Despite a growing understanding of coronavirus disease 2019 (COVID-19), more evidence is needed for successful continued prevention and treatment of infections, according to a viewpoint published in JAMA
A trio of authors from Yale School Medicine, University of Michigan, and Emory University School of Medicine examined the case fatality and outlined new clinical and epidemiological insights surrounding COVID-19. As of their writing on April 2, the total number of COVID-19-associated deaths has been more than 5000 and a global total of infections has surpassed 1 million. The United States currently has the largest number of reported cases, about 20% of all reported infections, they wrote. There are clusters of outbreaks in New York, Washington, and California; however, they added, the true number of cases is likely much higher because of challenges faced in testing capacities and restrictive case definitions.
“With community transmission firmly established, the US epidemic enters the exponential growth phase in which the number of new cases is proportional to the existing number of cases,” the authors said. “This phase continues until either enough susceptible individuals become immune as a result of infection, stringent public health measures are followed, or both.”
The case fatality rate, or the percentage of deaths among all cases, is still unknown, the authors said. The global mortality rate for COVID-19 is estimated at 4.7% but is wide-ranging: from 10.8% in Italy to as low as 0.7% in Germany. In Wuhan, China – the first epicenter of the outbreak – the case fatality rate was reported to be 5.8%.
Of the US’ first 140,904 cases, 1.7% have died, the authors said. They wrote that this is likely not a reliable case fatality rate estimate, though. As the US climbs towards the apex of COVID-19 infection, surge capacity in hospitals will influence case fatality rate.
“To have reliable estimates, better approximations of the overall population (denominator) are essential, and methods such as serosurveys using statistical sampling generalizable to the populations of interest will inform these estimates,” they said.
As new research and evidence have emerged, the importance of the data cannot be understated. The authors dissected several key questions that still remain and highlighted the importance of continued investigations.
“Is PCR Always Positive? What Is the Meaning of a Negative PCR?”
There are several types of tests being used to identify positive COVID-19 patients, they wrote, but these tests fall into 2 major categories: polymerase chain reaction (PCR)-based tests and serological testing. While PCR-based tests are the primary method for identifying COVID-19 in clinical settings, the sensitivity and specificity of diagnostic testing is unknown without any reference standard for the infection. A negative test from a PCR-based test should not exclude COVID-19, they added, because it is likely that lower respiratory samples are more sensitive than a nasopharyngeal swab. As more serological tests are developed—and more are being developed—clinicians should be able to identify whether patients have a false-negative PCR-based test result.
“Can Patients Become Reinfected?”
Reports from China and Japanthat suggest this could be the case, but without further information on whether these were true infections or false-negative tests, it remains unknown. Other coronaviruses demonstrate the ability to reinfect, but that doesn’t typically happen for “many months or years,” according to the authors. “Therefore, it is unlikely that these were true cases of reinfection.” Rhesus macaques who were infected with COVID-19 and then reintroduced to the virus were not infected, they added.
“How Long Does Immunity Last?”
There is no long-term immune response data, but a study from China suggested the median duration of IgM detection was 5 days, while IgG was detected at a median of 14 days after symptom onset. SARS-CoV-1 data, related to this novel coronavirus, suggests that antibodies peaked at 4 months after infection and declined through at least 3 years post-infection.
“How Does SARS-CoV-2 Spread?”
Person-to-person transmission via droplets in the air that contain virus particles, during coughing, sneezing, or talking, the authors said, adding that this usually happens within a distance of 6 feet. While the virus may be able to remain infectious on surfaces for up to 9 days, cleaning and disinfection are effective at decreasing contamination. On a smaller scale, COVID-19 may also be spread through aerosols in circumstances such as intubation, bronchoscopy, suctioning, turning the patient, disconnecting a patient from a ventilator, or performing CPR.
“When Can Social Distancing Measures Be Lifted?”
The authors acknowledged that long-term social distancing can have “detrimental effects on physical and mental health outcomes as well as the economy.” Before a total lift, an ease of restrictions may be more practical, such as identifying asymptomatic and mild cases and isolating those patients to reduce further spread. In Wuhan, most transmissions happened within households, the authors added, so there should be a focus on reducing intra-household spread: the infected person should always wear a mask, they suggested.
“When Will a Vaccine Be Available?”
There were 3 vaccine candidates in phase 1 human trials at the time the authors wrote their paper: 1 mRNA vaccine and 2 adenovirus vector-based vaccines. They estimate a vaccine could be ready by early- to mid-2021.
“Even during a pandemic, obtaining rigorous, reliable data is not a distraction, rather it is essential for accurately measuring the extent and severity of COVID-19 and assessing the effectiveness of the response,” the authors concluded.
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