The present survey study investigated the prevalence of Covid-19 in a large ASD patient series from three distinct regions of Italy characterized by different pandemic spread. A significantly higher prevalence of def-sympt-Covid-19 was observed both in the whole ASD population (with respect to the Italian general population) and in the regional ASD subgroups of Tuscany, or Calabria, patients (when compared with the corresponding regional prevalence of Covid-19). The relatively low prevalence of def-sympt-Covid-19 in the Emilia Romagna might be probably associated with the lower number of ASD patients evaluated in this region compared to those from Tuscany and Calabria, and the frequent unavailability of swab test. These significant differences are reinforced by the consideration that we have compared the prevalence of symptomatic Covid-19 ASD patients, with that of Covid-19-infected patients from the general population, that comprises also about 17–20% of not symptomatic individuals (as per ISS evaluation) . In addition, the majority of subjects screened for Covid-19 were among those with high risk of infection such as health professionals. So, the differences might be more pronounced if a swab test screening would have been performed in ASD patients.
Significant differences were also found in both ASD patients with suspect-sympt-Covid-19 and in the entire group of def-sympt-Covid-19+suspect-sympt-Covid-19 ASD. Patients with suspect-sympt-Covid-19 are characterized by a number of signs and symptoms highly suggestive of Covid-19; therefore, they should be clinically considered, at least provisionally, as true Covid-19 even in the absence of oral/nasopharyngeal swabs due to limited availability of virological tests at the time of the survey.
This assumption is also suggested by the observation of two patients previously classified as suspect-sympt-Covid-19, who subsequently revealed positive at swab testing during the survey period and were therefore classified as def-sympt-Covid-19.
Of note, the patients’ awareness of the risks inherent in their chronic illness along with the frequent physical limitations, all together, may lead to very cautious patients’ lifestyle, that in the case of the ongoing pandemic has certainly reduced the risk of contracting Covid-19 measures aimed at slowing the spread of the virus. However, the statistically increased prevalence of Covid-19 observed in our large series of patients with ASD certainly related to the increased susceptibility to infections has been favored by the high exposure to the virus during the frequent contacts with medical facilities and/or hospitalizations before the restriction measures on individual movement.
The higher prevalence of Covid-19 in ASD compared to that found in Italian general population was further emphasized by some demographic observations; in particular, ASD patients showed lower mean age, as well as a higher percentage of females. These findings are in counter tendency with respect to the epidemiology of Covid-19 symptomatic patients, which are prevalently male, aged > 60 years.
Accordingly to the different diffusion of Covid-19 in the Italian territory with a clear-cut north-south gradient, the ASD patients of north-central Italian macro-area (Emilia Romagna + Tuscany) showed higher prevalence of Covid-19 than those of southern Italy (Calabria).
Previous clinical investigations focusing on patients with various ASD complicated by Covid-19 reported in the world literature are summarized in Table 4 [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33]; they include 4 single case observations [18,19,20,21], 3 cohort studies [22,23,24,25], a population-based study , and 6 survey studies [26,27,28,29,30,31, 33]. Overall, these previous reports indicated a prevalence of Covid-19 frequently comparable with those observed in the general population of corresponding geographical areas, particularly for patients series with chronic arthritis [26, 27], while increased percentage of Covid-19 affected patients with connective tissue diseases, namely systemic lupus  or large vessel vasculitis . In all cases, the ongoing immune-modifier treatments, especially bDMARD, did not affect the outcomes of symptomatic, generally mild Covid-19 disease.
Of note, the statistical analysis revealed a higher prevalence of Covid-19 in the group of patients with “connective tissue diseases”, when compared with patients affected by different “inflammatory arthritis”, possibly due to more pronounced immune system dysfunction present in the first patients’ group; in agreement with the increased prevalence of Covid-19 observed in a series of patients with systemic lupus , or large vessel vasculitis .
Another interesting finding was the higher prevalence of Covid-19 in ASD without concomitant comorbidities; this unexpected observation may deserve further investigations, and however reinforce the concept that the immune-dysfunction is the main reason of the higher prevalence of Covid-19 infection in ASD patients.
Similarly, it is very difficult to explain the increased prevalence of Covid-19 in patient without ongoing csDMARD treatments; tentatively, we can hypothesize some protective role of long-term administration of any of these medications (perhaps, hydroxyl-chloroquine) towards Covid-19 infection, while presence/absence of other immune-modulating drugs, mainly bDMARD and tsDMARD, seems to be not relevant for the development/outcome of Covid-19, in agreement with data reported in previous studies (Table 4).
Overall, the results of the present survey including a wide spectrum of ASD, i.e., “connective tissue diseases”, and “inflammatory arthritis”, seem to confirm the relatively benign outcomes of Covid-19 in patients with ASD [23,24,25,26,27,28,29,30,31], considering that only one patient with SSc complicated by lung fibrosis died among 25 subjects with def-sympt-Covid-19 or suspect-sympt-Covid-19. However, the increased prevalence of Covid-19 in ASD is in keeping with the well-known susceptibility of immune-compromised patients towards all infectious pathogens. Covid-19 is still scarcely known as regards the pathogenesis and clinical course of acute manifestations. Moreover, the few data available to now, as regards both pathological and immunological changes, are insufficient to predict the long-term effects of the infection, particularly for patients with profound immune system dysfunction such as ASD. In this respect, some manifestations of severe Covid-19 are comparable to that detectable in many ASD; in particular, the interstitial lung and diffuse vascular injury, that although evolving more quickly in severe Covid-19 disease, seems to reproduce the main pathological alterations of SSc [34, 35].
Our study may present some limitations, mainly with regards to the modality of patients’ data recording and the lack of proper virological testing in patients with highly suspected Covid-19. The limitations inherent to telemedicine, largely used during the pandemic restrictions on individual mobility, might be balanced at least in part by the good compliance of patients, interviewed by the same physicians who normally followed them in the face-to-face outpatient visits. While the classification of Covid-19 as highly suspected, on the basis of clear-cut clinical symptoms, should be confirmed by patients’ follow-up study with validated antibody tests able to detected previous exposure to Covid-19.
In conclusion, the finding of a higher prevalence of Covid-19 in immune-compromised ASD patients is particularly challenging for at least two aspects: (a) firstly, it suggests the need to develop valuable prevention and management strategies for ASD patients particularly vulnerable during the ongoing Covid-19 pandemic or its possible re-exacerbation; (b) it stimulates in-depth investigations to verify the potential interactions between Covid-19 infection and impaired immune system of ASD that may affect the natural course of both disorders.