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Hypothesis to explain the severe form of COVID-19 in Northern Italy
  1. Luca Cegolon1,2,
  2. Jennifer Pichierri3,
  3. Giuseppe Mastrangelo4,
  4. Sandro Cinquetti1,
  5. Giovanni Sotgiu5,
  6. Saverio Bellizzi6,
  7. Giuseppe Pichierri7
  1. 1Public Health Department, Local Health Unit N. 2 "Marca Trevigiana", Treviso, Veneto Region, Italy
  2. 2IRCCS Materno Infantile Burlo Garofolo, Trieste, Friuli-Venezia Giulia Region, Italy
  3. 3Children and Young People’s Diabetes, University College London Hospitals NHS Foundation Trust, London, UK
  4. 4Cardiac, Thoracic and Vascular Sciences, Padua University Hospital, Padua, Veneto Region, Italy
  5. 5Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Sardinia Region, Italy
  6. 6Partnership for Maternal, Newborn and Child Health, World Health Organization, Geneve, Switzerland
  7. 7Microbiology Department, Kingston Hospital NHS Foundation Trust, Kingston upon Thames, London, UK
  1. Correspondence to Dr Luca Cegolon; l.cegolon{at}

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What is already known about this subject?

  • Human coronaviruses are known to cause respiratory re-infections, regardless of pre-existing humoural immunity.

  • There is evidence suggesting that severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) had been circulating in Italy before the first COVID-19 case was detected in the country.

What are the new findings?

  • Prior infections with SARS-CoV-2 (or other viruses/coronaviruses) may arguably predispose to more severe forms of the disease following re-infection with SARS-CoV-2, with an immunological mechanism known as Antibody-Dependent-Enhancement, already observed with infections sustained by other coronaviruses (MERS-CoV and SARS-CoV) or other viruses such as the West Nile Virus and Dengue.

What are the recommendations for policy and practice?

  • If confirmed by in vivo studies, this hypothesis may have relevant implications for the treatment of severe forms of COVID-19, yet the possibility to produce an effective vaccine against SARS-CoV-2 might be hampered.

The ongoing COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has affected 212 countries worldwide at various degrees as of 8 May 2020.1

In this paper we discuss a hypothesis that prior viral infections—either by SARS-CoV-2 or different strains of coronaviruses, or potentially even other respiratory viruses—may predispose to more severe forms of COVID-19, following a secondary infection with SARS-CoV-2.

Most COVID-19 infections are asymptomatic or manifest with mild to moderate respiratory symptoms (fever, cough, sore throat, myalgia, fatigue and even non-severe pneumonia). Of patients with COVID-19, 14%–15% develop severe pneumonia and 5%–6% a critical condition requiring admission to intensive care unit (ICU).2–4 Death may eventually occur after an average of 17.8 days since the onset of symptoms.5

Among all countries, Italy (which was the first European COVID-19 cluster) presents a critical disease pattern as of 8 May 2020, having the third highest number of COVID-19 cases in the world after the USA and Spain, the fourth highest prevalence of the disease after Spain, Belgium and the …

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