Skip to main content
Download PDF

COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series

Clinical Rheumatology volume 39, pages 3195–3204 (2020)Cite this article

Abstract

Introduction

Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic.

Method

This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test.

Results

A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to “Italian general population” (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various “connective tissue diseases” compared to “inflammatory arthritis group” (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011).

Conclusions

The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases.

Key Points
• Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients’ increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement.
• The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing.
• Patients with “connective tissue diseases” show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to “inflammatory arthritis group”.
• Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Introduction

The recent outbreak due to a newly identified β-coronavirus (Covid-19, or SARS-CoV-2) spreads worldwide (today, May 21, 2020); > 5,000,000 cases are reported, and the number is increasing every day. About 30–70% of infected patients are asymptomatic (asymptom-covid-19); however, 20–50% need hospitalization [1, 2].

Within the subset of Covid-19 symptomatic patients (sympt-Covid-19) admitted to hospital, the most common symptoms at onset of illness were fever, cough, dyspnea, myalgia, or fatigue. Notably, 20–30% of sympt-Covid-19 had upper respiratory tract symptoms such as coryza or other symptoms such as nausea, vomiting, diarrhea, dysgeusia, and anosmia. About 20–30% of hospitalized patients required intensive care unit admission for respiratory support; among them, 70–80% of patients were male, older than 65 years, and 30–50% had pre-existing comorbidities, such as hypertension (15–25%), diabetes (20–25%), obesity, and cardiovascular diseases (10–15%), or chronic obstructive pulmonary disease (10–15%) [2,3,4,5,6]. On the whole, increased risk to worse Covid-19 disease outcomes may be observed in immune-compromised patients [6,7,8,9]. Therefore, Covid-19 pandemic infection poses a serious challenge for the management of patients with “inflammatory autoimmune systemic diseases” (ASD). In fact, ASD patients represent a vast population of tens of millions of patients worldwide with compromised immune system and increased susceptibility to different types of viral and bacterial infections, frequently aggravated by ongoing immune modifier treatments [6,7,8,9].

On the other side, several anecdotal observations and cohort studies of ASD patients suggested the potential therapeutic role of some anti-rheumatic immune-modulating drugs (such as hydroxychloroquine and tocilizumab), which may potentially interfere with viral infection or the cytokine storm syndrome observed in Covid-19 in association with severe acute respiratory distress syndrome. Therefore, the immune-compromised condition along with the frequent administration of immune-suppressive treatments in ASD patients might prevent them from Covid-19 major complications [8, 10,11,12,13].

These apparently conflicting assumptions may be clarified by epidemiological studies on the actual incidence of Covid-19 in ASD patients, as well as by the results of ongoing trials on various anti-inflammatory/immune-modulating therapies in patients with Covid-19 [8, 10,11,12,13,14,15].

At the beginning of March 2020, the rapid diffusion of pandemic Covid-19 has induced the Italian government to take stringent measures aimed at slowing the spread of the virus. The restrictions on individual movement have compromised the regular face-to-face activities of outpatient clinics, mainly required for the tight monitoring of ASD patients undergoing immune-modulating treatments; the same restrictions also prevented the timely detection of symptoms suggestive of Covid-19 disease. In this context, we organized a multicenter telephone survey study aiming to identify subjects with overt/suspected Covid-19 disease in a large ASD patient population.

Here, we report the epidemiological and clinical findings, observed in our ASD patients during the 6-week survey period coincident with the most critical phase of pandemic Covid-19 in Italy.

Patients and methods

The present observational multicenter cohort study aimed to investigate the prevalence of Covid-19 infection in a large series of ASD Italian patients, resident in three geographical areas of Italy, with different prevalence of Covid-19 infection (high prevalence in north, medium in central, and low in south, Italy), by means of a telephone 6-week survey (from March 15th, to April 25th) in order to evaluate the cumulative prevalence from January 2020 of overt/suspected Covid-19 disease in ASD.

