Latest COVID-19 research focuses on test accuracy, experimental therapies

Recent articles offered differing estimates of the risk of false negatives in testing for SARS-CoV-2, and studies reported the effectiveness of shared ventilators and a cancer drug for patients with severe COVID-19. The FDA revoked its authorization for hydroxychloroquine.


Multiple recent articles looked at testing for SARS-CoV-2. One, published by Clinical Infectious Diseases on June 7, offered some information about the frequency of false negatives from reverse transcription polymerase chain reaction (RT-PCR) tests. The analysis was based on more than 23,000 tests processed by two academic health systems in California and Washington. More than 90% of the initial nasopharyngeal (NP) swab tests were negative, and most patients were not retested. However, 626 of the initially negative patients were retested within a week, and 3.5% had newly positive results. The authors noted that although the study was not designed to determine the true false-negative rate, the results “suggest that false negative NP SARS-CoV-2 RT-PCR results do occur, but potentially at a lower frequency than is currently believed.”

A perspective published by the New England Journal of Medicine on June 5 expressed concern about the possibility of false negatives. It cited multiple studies to estimate that the sensitivity of available tests may be around 70%. The authors called for more information to be provided about tests' clinical sensitivity and specificity and warned that in the meantime, “clinicians should not trust unexpected negative results (i.e., assume a negative result is a ‘false negative’ in a person with typical symptoms and known exposure).”

Another study, published by CHEST on June 10, tried to identify factors that would predict a positive test result. It included more than 10,000 patients tested for SARS-CoV-2 by Cleveland Clinic, including 818 positive results in a development cohort and 290 in a validation cohort. The study found that in addition to known exposure to COVID-19, being male, African-American, or older was associated with a positive result. Positive results were less likely in those who had received a pneumococcal polysaccharide or influenza vaccine or who were taking melatonin, paroxetine, or carvedilol. The authors suggested that the results could be used to conserve testing resources when they are limited and also support further investigation of the effects of the identified drugs on COVID-19.

The CDC also updated and consolidated its recommendations on testing, including interim testing guidelines for nursing home residents and health care personnel, according to a June 13 news release.

Other articles provided data on experimental therapies for COVID-19. Promising results from a British randomized trial of dexamethasone, 6 mg/d, for COVID-19 were reported in a press release. According to the findings, which have not been peer-reviewed, 28-day mortality was significantly lower with the drug than with usual care in ventilated patients (rate ratio [RR], 0.65; 95% CI, 0.48 to 0.88; P=0.0003) and in those on oxygen (RR, 0.80; 95% CI, 0.67 to 0.96; P=0.0021). There was no benefit among patients not requiring respiratory support (RR, 1.22; 95% CI, 0.86 to 1.75; P=0.14).

A report published by the American Journal of Respiratory and Critical Care Medicine on June 9 described how a hospital in New York used one ventilator to simultaneously support two patients with COVID-19 and acute respiratory distress syndrome. Three pairs of patients underwent ventilator sharing during one week in March without adverse events. The authors detail their protocol but also offer a warning about following the model. “The greatest danger of ventilator sharing is wrongly equating the simplicity of its plumbing with ease of safe implementation. Patient selection and management require considerable expertise to ensure safety. Therefore, we recommend a regional referral model wherein ventilator sharing is restricted to expert centers, and patients and ventilators move throughout the region accordingly,” they wrote.

A study published by Science Immunology on June 5 found positive effects from acalabrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma. It was given off-label to 19 patients hospitalized with severe COVID-19 and found to improve oxygenation. Eight of 11 patients who had been on supplemental oxygen were discharged on room air, and four of eight on mechanical ventilation were extubated. “These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial,” the authors said.

Finally, on June 15, the FDA revoked the emergency use authorization that allowed for chloroquine phosphate and hydroxychloroquine sulfate to be used to treat hospitalized patients with COVID-19 outside of clinical trials. The decision was based on emerging scientific data showing that the drugs are unlikely to be effective in treating COVID-19, as well as evidence of serious cardiac adverse events and other side effects, a press release said.