The association between acid-base status and clinical outcome in critically ill COVID-19 patients admitted to intensive care unit with an emphasis on high anion gap metabolic acidosis.

OBJECTIVE: The aim of this study was to identify arterial blood gas (ABG) abnormalities, with a focus on a high anion gap (AG) metabolic acidosis and evaluate outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU. METHODS: A retrospective, observational study was conducted in a tertiary hospital in Cape Town during the first and second COVID-19 waves. Age, gender, sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3std), pH, partial pressure of carbon dioxide (pCO2), creatinine, estimated glomerular filtration rate (eGFR), lactate levels and ABG results were obtained. The Pearson χ2 test or Fisher exact test and the Wilcoxon rank-sum test were used to compare mortality and survival. To identify factors associated with non-survival, a multivariable model was developed. RESULTS: This study included 465 patients, 226 (48%) of whom were female. The sample population's median (IQR) age was 54.2 (46.1-61.3) years, and 63% of the patients died. ABG analyses found that 283 (61%) of the 465 patients had alkalosis (pH ≥ 7.45), 65 (14%) had acidosis (pH ≤ 7.35) and 117 (25%) had normal pH (7.35-7.45). In the group with alkalosis, 199 (70.3%) had a metabolic alkalosis and in the group with acidosis, 42 (64%) had a metabolic acidosis with an increased AG of more than 17. Non-survivors were older than survivors (56.4 years versus 50.3 years, p < .001). CONCLUSION: Most of the COVID-19 patients admitted to the ICU had an alkalosis, and those with acidosis had a much worse prognosis. Higher AG metabolic acidosis was not associated with patients' characteristics.

Correlating arterial blood gas, acid-base and blood pressure abnormalities with outcomes in COVID-19 intensive care patients.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), many studies have investigated laboratory biomarkers in management and prognostication of COVID-19 patients, however to date, few have investigated arterial blood gas, acid-base and blood pressure patterns. The aim of the study is to assess the arterial blood gas and acid-base patterns, blood pressure findings and their association with the outcomes of COVID-19 patients admitted to an intensive care unit. METHODS: A single-centre retrospective, observational study in a dedicated COVID-19 intensive care unit in Cape Town, South Africa. Admission arterial blood gas, serum electrolytes, renal function and blood pressure readings performed on COVID-19 patients admitted between 26 March and 2 June 2020 were analysed and compared between survivors and non-survivors. RESULTS: A total of 56 intensive care unit patients had admission arterial blood gas performed at the time of intensive care unit admission. An alkalaemia (pH > 7.45) was observed in 36 (64.3%) patients. A higher arterial pH (median 7.48 [interquartile range: 7.45-7.51] versus 7.46 [interquartile range: 7.40-7.48], P = 0.049) and partial pressure of oxygen in arterial blood (median 7.9 kPa [interquartile range: 7.3-9.6] versus 6.5 kPa [interquartile range: 5.2-7.3], P = <0.001) were significantly associated with survival. Survivors also tended to have a higher systolic blood pressure (median: 144 mmHg [interquartile range: 134-152] versus 139 mmHg [interquartile range: 125-142], P = 0.078) and higher arterial HCO3 (median: 28.0 mmol/L [interquartile range: 25.7-28.8] versus 26.3 mmol/L [interquartile range: 24.3-27.9], P = 0.059). CONCLUSIONS: The majority of the study population admitted to intensive care unit had an alkalaemia on arterial blood gas. A higher pH and lower partial pressure of oxygen in arterial blood on arterial blood gas analysis were significantly associated with survival.

Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2).

The renin-angiotensin system is mainly associated with the regulation of blood pressure, but recently many other functions of this system have been described. ACE2, an 805-amino acid monocarboxypeptidase type I transmembrane glycoprotein, was discovered in 2000 and has sequence similarity to two other proteins, namely ACE and collectrin. The ACE2 gene is located on Xp22 and is highly polymorphic. ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract. Animal studies have found that ACE2 is central in diseases affecting almost all organ systems, among other cardiac, respiratory, renal and endocrine functions. ACE2 was identified as the cellular contact point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the global pandemic (COVID-19), and is a potential drug target. SARS-CoV-2 infection has several effects on the renin-angiotensin system and conversely, regulation of this receptor may affect the progress of infection. We describe the genetics and functions of ACE2, explore its various physiological functions in the renin-angiotensin system and discuss its role in the pathophysiology of disease. ACE2 opposes the vasopressor ACE pathway of the renin-angiotensin system by converting angiotensin (Ang) I to Ang (1-9) and Ang II to Ang (1-7) which initiates the vasodilatory pathway. ACE2 may have a protective effect in the lung and kidney as knockout mice display susceptibility to acute respiratory distress and hypertensive nephropathy. Binding of SARS-CoV-2 and the subsequent fusion and downregulation of this pathway during SARS-CoV-2 infection may explain some of the unusual sequelae seen in COVID-19.

Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2).

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in 'lockdown', social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.