Table 1 summarizes the main characteristics of ASD patients followed at the 13 tertiary referral centers of three regions of northern (Emilia Romagna), central (Tuscany), and southern (Calabria) Italy. A total of 1641 unselected ASD patients (F 1256, M 385, mean age 59.7 ± 13.2 years, mean disease duration 11.5 ± 8.3 years) were consecutively enrolled. The classification and clinical assessment of various ASD diseases were carried out by means of current international criteria [16]. Clinical-epidemiological and laboratory features, including comorbidities (obesity, hypertension, diabetes, renal, pulmonary, and cardiovascular involvement), were obtained from individual records of ASD patients. In addition, the following information were carefully collected by trained physicians during the telephone interview according to standardized symptom-assessment questionnaire:

  1. (1)

    updating of ASD clinical features, disease activity, and ongoing treatments of underlying comorbidities;

  2. (2)

    presence and duration of any signs/symptoms [fever (temperature > 99 °F), cough, dyspnea, myalgia, arthralgia, fatigue, coryza, nausea, vomiting, headache, diarrhea, dysgeusia, anosmia] of Covid-19 disease that had appeared within the last 2 months;

  3. (3)

    sudden worsening of pre-existing manifestations such as arthralgia, myalgia, fatigue, fever, skin lesions, and respiratory symptoms (i.e., cough and dyspnea) possibly due to ASD-related interstitial lung involvement;

  4. (4)

    results (if any) of oral/nasopharyngeal swabs for Covid-19 infection at polymerase-chain-reaction testing.

Table 1 Clinico-epidemiological features and treatments of 1641 patients recruited for the survey on COVID-19 and ASD
Full size table

Subjects experiencing any symptom variations were invited to contact directly the interviewing physicians, after the call.

On these bases, Covid-19 was classified as

  1. (1)

    definite diagnosis of Covid-19 disease (def-sympt-Covid-19): presence of symptomatic Covid-19 infection always confirmed by positive oral/nasopharyngeal swabs at polymerase chain reaction testing;

  2. (2)

    highly suspected Covid-19 disease (suspect-sympt-Covid-19): presence of fever (temperature > 99 °F) and/or known contact with Covid-19-infected individual, plus four or more symptoms, such as dry cough, sore throat, shortness of breath, dyspnea, sudden worsening of preexisting respiratory symptoms, anosmia, dysgeusia, nausea, vomiting, headache, diarrhea. This group comprises a significant number of patients characterized by manifestations highly suggestive of Covid-19 disease not confirmed by Covid-19 oral/nasopharyngeal swabs at polymerase chain reaction testing (because they were not submitted to the test, often due to limited availability of virological tests).

The results were analyzed performing the odds ratio (OR) by Java-Stat 2-way Contingency Table Analysis. STATA, and StatView were also used to evaluate other variables (data are expressed as mean ± 2SD).

Shapiro-Wilk test was used to evaluate the distribution of age and disease duration.

Results

Main demographic and clinical features of the 1641 ASD Italian patients examined in this survey study are reported in Table 1. The ASD series encompasses 938 patients with “inflammatory arthritis” (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis), 615 patients with “connective tissue diseases” [systemic sclerosis (SSc), systemic lupus, undifferentiated connective tissue disease, polymyositis/dermatomyositis, Sjogren’s syndrome], and miscellany of 88 subjects with less frequent ASD. The female/male ratio (3.26:1) of the whole series confirmed the well-known prevalence of female gender commonly observed in ASD, especially in connective tissue diseases.

With respect to ongoing treatments, the large majority of patients (95%) were taking at least one of the major anti-rheumatic immune-modifier drugs, namely, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), biological disease-modifying anti-rheumatic drugs (bDMARD), and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARD). Patients with “connective tissue diseases” were more often treated with mycophenolate mofetil, methotrexate, some bDMARD (rituximab and belimumab), and/or vasoactive drugs [the latter more frequently employed in SSc patients] (Table 1), than patients with “inflammatory arthritis”.

Following the proposed classification criteria, def-sympt-Covid-19 was recorded in 11 (0.7%) and suspect-sympt-Covid-19 in 14 (0.8%) ASD patients; on the whole 25 patients with def-sympt-Covid-19, or suspect-sympt-Covid-19, were present among ASD patients (1.5%). This prevalence was higher than that observed in the Italian population of Covid-19-infected individuals [349/100,000 = 0.3%; data from the Italian Superior Institute of Health (ISS)] [17].

