Inhaled Nitric Oxide for Clinical Management of COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Severe COVID-19 is associated with hypoxemia and acute respiratory distress syndrome (ARDS), which may predispose multiorgan failure and death. Inhaled nitric oxide (iNO) is a clinical vasodilator used in the management of acute respiratory distress syndrome (ARDS). This study evaluated the response rate to iNO in patients with COVID-19-ARDS. METHOD: We searched Medline and Embase databases in May 2022, and data on the use of iNO in the treatment of ARDS in COVID-19 patients were synthesized from studies that satisfied predefined inclusion criteria. A systematic synthesis of data was performed followed by meta-analysis. We performed the funnel plot and leave-one-out sensitivity test on the included studies to assess publication bias and possible exaggerated effect size. We compared the effect size of the studies from the Unites States with those from other countries and performed meta-regression to assess the effect of age, year of publication, and concomitant vasodilator use on the effect size. RESULTS: A total of 17 studies (including 712 COVID-19 patients) were included in this systematic review of which 8 studies (involving 265 COVID-19 patients) were subjected to meta-analysis. The overall response rate was 66% (95% CI, 47-84%) with significantly high between-studies heterogeneity (I2 = 94%, p < 0.001). The funnel plot showed publication bias, although the sensitivity test using leave-one-out analysis showed that removing any of the study does not remove the significance of the result. The response rate was higher in the Unites States, and meta-regression showed that age, year of publication, and use of concomitant vasodilators did not influence the response rate to iNO. CONCLUSION: iNO therapy is valuable in the treatment of hypoxemia in COVID-19 patients and may improve systemic oxygenation in patients with COVID-19-ARDS. Future studies should investigate the mechanism of the activity of iNO in COVID-19 patients to provide insight into the unexplored potential of iNO in general ARDS.

HIV infection and the implication for COVID‐19 vaccination

Human immunodeficiency virus (HIV) is associated with altered cellular and humoral immune response, especially in patients with an untreated or chronic infection. This may be due to direct and/or indirect HIV viral activities resulting in T‐ and B‐cells dysfunctions. Although still unclear, various studies have proposed that HIV infection may exacerbate the clinical outcomes of COVID‐19. Indeed, COVID‐19 vaccines were developed in record time and have been shown to reduce the severity of COVID‐19 in the general population. These vaccines were also earmarked as a solution to global disruptions caused by the COVID‐19 pandemic. HIV infection has been reported to reduce the efficacy of various other vaccines including those used against Streptococcus pneumoniae, Clostridium tetani, and influenza viruses. However, current guidelines for the administration of available COVID‐19 vaccines do not account for the immune‐compromised state of people living with HIV (PLWH). We discuss here the potentials, nature, and implications of this HIV‐induced dampening of the humoral immune response on COVID‐19 vaccines by first reviewing the literature about efficacy of previous vaccines in PLWH, and then assessing the proportion of PLWH included in phase III clinical trials of the COVID‐19 vaccines currently available. The clinical and public health implications as well as suggestions for governments and non‐governmental organizations are also proposed in the context of whether findings on the safety and efficacy of the vaccines could be extended to PLWH. Impacts The human immunodeficiency virus (HIV) is characterized by attenuated humoral immunity that may reduce the efficacy of vaccines in people living with HIV (PLWH). Vaccination against the SARS‐CoV‐2 infection remains the main public health answer to the COVID‐19 pandemic. Although no significant safety concerns have been raised regarding the COVID‐19 vaccines in PLWH, the efficacy of these vaccines in PLWH has not received due attention. Indeed, phase III clinical trials for the safety and efficacy of COVID‐19 vaccines involved a significantly low number of PLWH. There are major gaps in knowledge on the efficacy of COVID‐19 vaccines in PLWH and until further research is carried out, PLWH should be prioritized along with other at‐risk groups for repeated vaccination and safeguard. Direct and indirect effect of HIV viraemia on B‐cell population and activity is linked with sub‐optimal efficacy of vaccines in people living with HIV (PLWH) through quantitative or qualitative reduction in elicited immune response (neutralizing antibodies). The proportion of PLWH included in phase III clinical trials of COVID‐19 vaccines is significantly low and extension of findings to this population may be misleading. We discuss here the implication of these factors on COVID‐19 vaccines efficacy in PLWH.