Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

First 'close encounters' of post-COVID patients after mildly symptomatic COVID-19

Background: COVID-19 patients frequently report residual symptoms after SARS-CoV-2 disappearance. However, the clinical post-COVID course of patients after mildly symptomatic COVID-19 is poorly known. We addressed this question because of our current clinical involvement in COVID-19 [1] and opening of a dedicated post-COVID19 outpatient clinic at 1, 3, 6, and 12 months after recovery. Materials and Methods: We enrolled 61 patients (26 males, age range 21-79 years) after a mild SARS-CoV-2 infection (i.e., no hospitalization, home quarantine, n = 48, or hospitalization to internal medicine/pneumology units for mild pneumonia, n = 13). The presence of 20 symptoms (dyspnea, fatigue, anxiety/depression, myalgia, memory impairment, chest pain, insomnia, joint pain, concentration impairment, cough, anosmia, headache, sicca syndrome, rhinitis, dysgeusia, alopecia, diarrhea, loss of appetite, dizziness, sweating, fever) was assessed semi-quantitatively by questionnaires before COVID-19, and 1 (n = 24), 3 (n = 29) or 6 months (n = 8 subjects) after recovery confirmed by two negative and consecutive nasopharyngeal swabs. Results: The prevalence of a cluster of six residual symptoms was higher after 1 month, than before infection: dyspnea (50% vs. 0%, respectively, P = 0.0001), fatigue (41.7% vs. 8.2%, p = 0.0002), myalgia (33.3% vs. 3.3%, p = 0.0001), memory impairment (33.3% vs. 13.1%, p = 0.03), insomnia (29.1% vs. 4.9%, p = 0.02), joint pain (25% vs. 8.2%, p = 0.03). The frequency of four of these symptoms was still higher after 3 months (dyspnea 24.5%, fatigue 58.6%, myalgia 31%, memory impairment 48.2% of cases;p < 0.03 in all cases vs. before infection). At this time, we observed an increased prevalence of concentration impairment (41.4% vs. 25% before infection, p = 0.001) and headache (24.1% vs. 6.6% before infection, p = 0.01). After 6 months all symptoms disappeared, except than fatigue (25%), memory impairment (12.5%) and headache (12.5%). Conclusions: A post-COVID syndrome occurs also in subjects with prior mild disease, and symptoms last 1-6 months after viral recovery. The prevalence of fatigue and neuropsychological symptoms, in particular, is still high after 6 months and should require support to improve public quality of life.

Ongoing COVID-19 vaccination in Italy. Online survey of gender- and age-related side effects

Background: Evidences suggest that gender may influence the response to various vaccines in terms of immune response and side effects. Whether similar differences also occur with COVID-19 vaccine, is still uncertain. Materials and Methods: In March 2021, we advertised a short anonymous questionnaire (Google forms) to medical doctors, nurses, postgraduates, students and general public, consisting of 30 questions exploring 16 possible side effects (local pain or hardness, swelling, redness, allergic reaction, tiredness, headache, sleep disorders, myalgia, fever, enlarged lymph nodes, irritability, diarrhea, urticaria, vomiting, anaphylaxis). We recorded side effects after 1st dose, and within one week after 2nd dose. Data were analyzed according to gender and seven age groups. Results: We received 1,034 questionnaires from all over Italy (369 males, 665 females, age range 20-83 years). Injected vaccines were Pfizer-BioNTech (96.9%), Astra-Zeneca (2.4%), Moderna (0.7%). Major adverse events were absent. Minor adverse events occurred with both 1st dose (76.0%) and 2nd dose (78.0%) and were invariably higher in females than in males (1st dose: 79.4% vs 69.9% p = 0.0006;2nd dose: 81.8% vs 70.7%, p = 0.00004). The significant cluster of adverse events were local pain, redness, hardness at the injection site, fever, sleep disturbances, headache, lymph nodes enlargement following both doses (0.00001 < p < 0.02). Effects disappeared within 48hrs in 80% of cases (range 1-7 days). The gender difference was confirmed in the age class 30-39 after 1st dose (85.8% vs 70%, in females and males, respectively p = 0.03), and in the age classes 30-39 (84.6% vs 75.5%, in females and males, respectively p = 0.03) and 40-49 (74.8% vs 57.9%, in females and males, respectively p = 0.02) after 2nd dose. Fever tended to be more frequent in females after the 1st dose (6.5% vs 3.8%) and became significantly higher after the 2nd dose (32.9% vs 17.3%, p = 0.00001). After 50 years of age, the rate of all the recorded adverse events was similar between genders. Conclusions: COVID-19 vaccines generate frequent, although mild side effects with a gender (female) prevalence, especially in the age range 30-49 years. The gender difference disappears after 50 years of age, thus pointing to possible involvement of sex hormones and attenuated immune response.