A lower mean age and a higher prevalence of female gender were observed in the ASD population with respect to the Italian Covid-19-infected population (60 vs 62 years; 76% vs 53%, respectively) [17].Clinically, mild-moderate Covid-19 syndrome was observed in 23 ASD patients without differences between def-sympt-Covid-19 or suspect-sympt-Covid-19. Two patients developed severe Covid-19 disease, namely: (1) a 74-year-old female with inflammatory arthritis associated to Schnitzler’s syndrome developed def-sympt-Covid-19 needing hospitalization for severe pneumonia, who recovered within a 3-week period; (2) a 65-year-old female with SSc (and lung fibrosis) with def-sympt-Covid-19, who died for severe acute respiratory distress syndrome, pulmonary venous/arterial thrombotic disease, and embolic stroke.

On the whole, significant higher prevalence of def-sympt-Covid-19 was observed in patients resident in the two regions of north-central Italy (Emilia Romagna and Tuscany), compared to southern Italy (Calabria) (p = .000).

Table 2 shows the prevalence of def-sympt-Covid-19 or suspect-sympt-Covid-19, observed in the ASD series compared to the prevalence of Covid-19 infection in the Italian, or regional, general population [17]. A significantly (p = .030) higher prevalence of def-sympt-Covid-19 was observed in the whole ASD series, compared to the Italian general population; similarly, a significantly higher prevalence was observed for either suspect-sympt-Covid-19 (p < .001) or when adding def-sympt-Covid-19 with suspect-sympt-Covid-19 (p = .001, and p = .000, respectively).

Table 2 Prevalence of COVID-19 in Italian patients with ASD compared to general and regional population
Full size table

The prevalence of Covid-19 recorded in ASD patients resident in the three Italian regions considered in our survey was also matched with that reported in the corresponding regional general populations [17]. A significantly higher prevalence was observed for def-sympt-Covid-19 in ASD patient subgroups resident in Tuscany (p = .000) and Calabria (p = .001) (with respect to the regional population), but not for Emilia Romagna (this last result likely due to the lower number of recruited patients in this region, and the frequent unavailability of swab test). A significantly higher prevalence was found for suspect-sympt-Covid-19 in ASD from Emilia Romagna (p = .000) or Calabria (p = .042). However, the prevalence of the def-sympt-Covid-19 + suspect-sympt-Covid-19 patients was significantly increased in each of the above mentioned regions in ASD patients (p < .000, for each comparison).

The comparison of Covid-19 infection, among the subgroups of ASD patients according to diagnosis (“connective tissue diseases” vs “inflammatory arthritis”), or absence/presence of major comorbidities, or different treatment categories, revealed some significant differences (Table 3):

  1. (a)

    the group of patients with “connective tissue diseases” showed higher prevalence of either suspect-sympt-Covid-19 (p < .000) or def-sympt-Covid-19 + suspect-sympt-Covid-19 (p < .000), compared to the complex of “inflammatory arthritis”;

  2. (b)

    the prevalence of def-sympt-Covid-19 was higher in ASD without major comorbidities (p = .015);

  3. (c)

    patients without csDMARD revealed significantly higher prevalence of either suspect-sympt-Covid-19 (p = .003) or def-sympt-Covid-19 + suspect-sympt-Covid-19 (p = .011).

Table 3 Comparison of Covid-19 prevalences among different subgroups of ASD patients
Full size table

Discussion

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) [17]. 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 [32], 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 [28] or large vessel vasculitis [29]. In all cases, the ongoing immune-modifier treatments, especially bDMARD, did not affect the outcomes of symptomatic, generally mild Covid-19 disease.

Table 4 Review of the literature on Covid-19 and autoimmune systemic diseases (ASD)
Full size table

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 [28], or large vessel vasculitis [29].

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.

