Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy
Biagio Pinchera
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy
Annunziata De Rosa
Dipartimento di Malattie Infettive e Emergenze Infettive, Divisione di Malattie Infettive Respiratorie, Ospedale Cotugno, AORN dei Colli, 80131 Naples, Italy
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy
Mauro Mormile
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy
Gabriella Fabbrocini
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy
Roberto Parrella
Dipartimento di Malattie Infettive e Emergenze Infettive, Divisione di Malattie Infettive Respiratorie, Ospedale Cotugno, AORN dei Colli, 80131 Naples, Italy
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.