IDSA offers criteria on testing for COVID-19; new research looks at clots, treatments

Last week, the Infectious Diseases Society of America (IDSA) released the third section of its three-part guideline addressing COVID-19, focusing on testing. The guideline which was developed by an expert panel and released on May 6, includes 15 recommendations for SARS-CoV-2 testing and an algorithm to further aid decision making.

Among other advice, the guideline recommends SARS-CoV-2 nucleic acid amplification testing in symptomatic patients, even when the clinical suspicion for COVID-19 is low. It suggests using nasopharyngeal, mid-turbinate, or nasal swabs rather than oropharyngeal swabs or saliva alone. For hospitalized patients, the guideline suggests initially obtaining an upper respiratory tract sample rather than a lower respiratory sample. If that is negative, and the suspicion for disease remains high, collecting a lower respiratory tract sample is suggested. Repeating viral RNA testing after an initial negative test result is suggested in symptomatic patients with an intermediate or high clinical suspicion of COVID-19, but not in patients with low clinical suspicion.

Regarding asymptomatic patients, the panel suggests testing those known or suspected to have been exposed to the virus. Testing in those being hospitalized for other reasons depends on community prevalence of COVID-19: The recommendations suggest against it when prevalence is low and recommend it when it is high. However, testing is recommended in such patients if they are immunocompromised or about to undergo an immunosuppressive procedure. Testing is suggested before major surgery but is only recommended before an aerosol-generating procedure if personal protective equipment (PPE) is limited.

In research news, the effects of anticoagulation were analyzed by a retrospective study of 2,773 hospitalized COVID-19 patients in New York, 28% of whom received systemic anticoagulation, published as a research letter in the Journal of the American College of Cardiology on May 6. In-hospital mortality was 22.5% in patients who received anticoagulation and 22.8% in patients who did not. In the 395 patients who required mechanical ventilation, mortality rates were 29.1% and 62.7%, respectively. A multivariate proportional hazards model showed that longer duration of anticoagulation was associated with reduced risk of mortality (adjusted hazard ratio, 0.86 per day; 95% CI, 0.82 to 0.89; P<0.001). Bleeding event rates were 1.9% without anticoagulation versus 3% with it (P=0.2). “Although limited by its observational nature, unobserved confounding, unknown indication for AC [anticoagulation], lack of metrics to further classify illness severity in the mechanically ventilated subgroup, and indication bias, our findings suggest that systemic AC may be associated with improved outcomes among patients hospitalized with COVID-19,” the authors said. They cautioned that anticoagulant therapy should be individualized and that the risk of bleeding should be considered.

A small autopsy study, published by Annals of Internal Medicine on May 6, highlighted the potential role of venous thromboembolism in mortality from COVID-19. It included the first 12 consecutive COVID-19-positive deaths at one German medical center. Autopsies revealed deep venous thrombosis in seven patients (58%) and pulmonary embolism as the direct cause of death in four patients. Additionally, postmortem CT revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, while histomorphologically diffuse alveolar damage was seen in eight patients. “When hemodynamic deterioration occurs in a patient with COVID-19, pulmonary embolism should always be suspected. That patients with COVID-19 who have increased D-dimer levels, a sign of coagulopathy, may benefit from anticoagulant treatment seems plausible,” said the study authors.

A letter to the New England Journal of Medicine (NEJM) addressed prolonged activated partial-thromboplastin time (aPTT) among hospitalized patients with COVID-19. The authors found prolonged aPTT in 20% of 216 studied patients, as well as higher than normal prevalence of lupus anticoagulant and associated factor XII deficiency, neither of which is associated with increased risk of bleeding, they noted. “In our opinion, clinicians should not withhold use of anticoagulants for thrombosis while awaiting further investigation of a prolonged aPTT, nor should they withhold thrombolytic therapy in the face of a high-risk pulmonary embolism on the basis of a prolonged aPTT alone,” the authors said.

Studies of drugs for COVID-19 offered mixed results this week. Potentially positive data were reported by a retrospective study of non-ventilated Italian patients with COVID-19 and acute respiratory distress syndrome. Twenty-nine patients who received high doses of anakinra (a recombinant interleukin-1 receptor antagonist) were compared to 16 receiving standard treatment. At 21 days, survival was significantly higher in the anakinra group (90% vs. 56%; P=0.009), but mechanical ventilation-free survival did not differ significantly (72% vs. 50%; P=0.15), according to results published by The Lancet Rheumatology on May 7. “The uncontrolled nature of our study mandates caution in interpretation of findings, and validation is absolutely required in a controlled setting,” the authors said. “Controlled evidence is awaited, as IL-1 blockade with high-dose intravenous anakinra deserves consideration among anti-inflammatory treatments for COVID-19.”

An observational study, published by NEJM on May 7, looked at 811 New York patients given hydroxychloroquine and found that the drug wasn't associated with any significant change in a composite end point of intubation or death. The authors said their results do not rule out either benefit or harm of the drug but do not support its use outside randomized clinical trials. A randomized trial published by NEJM the same day found no significant benefit from lopinavir-ritonavir in 99 Chinese patients treated with the drug versus 100 receiving standard care. Whether combining the drug with other antiviral agents “might enhance antiviral effects and improve clinical outcomes remains to be determined,” the authors said.