Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. METHODS: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. RESULTS: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. CONCLUSIONS: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

Computed tomography scan abnormalities in patients with post-acute COVID syndrome

Rationale: Patients recovering from COVID-19 infection can have persistent respiratory symptoms. These symptoms are part of a syndrome of prolonged recovery from of COVID-19 which has been termed 'Post-Acute Covid Syndrome (PACS).' Many patients with PACS have been found to have persistent radiographic changes. It is not known whether these radiographic changes represent developing fibrosis, a developing inflammatory process such as organizing pneumonia, or both. In this study we sought to characterize the radiographic changes seen in patients with persistent pulmonary symptoms. Methods: The medical records of patients who presented to the pulmonary clinic at the Comprehensive COVID Center were reviewed. Computed tomography (CT) scans were reviewed if obtained greater than 4 weeks after COVID diagnosis. If multiple CT scans were performed, the most recent scan was included. Radiographic abnormalities were categorized as inflammatory (ground-glass opacities or consolidation), fibrotic (traction bronchiectasis, reticulation, or honeycombing), both, or neither. Results: 33 patients were evaluated. During the acute phase of COVID infection 8 (24%) were admitted to the intensive care unit, 7 (21%) required mechanical ventilation, and 12 (36%) were admitted to the floor. 20 (61%) patients had CT that fit inclusion criteria. Of the 20 CT scans reviewed, 13 (65%) were abnormal. 10 (50%) scans demonstrated evidence of fibrosis, 11 (55%) scans demonstrated inflammatory changes, and 8 (40%) scans demonstrated both fibrosis and inflammatory changes. The average time from COVID diagnosis to recovery CT was 131 days. The average time from COVID diagnosis to scans with signs of fibrosis was 151 days, whereas the average time from COVID diagnosis to scans with inflammatory changes was 127 days. Conclusion: The etiology of persistent dyspnea in PACS is an area of active investigation, and radiographic patterns of injury may suggest underlying pathologic processes. Our study demonstrates abnormal radiographic findings, including evidence of both fibrotic and inflammatory parenchymal changes, in the majority of patients seen with PACS followed greater than 4 months after initial diagnosis. It is unknown if the ground glass opacities or consolidative changes are representative of post infectious organizing injury or fibrosis that is below the level of detection of CT resolution. Further prospective observational studies are warranted to determine if these changes are progressive, or if interventions such as steroids can expedite respiratory symptom recovery in the setting of a post-acute COVID clinic.

The use of transthoracic echocardiography in patients with persistent respiratory symptoms post COVID-19 illness

Rationale: Acute Coronavirus-19 infection has implications beyond that of primary alveolar injury. Many case reports and autopsy series highlight pulmonary endothelial microvascular dysfunction, thrombosis, and venous thromboembolism as outcomes of acute coronavirus-19 illness. It is uncertain whether persistent symptoms of dyspnea after COVID-19 infection may signal an increased likelihood of fibrotic lung disease, pulmonary vascular dysfunction, or both. Here, we describe the incidence of post COVID-19 surveillance for right ventricular (RV) dysfunction in a cohort enriched for persistent symptoms after infection. Methods: We reviewed the records of patients referred to a Comprehensive COVID Center at a large urban academic medical center. Manual chart abstraction was used to collect demographic and clinical data during both acute and recovery phases of illness. Computed tomography scans (CT), transthoracic echocardiography, and laboratory data were obtained as part of clinical care. Strain images were captured as part of clinical practice, utilizing TomTec software. Patient were enrolled in a registry approved by the institutional review board. Results: Over the course of six weeks, 33 patients were referred to the pulmonary COVID recovery clinic for persistent shortness of breath or cough. Of the 33 patients evaluated, 20 (61%) were evaluated with diagnostic computed tomography scans and 13 (39%) with transthoracic echo imaging during their recovery phase marked by persistent symptoms. 3 of the 13 (23%) patients with transthoracic echos had evidence of RV dysfunction as determined by right ventricular free wall strain (> -20%) or tricuspid annular plane systolic excursion (<16mm). These three patients did not have concomitant echocardiographic evidence of LV dysfunction (depressed left ventricular ejection fraction or increased left ventricular global longitudinal strain). None of the patients with RV dysfunction had venous thromboembolic events during acute illness, and 2 of the 3 were managed in the intensive care unit (ICU) both of which have evidence of fibrosis on recovery CT scans. Conclusion Transthoracic echocardiography should be considered in post COVID recovery patients with persistent limitations of dyspnea. The noticeable frequency of abnormal right ventricular function, in the presence of normal left ventricular function, may suggest an increased signal of right ventricular dysfunction secondary to chronic pulmonary microvascular disease or complications of restrictive lung physiology after COVID viral pneumonia. These findings warrant further review in larger cohorts with particular attention to the post ICU population.