COVID-19 has been retrospectively diagnosed in a man treated in an intensive care unit (ICU) near Paris after coughing up blood on Dec 27, 2019—4 days before the novel coronavirus cluster was identified in Wuhan, China.
This finding, published this week in the International Journal of Antimicrobial Agents, suggests that the coronavirus was already circulating undetected in France well before the first cases were reported there on Jan 24 in two returned travelers from Wuhan.
Signs, symptoms likely led to flu misdiagnosis
Suspecting that COVID-19 cases may have been mistaken for the flu, which causes similar signs and symptoms, the researchers reviewed medical records of ICU patients hospitalized with flu symptoms from Dec 2, 2019, to Jan 16 who had a negative reverse transcription-polymerase chain reaction (RT-PCR) result for the novel coronavirus on admission.
From Apr 6 to 9, they also performed RT-PCR on the frozen respiratory samples of patients who had fever, cough, runny nose, sore throat or muscle pain, and chest computed tomography (CT) findings consistent with COVID-19. The samples were available because the hospital stores all respiratory samples for 4 years in case they are later needed for research.
Fourteen of 58 patients (14%) hospitalized for flu during the study period were included in the analysis. One sample, from a 42-year-old fish seller born in Algeria who had lived in France for many years, tested positive. His most recent trip to Algeria was in August 2019, and one of his children had flu symptoms before the man became ill.
The man, who had asthma and type 2 diabetes, was coughing up blood and had headache and fever when he arrived at the hospital. He had felt ill for 4 days. CT revealed fluid buildup in both lungs, and he had low levels of lymphocytes (white blood cells important to immune response) and high levels of C-reactive protein (indicating heart damage) and fibrinogen (indicating blood clots).
A sputum sample was unremarkable, and the man was treated with antibiotics and released from the hospital on Dec 29.
A dramatically different transmission scenario possible
The authors said that the finding suggest that the actual numbers of COVID-19 infections in France may be underestimated and supports the assumption that about 18% to 23% of people infected with SARS-CoV-2, the virus that causes COVID-19, were asymptomatic The findings also support that roughly 55% of infections were caused by unidentified people, "suggesting that many asymptomatic patients were not diagnosed during January 2020 and contributed to the spread of this epidemic."
The investigators noted that the findings, along with the man's lack of a link to China or recent travel, upends current beliefs about the epidemiology of the pandemic. "It also means that several models used to predict the evolution and outcomes of the SARS-CoV-2 propagation might be based on biased data and would need to be adjusted to the actual profile of the epidemic," they said.
However, Reuters and other news outlets are reporting that the man's wife, who did not become ill, works in retail near a Paris airport frequented by international travelers.
The authors noted that they may have missed some coronavirus cases because RT-PCR can produce false-negative results, freezing may have damaged the quality of the samples, lab contamination may have occurred, and they limited the analysis to ICU patients who had symptoms and CT findings consistent with COVID-19, while most patients have mild symptoms.
They called for further analysis to pinpoint when the virus arrived in France, determine the scope of transmission, and identify any deaths that may have been mistakenly attributed to causes other than COVID-19 before the outbreak was identified.
France has reported the fifth-highest number of coronavirus cases in the world, at 169,583, with 25,204 deaths, according to the Johns Hopkins University online tracker.
Other countries have reported evidence of earlier COVID-19 spread than was at first recognized. Recently, a post-mortem examination in California showed that the first related US death occurred several weeks earlier than previously thought.