References

  1. Xie M, Chen Q (2020) Insight into 2019 novel coronavirus - an updated intrim review and lessons from SARS-CoV and MERS-CoV. Int J Infect Dis 94:119–124. https://doi.org/10.1016/j.ijid.2020.03.071

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Antonelli A, Elia G, Ferrari SM, Foddis R, De Marco S, Cristaudo A, Fallahi P (2020) The Covid-19, epidemiology, Clinic and Prevention. Curr Genomics 21:157–160. https://doi.org/10.2174/1389202921999200427133052

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. WHO. Coronavirus disease 2019 (COVID-19) situation report – 51, 2020. Available: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10. Accessed 11 Mar 2020

  4. Lake MA (2020) What we know so far: COVID-19 current clinical knowledge and research. Clin Med (Lond) 20:124–127. https://doi.org/10.7861/clinmed.2019-coron

    Article  Google Scholar 

  5. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 323:1061. https://doi.org/10.1001/jama.2020.1585

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for Covid-19 (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382:1708–1720. https://doi.org/10.1056/nejmoa2002032

    CAS  Article  PubMed  Google Scholar 

  7. Memoli MJ, Athota R, Reed S, Czajkowski L, Bristol T, Proudfoot K, Hagey R, Voell J, Fiorentino C, Ademposi A, Shoham S, Taubenberger JK (2014) The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis 58:214–224. https://doi.org/10.1093/cid/cit725

    Article  PubMed  Google Scholar 

  8. Lu C, Li S, Liu Y (2020) Role of immunosuppressive therapy in rheumatic diseases concurrent with covid-19. Ann Rheum Dis:annrheumdis-2020-217460. https://doi.org/10.1136/annrheumdis-2020-217460

  9. Gianfrancesco MA, Hyrich KL, Gossec L, Strangfeld A, Carmona L, Mateus EF, Sufka P, Grainger R, Wallace Z, Bhana S, Sirotich E, Liew J, Hausmann JS, Costello W, Robinson P, Machado PM, Yazdany J (2020) Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries. Lancet Rheumatol 2:e250–e253. https://doi.org/10.1016/s2665-9913(20)30095-3

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mehta P, DF MA, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395:1033–1034. https://doi.org/10.1016/s0140-6736(20)30628-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. (2020) Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). (Released by National Health Commission & National Administration of Traditional Chinese Medicine on March 3, 2020). Chin Med J 133:1087–1095. https://doi.org/10.1097/cm9.0000000000000819

  12. Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia (2020) Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 43:E019. https://doi.org/10.3760/cma.j.issn.1001-0939.2020.03.009

    Article  Google Scholar 

  13. Marotto D, Sarzi-Puttini P (2020) What is the role of rheumatologists in the era of COVID-19? Autoimmun Rev 19:102539. https://doi.org/10.1016/j.autrev.2020.102539

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Ferro F, Elefante E, Baldini C, Bartoloni E, Puxeddu I, Talarico R, Mosca M, Bombardieri S (2020) COVID-19: the new challenge for rheumatologists. Clin Exp Rheumatol 38:175–180

    PubMed  Google Scholar 

  15. McGonagle D, Sharif K, O'Regan A, Bridgewood C (2020) The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 19:102537.102537. https://doi.org/10.1016/j.autrev.2020.102537

    CAS  Article  Google Scholar 

  16. Bijlsma JWJ, Hachulla E (2018) EULAR textbook on rheumatic diseases, 3rd edn. BMJ Publishing Group, United Kingdom

    Google Scholar 

  17. Riccardo F, Andrianou X, Bella A, Del Manso M, Urdiales AM, Fabiani M et al (2020) Integrated surveillance of COVID-19 in Italy (Epidemia COVID-19). Istituto Superiore di Sanità (ISS), Roma Updating April 28, 2020

    Google Scholar 

  18. Mihai C, Dobrota R, Schröder M, Garaiman A, Jordan S, Becker MO, Maurer B, Distler O (2020) 2 COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD. Ann Rheum Dis 79:668–669. https://doi.org/10.1136/annrheumdis-2020-217442

    CAS  Article  PubMed  Google Scholar 

  19. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Bradley Segal J et al (2020) COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr 10:537–540. https://doi.org/10.1542/hpeds.2020-0123

    Article  PubMed  Google Scholar 

  20. Guilpain P, Le Bihan C, Foulongne V, Taourel P, Pansu N, Maria ATJ et al (2020) Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia. Ann Rheum Dis: annrheumdis-2020-217549. https://doi.org/10.1136/annrheumdis-2020-217549

