Safety and Efficacy of the COVID-19 Vaccine in Kidney Transplant Recipients

Background: Kidney transplant recipients appear to be at high risk for critical coronavirus disease 2019 (COVID-19) illness. They are considered a priority for COVID-19 vaccination. Only a few studies report on the safety and efficacy of the COVID-19 vaccine in these patients. Methods: In this prospective observational study, we measured anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike-specific IgG post first and second COVID-19 mRNA vaccines in 113 kidney transplant recipients and compared them to 62 healthy volunteers. Result: After the first COVID-19 vaccine, SARS-CoV-2-specific antibodies were undetectable in 38.9% of kidney transplant recipients, and after the second, it remained undetectable in 12.4%. SARS-CoV-2-specific antibodies were significantly lower in kidney transplant recipients. The average antibody titer after the first vaccine was 1243.6±4137.5 in kidney transplant recipients compared to 20012.2±44436.4 in the controls after the first dose (P=0.002), and 7965.5±12431.3 versus 82891.3±67418.7, respectively, after the second dose (P <0.001). The immune response to the COVID-19 vaccine seemed to be influenced by mycophenolate dose in kidney transplant recipients and pre-vaccination infection. Conclusion: Kidney transplant recipients are prone to have attenuated antibody responses (anti-spike IgGs) to mRNA COVID-19 vaccines. Patients on mycophenolate mofetil (2 gm daily) had significantly lower SARS-CoV-2 spike-specific IgG levels as compared to patients on no or reduced dose of mycophenolate. Hence, kidney transplant recipients need to continue all infection control precautionary measures against COVID-19 infection and should be considered a priority for a third COVID-19 vaccine.

COVID-19 vaccines: Global challenges and prospects forum recommendations.

The 11th KAIMRC Annual Research Forum Themed "COVID-19 Vaccine: Global Challenges and Prospects Forum" discussed COVID19 Vaccines. The Forum was a vital event as it provided a hub for leading COVID-19 vaccine scientists, regulators, developers, and distributors to learn about COVID-19 vaccines in development, make decisions about the best vaccines to use, and develop appropriate plans for global distribution and pricing. The COVID-19: Global Efforts for Development, Clinical Trials and Distribution Symposium brought together leading scientists, clinicians, pharma, decision makers, academic institutions and businesses to present and discuss the vaccines that are being currently developed for the COVID19. This event was held to shed light on these vaccines as many are at the late stage of Phase III clinical trials and ready to be marketed. This follows the confusion that few vaccines were produced and pushed into phase III without sharing all the necessary data preventing the scientific and clinical community to judge its efficacy and safety. This event allowed a discussion into the challenges in the distribution, pricing and accessibility of the vaccines. Moreover, the symposium discussed the importance to invest in Biotech-Pharma to combat and overcome any future health crisis. The discussion focused on Saudi Arabia leading initiatives as front runner in the field among G20 members.

Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients.

The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).