Abstract
Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave (n = 35) and second wave (n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.
Highlights
We know that the clinical symptoms of the Coronavirus disease 2019 (COVID-19) infection may present with a heterogeneous clinical phenotype ranging from asymptomatic to mild [1] or severe forms [2] with pulmonary and endothelial inflammation, thromboembolic complications, acute respiratory distress syndrome (ARDS), and multi-organ failure
In the first wave we found that 5/35 (14.3%) patients died during the infection (WHO 7), while in the second wave, those who did not survive were 7/153 (4.6%)
We obobserved a significantly lower percentage of males compared to the first wave, in more served a significantly lower percentage of males compared to the first wave, in more sesevere subgroups of both the waves, the presence male patients had percenta higher vere subgroups of both the waves, the presence of maleofpatients still had still a higher percentage, indicating that for some reason the male gender relates with more severe age, indicating that for some reason the male gender relates with more severe disease [20]
Summary
We know that the clinical symptoms of the Coronavirus disease 2019(COVID-19) infection may present with a heterogeneous clinical phenotype ranging from asymptomatic to mild [1] or severe forms [2] with pulmonary and endothelial inflammation, thromboembolic complications, acute respiratory distress syndrome (ARDS), and multi-organ failure. Nitric oxide (NO) is a reactive oxygen species (ROS) known to inhibit viral replication by cytotoxic reactions that modify viral proteins and nucleic acids [7]. It contributes to the maintenance of normal endothelial function by helping arterial oxygenation and the modulation of inflammatory pathways, preventing the cytokine storm and ARDS. It has a bronchodilator effect and stimulates mucociliary clearance [8]. NO was used to treat ARDS and other diseases [9], and recently it was used to treat COVID-19 patients [10,11], among which were pregnant women with severe COVID-19 [12]
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