  21. Beydon M, Chevalier K, Al Tabaa O, Hamroun S, Delettre AS, Thomas M et al (2020) Myositis as a manifestation of SARS-CoV-2. Ann Rheum Dis: annrheumdis-2020-217549. https://doi.org/10.1136/annrheumdis-2020-217549

  22. Mathian A, Mahevas M, Rohmer J, Roumier M, Cohen-Aubart F, Amador-Borrero B et al (2020) Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Ann Rheum Dis: annrheumdis-2020-217875. https://doi.org/10.1136/annrheumdis-2020-217566

  23. Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly P, Neimann A, Adhikari S, Hudesman D, Scher JU (2020) Covid-19 in immune-mediated inflammatory diseases - case series from New York. N Engl J Med 383:85–88. https://doi.org/10.1056/nejmc2009567

    CAS  Article  PubMed  Google Scholar 

  24. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D'Antiga L (2020) An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395:1771–1778. https://doi.org/10.1016/s0140-6736(20)31103-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Cheng C, Li C, Zhao T, Yue J, Yang F, Yan Y, Liu X (2020) COVID-19 with rheumatic diseases: a report of 5 cases. Clin Rheumatol 14:1–5. https://doi.org/10.1007/s10067-020-05160-x

    Article  Google Scholar 

  26. Monti S, Balduzzi S, Delvino P, Bellis E, Quadrelli VS, Montecucco C (2020) Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 79:667–668. https://doi.org/10.1136/annrheumdis-2020-217424

    CAS  Article  PubMed  Google Scholar 

  27. Favalli EG, Ingegnoli F, Cimaz R, Caporali R (2020) What is the true incidence of COVID-19 in patients with rheumatic diseases? Ann Rheum Dis annrheumdis-2020-217615. https://doi.org/10.1136/annrheumdis-2020-217615

  28. Bozzalla Cassione E, Zanframundo G, Biglia A, Codullo V, Montecucco C, Cavagna L (2020) COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine. Ann Rheum Dis annrheumdis-2020-217717. https://doi.org/10.1136/annrheumdis-2020-217717

  29. Tomelleri A, Sartorelli S, Campochiaro C, Baldissera EM, Dagna L (2020) Impact of COVID-19 pandemic on patients with large-vessel vasculitis in Italy: a monocentric survey. Ann Rheum Dis: annrheumdis-2020-217600. https://doi.org/10.1136/annrheumdis-2020-217600

  30. Emmi G, Bettiol A, Mattioli I, Silvestri E, Di Scala G, Urban ML, Vaglio A, Prisco D (2020) SARS-CoV-2 infection among patients with systemic autoimmune diseases. Autoimmunity Rev 2020:102575. https://doi.org/10.1016/j.autrev.2020.102575

    CAS  Article  Google Scholar 

  31. Conticini E, Bargagli E, Bardelli M, Rana GD, Baldi C, Cameli P, Gentileschi S, Bennett D, Falsetti P, Lanzarone N, Bellisai F, Barreca C, D'Alessandro R, Cantarini L, Frediani B (2020) COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs. Ann Rheum Dis:annrheumdis-2020-217681. https://doi.org/10.1136/annrheumdis-2020-217681

  32. Quartuccio L, Valent F, Pasut E, Tascini C, De Vita S (2020) Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: a population-based study in the first two months of COVID-19 outbreak in Italy. Joint Bone Spine. https://doi.org/10.1016/j.jbspin.2020.05.003

  33. Zen M, Fuzzi E, Astorri D, Saccon F, Padoan R, Ienna L, Cozzi G, Depascale R, Zanatta E, Gasparotto M, Benvenuti F, Bindoli S, Gatto M, Felicetti M, Ortolan A, Campaniello D, Larosa M, Lorenzin M, Ramonda R, Sfriso P, Schiavon F, Iaccarino L, Doria A (2020) SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: a cross-sectional study on 916 patients. J Autoimmun 102502. https://doi.org/10.1016/j.jaut.2020.102502

  34. Matucci-Cerinic M, Bruni C, Allanore Y, Clementi M, Dagna L, Damjanov NS, de Paulis A, Denton CP, Distler O, Fox D, Furst DE, Khanna D, Krieg T, Kuwana M, Lee EB, Li M, Pillai S, Wang Y, Zeng X, Taliani G (2020) Systemic sclerosis and the COVID-19 pandemic: World Scleroderma Foundation preliminary advice for patient management. Ann Rheum Dis 79:724–726. https://doi.org/10.1136/annrheumdis-2020-217407

