Immunogenicity, clinical efficacy and safety of additional second COVID-19 booster vaccines against Omicron and its subvariants: A systematic review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

Efficacy of low-dose lung radiotherapy in the management of COVID-19 patients: a randomised, open-label study.

OBJECTIVE: Evaluate role of low-dose radiotherapy (LDRT) in COVID-19 pneumonia. METHODS: Sixty-five patients 40 years or older tested positive for COVID-19 reverse transcriptase-polymerase chain reaction with mild to moderate acute respiratory distress syndrome (ARDS), were randomised 1:1, from 4 June 2021, to either best standard of care (control arm) according to the Indian Council of Medical Research guidelines or a single dose of LDRT (LDRT-0.5Gy) to both lungs along with best standard of care (experimental arm). The primary outcome was either progression to severe disease (PaO2/FiO2 ratio <100 mmHg) within 28 days of randomisation or all-cause mortality at 28 days. If the primary outcome could have been prevented, it was considered "favourable"; if not, it was considered "unfavourable." RESULTS: Thirty-three patients were allocated to experimental arm, 32 to control arm. An intention to treat analysis was performed. Unfavourable outcome was seen in 5 (15.2%) patients in experimental arm, vs , 12 (37.5%) patients in control arm, odds of an unfavourable outcome in experimental arm were 0.3, 95% CI 0.09-0.97; two-sided p = 0.04. Four and five patients died in experimental and control arm, respectively. No radiation-induced toxicity was observed. CONCLUSION: LDRT reduced the number of patients with unfavourable outcome at 28 days. ADVANCES IN KNOWLEDGE: One of the few randomised studies showing reduced unfavourable outcome in mild to moderate ARDS COVID-19 patients receiving LDRT.CTRI/2021/06/034001, Clinical Trials Registry - India (ICMR-NIMS).

Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175.

BACKGROUND: A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-1(19), the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. METHOD: Healthy malaria naïve Indian male subjects aged 18-45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10 µg, 25 µg and 50 µg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. RESULTS: JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-1(19). Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. CONCLUSION: Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-1(19) construct needs to be optimised to improve its immunogenicity. TRIAL REGISTRATION: Clinical Trial Registry, India CTRI/2010/091/000301.

Sphincterotomy in patients with gallstones, elevated LFTs and a normal CBD on ERCP.

BACKGROUND/AIMS: To determine whether an endoscopic sphincterotomy affects outcome in patients with symptomatic gallstones, elevated liver function tests and a normal common bile duct on endoscopic retrograde cholangiopancreatogram. METHODOLOGY: A total of 163 patients with symptomatic gallstones and elevated liver function tests, and found to have a normal common bile duct on endoscopic retrograde cholangiopancreatogram were included in the study. Endoscopic sphincterotomy was performed in 78 (47.8%) patients, while 85 (52.1%) patients did not have an endoscopic sphincterotomy. The two groups were compared for detection of small unseen common bile duct stones/debris, endoscopic retrograde cholangiopancreatogram related complications, and biliary complications after cholecystectomy. RESULTS: Small common bile duct stones/debris were recovered in 11/43 (25.5%) patients who had instrumentation of the common bile duct performed after endoscopic sphincterotomy. Common bile duct instrumentation was not performed in any of the patients without endoscopic sphincterotomy. No patient had any biliary complication after cholecystectomy, both in the immediate postoperative period and on a follow-up of 37.5 +/- 13.6 months (range 17-66). Endoscopic retrograde cholangiopancreatogram related complications occurred in 8 patients who had an endoscopic sphincterotomy and in 2 without endoscopic sphincterotomy (p < 0.05). CONCLUSIONS: Performing an endoscopic sphincterotomy in these patients increases the detection of small unseen common bile duct stones/debris without changing the clinical outcome after cholecystectomy. It also increases the endoscopic retrograde cholangiopancreatogram related complication rate, and therefore may not be necessary.