mol. and urine sample was negative for ketones. The patient was
managed in ED as per protocol and admitted in intermediate care. Due to
the ongoing COVID-19 pandemic and signs & symptoms suggestive of SARS
CoV-2 infection, RT-PCR was requested and came positive a day after. The
next day patient’s conscious level deteriorated and SPO2dropped to 90%, thus shifted to the intensive care unit (ICU) and put
on mechanical ventilation. On the fifth admission day, the patient’s
SPO2 dropped to 84% followed by the arrest that was
managed by the resuscitation team but unfortunately the patient not was
revived.
Discussion :
A well-documented factor that precipitates diabetes complications in
known or new-onset diabetes is infection. It is not apparent that
diabetes mellitus increases the chance of SARS CoV-2 infection, however,
it is evident that the outcome of COVID-19 is severe in patients with
diabetes mellitus7.
COVID -19 and diabetes have a two-way relationship. On one hand,
diabetes mellitus relates to more severe COVID -19 through exaggerated
pro-inflammatory cytokine response and a downregulated ACE2 levels along
with compromised innate immunity in addition to the use of
angiotensin-converting enzyme inhibitors and angiotensin-receptor
blockers (ACEi/ARBS). On the other hand, COVID -19 worsens the control
of glues in diabetic patients probably by direct virus-induced β-cell
damage, insulin resistance, and indirectly via
medications8.
There are reports of new-onset diabetes in patients with SARS CoV-2
confirmed infections. Tim et al9. report a young
German boy with new-onset type 1 diabetes mellitus presented with DKA,
and a patient with similar findings by Hadil et al10.
in a healthy middle-aged man. A case series of three new-onset diabetes
in SARS CoV-2 infected patients by Thirunavukkarasu
et.al11. with the possibility of unmasking existing
diabetes rather than new-onset.
The complication of diabetes, such as HHS alone or in combination with
DKA, is seen in patients with SARS coV-2 infection. In a case series of
six male patients by Chan et al., all patients have an initial
presentation of DKA & HHS together with fatal outcome in
four12. In a recent review by Pal et
al.,13 10% of the patients have new-onset diabetes
mellitus, with 83% of patients have isolated DKA and 17% as combined
DKA/HHS with male predominance, where mortality is even higher in the
latter than the first as 50%.
There are reports of new-onset diabetes mellitus with or without
complications in SARS CoV-2 infected individuals. In a retrospective
case series of 35 hospitalized hyperglycemic emergencies in SARS CoV-2
infected patients, isolated DKA was (31.4%), mixed DKA & HHS (37.1%),
hyperglycemic ketosis (25.7%), and HHS alone in two African patients
(5.7%). Only two patients were having new-onset diabetes mellitus, one
each for DKA & HHS and HSS alone14.
Un-masking pre-existing diabetes or the development of new-onset
diabetes mellitus with accompanying complications like HHS is a possible
complication of SARS CoV-2 infection that carries a high mortality. To
the best of our knowledge, only one COVID-19 patient with new-onset
diabetes mellitus & HHS, been reported in the published literature. Our
case is the second reported case with a complication of HHS in a newly
diagnosed diabetes mellitus in a SARS CoV-2 infected patient.
Conclusion :
Isolated HHS with new-onset diabetes is an unusual but possible
complication of SARS CoV-2 infection. SARS CoV-2 infection may trigger
β-cell damage in previously healthy individuals resulting in new-onset
diabetes that may present as hyperglycemic hyperosmolar state alone or
in combination with ketoacidosis where the outcome may be worst. Such
patients should be managed under close observation with established
protocols.
Key Clinical Message :
SARS CoV-2 infection may cause new-onset diabetes mellitus with or
without complications such as HHS, which carries the worst prognosis
that necessitates specific recommendations and protocols to manage such
worst complications in a better way.