    CAS  Article  PubMed  Google Scholar 

  35. Del Papa N, Sambataro G, Minniti A, Pignataro F, Caporali R (2020) Novel COronaVirus disease 2019 (COVID-19) epidemic: what are the risks for systemic sclerosis patients? Autoimmun Rev 19:102558. https://doi.org/10.1016/j.autrev.2020.102558

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Open access funding provided by Università di Pisa within the CRUI-CARE Agreement.

Author information

Authors and Affiliations

  1. Rheumatology Unit, School of Medicine, University of Modena & RE, Modena, Italy

    Clodoveo Ferri, Dilia Giuggioli & Amelia Spinella

  2. Rheumatology Clinic ‘Madonna dello Scoglio’ Cotronei, Crotone, Italy

    Clodoveo Ferri, Vincenzo Raimondo, Raffaele Brittelli, Vincenzo Aiello & Rodolfo Caminiti

  3. Rheumatology Outpatient Clinic, ASP-Vibo Valentia–Tropea Hospital, Tropea, Italy

    Massimo L’Andolina

  4. Clinical Immunology Unit, University of Pisa, Pisa, Italy

    Antonio Tavoni, Silvia Bilia & Daiana Giannini

  5. Ospedale di Portoferraio, Livorno, Italy

    Riccardo Cecchetti

  6. Rheumatology Unit, University of Florence, Florence, Italy

    Serena Guiducci & Silvia Bellando-Randone

  7. Rizzoli Orthopaedic Institute Bologna, University of Bologna, Bologna, Italy

    Francesco Ursini, Veronica Brusi & Riccardo Meliconi

  8. UOD Reumatologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy

    Maurizio Caminiti & Giuseppa Pagano Mariano

  9. U.O.S. Reumatologia, Ospedale Castrovillari, Cosenza, Italy

    Giuseppe Varcasia & Tommaso Ferrari

  10. U.O.T. Specialistica Ambulatoriale ASP 201, Cosenza, Italy

    Pietro Gigliotti

  11. U.O.C. Medicina Interna “M.Valentini” P.O. Annunziata, Cosenza, Italy

    Roberta Pellegrini

  12. Rheumatology Outpatient Clinic, San Giovanni di Dio Hospital, Crotone, Italy

    Domenico Olivo

  13. Rheumatology Unit, University of Catania, Catania, Italy

    Michele Colaci

  14. Department of Internal Medicine, San Martino Policlinic Hospital, University of Genoa, Genoa, Italy

    Giuseppe Murdaca

  15. Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy

    Poupak Fallahi

  16. Department of Clinical and Experimental Medicine, Immuno-Endocrine Section of Internal Medicine, Laboratory of Primary Human Cells, School of Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa, Italy

    Alessandro Antonelli

Authors
  1. Clodoveo Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dilia Giuggioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Raimondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo L’Andolina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Tavoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Riccardo Cecchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Serena Guiducci
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francesco Ursini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maurizio Caminiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giuseppe Varcasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pietro Gigliotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Roberta Pellegrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Domenico Olivo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Michele Colaci
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Giuseppe Murdaca
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Raffaele Brittelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Giuseppa Pagano Mariano
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Amelia Spinella
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Silvia Bellando-Randone
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Vincenzo Aiello
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Silvia Bilia
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Daiana Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Tommaso Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Rodolfo Caminiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Veronica Brusi
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Riccardo Meliconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Poupak Fallahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Alessandro Antonelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the COVID-19 & ASD Italian Study Group

Corresponding authors

Correspondence to Clodoveo Ferri or Alessandro Antonelli.

Ethics declarations

Disclosures

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ferri, C., Giuggioli, D., Raimondo, V. et al. COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series. Clin Rheumatol 39, 3195–3204 (2020). https://doi.org/10.1007/s10067-020-05334-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05334-7

Keywords

  • Arthritis
  • Autoimmune systemic diseases
  • Connective tissue diseases
  • COVID-19
  • Rheumatic diseases
  • SARS-CoV-2