A narrative review of COVID-19-related acute respiratory distress syndrome (CARDS): "typical" or "atypical" ARDS?

Background and Objective: The coronavirus disease of 2019 (COVID-19) is highly infectious and mainly involves the respiratory system, with some patients rapidly progress to acute respiratory distress syndrome (ARDS), which is the leading cause of death in COVID-19 patients. Hence, fully understanding the features of COVID-19-related ARDS (CARDS) and early management of this disease would improve the prognosis and reduce the mortality of severe COVID-19. With the development of recent studies which have focused on CARDS, whether CARDS is "typical" or "atypical" ARDS has become a hotly debated topic. Methods: We searched for relevant literature from 1999 to 2021 published in PubMed by using the following keywords and their combinations: "COVID-19", "CARDS", "ARDS", "pathophysiological mechanism", "clinical manifestations", "prognosis", and "clinical trials". Then, we analyzed, compared and highlighted the differences between classic ARDS and CARDS from all of the aspects above. Key Content and Findings: Classical ARDS commonly occurs within 1 week after a predisposing cause, yet the median time from symptoms onset to CARDS is longer than that of classical ARDS, manifesting within a period of 9.0-12.0 days. Although the lung mechanics exhibited in CARDS grossly match those of classical ARDS, there are some atypical manifestations of CARDS: the severity of hypoxemia seemed not to be proportional to injury of lung mechanics and an increase of thrombogenic processes. Meanwhile, some patients' symptoms do not correspond with the extent of the organic injury: a chest computed tomography (CT) will reveal the severe and diffuse lung injuries, yet the clinical presentations of patients can be mild. Conclusions: Despite the differences between the CARDS and ARDS, in addition to the treatment of antivirals, clinicians should continue to follow the accepted evidence-based framework for managing all ARDS cases, including CARDS.

Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies.

Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of the understanding of the biological regulation mechanisms underlying COVID-19, alternative or novel therapeutic targets for COVID-19 treatment are still urgently required. SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19. Both the virus and host factors are potential targets for antiviral therapy. Hence, in this study, the current therapeutic strategies of COVID-19 have been classified into "target virus" and "target host" categories. Repurposing drugs, emerging approaches, and promising potential targets are the implementations of the above two strategies. First, a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians. Additionally, their unavailability in the fight against COVID-19 was analyzed. Next, a profound analysis of the emerging approaches was conducted, particularly all licensed vaccines and monoclonal antibodies (mAbs) enrolled in clinical trials against primary SARS-CoV-2 and mutant strains. Furthermore, the pros and cons of the present licensed vaccines were compared from different perspectives. Finally, the most promising potential targets were reviewed, and the update of the progress of treatments has been summarized based on these reviews.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility.

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.