Risk of re-infection, benefits of anticoagulation, cause of sex differences among COVID-19 research

On Aug. 28, the FDA broadened its emergency use authorization (EUA) for remdesivir to cover all patients hospitalized with suspected or confirmed COVID-19. The previous EUA, issued in May, applied only to patients with severe disease.

The first peer-reviewed data indicating a patient was re-infected with SARS-CoV-2 were published by Clinical Infectious Diseases on Aug. 25. The 33-year-old man living in Hong Kong had an initial symptomatic COVID-19 infection, tested negative after recovery, and then tested positive on airport screening 142 days later. During the second, asymptomatic infection, there was serological evidence of elevated C-reactive protein level and SARS-CoV-2 IgG seroconversion, and genetic analysis showed that viral genomes from the first and second episodes belonged to different clades/lineages. “Our findings suggest that SARS-CoV-2 may persist in humans as is the case for other common-cold associated human coronaviruses, even if patients have acquired immunity via natural infection or via vaccination,” the authors said. This suggests that previously infected people should maintain social distancing and hygiene measures and be vaccinated, they added.

Patients who received anticoagulation during their hospitalization for COVID-19 had significantly lower risk of mortality and intubation, according to a study published by the Journal of the American College of Cardiology on Aug. 26. It included 4,389 patients from one New York health system: 34.9% on no anticoagulation, 20.5% on a therapeutic dose, and 44.6% on a prophylactic dose. Both therapeutic and prophylactic anticoagulation were associated with significantly reduced rates of in-hospital mortality (adjusted hazard ratios [aHRs], 0.53 [95% CI, 0.45 to 0.62] and 0.50 [95% CI, 0.45 to 0.57], respectively) and intubation (aHRs, 0.69 [95% CI, 0.51 to 0.94] and 0.72 [95% CI, 0.58 to 0.89], respectively). When anticoagulation was initiated within 48 hours of admission, there was no statistically significant difference between therapeutic and prophylactic doses for either of these outcomes. Bleeding rates were low in all groups but highest with therapeutic anticoagulation. The findings were corroborated by autopsies of 26 patients, 11 of whom had previously unsuspected thromboembolic disease; of these, only three were on therapeutic anticoagulation. The study authors suggested that the observational data be used to inform trials to determine optimal anticoagulant regimens in COVID-19 patients.

Advice on diagnosing and managing pulmonary embolism (PE) in patients with COVID-19 was offered by a new position paper from The National Pulmonary Embolism Response Team (PERT) Consortium, published by CHEST on Aug. 26. Among other guidance, it recommends a high index of suspicion for concurrent PE in patients with COVID-19. Elevated D-dimer alone should not be used for diagnosis. For patients with mild COVID-19 symptoms and low-risk PE, outpatient treatment or early discharge may be considered. The indications and contraindications for thrombolysis remain unchanged, and systemic thrombolysis should be considered in patients for whom an invasive approach would be appropriate but is not available due to limited resources or concerns about viral transmission. The consortium recommended a multidisciplinary approach and noted that PERT consultation provides a mechanism for evaluation of complex interventional options. The position paper also addresses protection of clinicians, transfers, and follow-up care.

Living systematic reviews from Annals of Internal Medicine on hydroxychloroquine and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) were updated last week. The update on hydroxychloroquine found several new studies and concluded that “there is now low strength of evidence from trials and cohort studies that hydroxychloroquine has no positive effect on all-cause mortality and need for mechanical ventilation.” Previously the evidence had been determined insufficient. The other update found 17 new studies, but nothing that changed the level of certainty that ACEIs and ARBs are not associated with severe illness or infection risk. “Although there is a signal toward improved outcomes among patients with COVID-19 who continue use of ACEIs or ARBs, the benefits and harms of initiating ACEIs or ARBs (that is, new users) in COVID-19 treatment remains unclear,” the update said.

Finally, a potential explanation for differences in COVID-19 outcomes between men and women was offered by a study published by Nature on Aug. 26. It compared plasma from 98 patients treated for COVID-19 at one hospital to uninfected health care workers and found that infected men had higher plasma levels of innate immune cytokines and more robust induction of nonclassical monocytes, while infected women mounted a significantly more robust T-cell response. Poor T-cell response was negatively correlated with age and was associated with worse disease outcome in men but not women. The reverse was true of higher innate immune cytokines. “Collectively, these data suggest that vaccines and therapies to elevate T cell immune response to SARS-CoV-2 might be warranted for male patients, while female patients might benefit from therapies that dampen innate immune activation early during disease. Immune landscape in COVID-19 patients is considerably different between the sexes, and these differences may underlie heightened disease susceptibility in men,” the authors wrote.