COVID-19 in the Literature
A digest of published pieces on novel coronavirus.
In December 2019, Wuhan, China, experienced the beginning of an outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). That outbreak grew to an epidemic, and the epidemic then grew to a pandemic. The literature on the COVID-19 pandemic and the virus that causes it is swiftly growing as the world confronts this novel disease. Here, we present summaries of a sampling of recent publications.
Clinical Course and Risk Factors for Mortality of Adult Inpatients With COVID-19 in Wuhan, China: A Retrospective Cohort Study
Zhou F, Yu T, Du R, et al.1
In this retrospective, multicenter cohort study, the authors examined risk factors for mortality in all adult inpatients with laboratory-confirmed COVID-19 at two hospitals in China who had been discharged (n = 137) or had died (n = 54) by January 31, 2020.
Older age, higher sequential organ failure assessment score, and d-dimer greater than 1 μg/L on admission to hospital were associated with higher rates of death due to COVID-19, the authors found.1
Nearly half of the patients in the study presented with comorbidities, led by hypertension (30% of patients), diabetes (19%), and coronary heart disease (8%). Viral shedding persisted for a median of 20 days in survivors, and SARS-CoV-2 RNA was detectable until death in nonsurvivors.
These data “could help clinicians to identify patients with poor prognosis at an early stage,” the study authors wrote. The prolonged viral shedding observed in the study “provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” they concluded.
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe COVID-19
Cao B, Wang Y, Wen D, et al.2
To date, no drug has been proven to be effective for the treatment of COVID-19. Cao et al conducted a randomized, controlled, open-label trial of treatment with the combination of lopinavir and ritonavir in hospitalized adult patients with confirmed SARS-CoV-2 infection. They found that the treatment provided no benefit compared with standard of care in hospitalized adult patients with COVID-19.
Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement, mortality at 28 days, or percentages of patients with detectable viral RNA at multiple time points. A modified intention-to-treat analysis showed that lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that with standard of care.
Interventions to Mitigate Early Spread of SARS-CoV-2 in Singapore: A Modeling Study
Koo JR, Cook AR, Park M, et al.3
Since the beginning of the SARS-CoV-2 outbreak, the virus has been imported to more than 170 countries on six continents.4 Researchers in Singapore investigated options for early intervention to prevent disease spread once community transmission of the virus has been detected. They determined that a combination of strategies—including isolation of infected individuals and quarantining of family members, school closure, and workplace distancing—was the most effective method and could substantially reduce the number of infections. The model made assumptions about the reproduction number (the expected number of cases directly generated by one case) and the percentage of infections that are symptomatic. “When these variables are increased, the authors said, “the effectiveness of the intervention could be substantially reduced.”
Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients
Yu Jun IS, Anderson DE, Zheng Kang AE, et al.5
SARS-CoV-2 is known to be transmitted via droplets, but other routes of transmission—such as through infected ocular tissues or fluids—are unknown. It has been hypothesized that the nasolacrimal system might act as a conduit for viruses to travel from the upper respiratory tract to the eye, and, therefore, ocular tissues and fluids might be a potential source of transmission.
This study by Yu et al suggests that the risk of transmission through tears, regardless of the phase of infection, is likely to be low. These authors attempted to determine the possibility of transmission through tears by comparing viral shedding in tears with nasopharyngeal swabs (NP) throughout the course of infection in 17 patients with COVID-19. Tears were collected with Schirmer test strips at various time points from day 3 to day 20 after onset of symptoms and sent to a research laboratory for processing. NPs were assessed at a diagnostic laboratory. No patients presented with ocular symptoms, but one patient developed conjunctival injection and chemosis during the study. Of the 64 tear samples taken during the study period, all tested negative for SARS-CoV-2, including the patient who developed ocular symptoms.
“All tear samples tested negative even when NPs continued to test positive,” the authors concluded. “Furthermore, patients with symptoms of upper respiratory tract infections did not demonstrate any viral shedding in tears, suggesting the hypothesis of the lacrimal duct as a viral conduit may not be true.”
Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients With Coronavirus Disease 2019 — United States, February 12–March 28, 2020
CDC COVID-19 Response Team.6
People in the United States with underlying health conditions appear to be at higher risk for more severe COVID-19, consistent with findings from other countries, according to the Centers for Disease Control and Prevention (CDC) COVID-19 Response Team. The team reached this conclusion after analyzing data from laboratory-confirmed COVID-19 cases reported to the CDC with dates of onset from February 12 through March 28.
Among the 122,653 US COVID-19 cases reported to the CDC as of March 28, 7,162 (5.8%) patients had data available pertaining to underlying health conditions or risk factors. Among these patients, these authors found, higher percentages of patients with underlying conditions were admitted to the hospital and to an intensive care unit (ICU) than were patients without reported underlying conditions. Specifically, out of 457 ICU admissions, 358 (78%) were for patients with one or more reported underlying health condition. Similarly, among 1,037 non-ICU hospitalizations, 732 (71%) were for people with such conditions. By contrast, of 5,143 COVID-19 patients who were not hospitalized, 1,388 (27%) were reported to have at least one underlying health condition.
“These results are consistent with findings from China and Italy, which suggest that patients with underlying health conditions and risk factors, including, but not limited to, diabetes mellitus, hypertension, [chronic obstructive pulmonary disease], coronary artery disease, cerebrovascular disease, chronic renal disease, and smoking, might be at higher risk for severe disease or death from COVID-19,” the study authors said. They noted that their analysis was limited by small numbers and missing data, and the findings might change as additional data become available.
1. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.
2. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe covid-19 [published online ahead of print March 18, 2020]. N Engl J Med.
3. Koo JR, Cook AR, Park M, et al. Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study [published online ahead of print March 23, 2020]. Lancet Infect Dis.
4. Mapping the worldwide spread of the coronavirus. Washington Post. https://www.washingtonpost.com/graphics/2020/world/mapping-spread-new-coronavirus/. Accessed March 31, 2020.
5. Yu Jun IS, Anderson DE, Zheng Kang AE, et al. Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-19) patients. Ophthalmology. 2020 [journal pre-proof].
6. CDC COVID-19 Response Team. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019. United States, February 12-March 28, 2020 [published online ahead of print March 31, 2020]. MMWR Morb Mortal Wkly Rep.