A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome. OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS. DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19. METHODS: Data on trial characteristics and intervention characteristics were collected and summarized. RESULTS: After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed. CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.