The development of ketoacidosis or hyperosmolar hyper glycemic state has a pathophysiological basis, evidenced by the relationship already identified between the reninangiotensin-aldosterone system (RAAS) and SARS-Co-V2. In addition to being expressed in the lung, angiotensin-con verting enzyme 2 (ACE2), it is also found in the pancreas¹.

We want to share our single-center observation of five patients with COVID-19 admitted for new-onset diabetic ketoacidosis (DKA), that is, with non-known history of diabetes mellitus (DM). It is well known that acute hyper glycemic crises are significantly related to morbidity and mortality in people with diabetes².

All patients were diagnosed with COVID-19 by RT-PCR technique and radiological findings. DKA was diagnosed according to the ADA 2021 criteria³, with pH < 7.3, bi carbonate < 18 mEq/l, glucose > 250 mg/dl, anion gap > 10 mEq/l and ketonemia.

The mean age was 39 years (between 28 - 57 years); four patients were overweight or obese; three died dur ing hospitalization. For risk staging, we used COVID GRAM that classified four patients at intermediate risk of progression to invasive mechanical ventilation, and ABC-GOALS (validated in the Mexican population), which ranked the same four patients with a high risk of admis sion to the intensive care unit. Demographic and clinical data of these five patients with DKA and COVID-19 are presented in Table 1.

Table 1 Demographic and clinical data of five patients with DKA and COVID-19 

A diabetogenic effect induced by the SARS CoV2 virus has been postulated. It consists of the expression of the ACE2 in the pancreas, which causes damage to the beta-pancreatic cell. The metabolic effects are added to these mechanisms, and that results from the pro-inflammatory state triggered by the viral infection, that is related to the production of IL-6 and other cytokines, the increase in the synthesis of counter-regulatory hormones such as gluca gon, catecholamines, cortisol, and the increase in critical metabolic disorders in the development of hyperglycemia (glycogenolysis and gluconeogenesis).

In our case series, the mean age was 39 years. Young adults with beta-cell functionality and nega tive autoimmunity markers are considered part of the clinical spectrum of type 2 diabetes prone to ketosis, a subgroup increasingly identified and possibly the most common phenotype in patients with ketosis. In contrast, other studies have reported the diagnosis of ketoacido sis in overweight and obese patients over 50 years of age, with higher insulin requirements and longer time to resolution of ketosis⁴.

All the patients developed acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventila tion. The two patients who required FiO₂ less than 40% could go home. We hypothesized that, regardless of the severity of ketoacidosis, the seriousness of SARS-Co-V2 pneumonia could have a greater weight in the prognosis of these patients.

The mean number of days of hospitalization was 11.6 days; the most serious case died two days after admis sion. The most prolonged hospitalization was 27 days and ended in death. In the analysis of the laboratory studies, we documented a significant variability of biomarkers. The D-dimer range was between 160-1917 ng/ml and ferritin between 223-1200 ng/ml. Procalcitonin was positive on admission in 3 patients in whom nosocomial pneumonia was diagnosed.

The two patients in invasive mechanical ventilation (IMV) had serum albumin less than 2.5 g/dl; hypoalbu minemia is a poor prognosis in patients with ARDS due to SARS-Co-V2⁵. The most severe case was a patient who did not presented lymphopenia, and a lactic dehydroge nase (DHL) of 804 mg/dl, so the clinical behavior may not be as expected in all cases. Only one of them presented myocardial damage with an elevation of troponin and brain natriuretic peptide (BNP); its outcome was death. Myocardial injury in COVID 19 is found in 6-20%. Its pres ence increases mortality to more than 50%⁶.

The HbA1C range was between 8.9-14.0%, represent ing a significant prior glycemic loss, as it has been reported in Hispanic patients; the most crucial difference was the main difference at the time of diagnosis⁷. It is important to notice that the delay in diagnosis and treatment worsens the prognosis in adults.

We acknowledge that hospitalized patients have independent risk factors for developing KDA, especially when starting to receive parenteral steroids. New-onset KDA is more common in those with BMI < 25 kg/m², HbA1C > 8.3%, and IL-6 levels > 50.9 pg/ml. As we described, obese and overweight patients are the ones who most frequently debut with DKA-COVID-19, so this association should be seriously considered, and studied in more detail.