4.1. Is MetHb Increased in COVID-19 Patients?
According to the case reports of Kuipers et al. [17], Al-Aamri et al. [23], Palmer et al. [22], Faisal et al. [20], and Naymagon et al. [18], MetHb values for COVID-19 patients were above the reference range of 0.67 ± 0.33% for healthy non-smokers (Borland et al. 1985) with the highest MetHb value of >30% for a patient reported by Naymagon et al. [18].
In the case reports of Palmer et al. [22], Faisal et al. [20] and Naymagon et al. [18], MetHb increased in the COVID-19 patients during the course of the disease. Data of multiple MetHb measurements during the disease course were published by Palmer et al. [22], showing a rise of MetHb to a peak after a few days and a decline after treatment (Figure 3d).
COVID-19 patients (n = 25) were shown to have a higher MetHb compared to healthy individuals (n = 25) as demonstrated in a cross-sectional study by Alamdari et al. [21], supporting the findings reported. However, the cross-sectional study of Soltan et al. [19] with a large cohort (534 COVID-19 patients and 114,957 pre-pandemic controls) showed no statistically significant differences in the MetHb values despite the fact that MetHb was an important parameter for the prediction of COVID-19 based on the algorithm the group developed. This apparent discrepancy between the result of Alamdari et al. and Soltan et al. seems to be due to the following reason: the MetHb data used by Soltan et al. stem from the time of emergency presentations and admission to hospital, whereas the MetHb data from Alamdari et al. were collected from the whole time-course of the hospital stay. Since MetHb has been reported to increase during the development of the disease [18,20,22], the results of Soltan et al. are understandable since, during the MetHb sampling time at the beginning of the disease, MetHb is not necessarily increased (at least at the group level).
In conclusion, MetHb seems to be elevated in COVID-19 patients, with a dynamic following the disease progression.