Data regarding COVID-19 outcomes in solid organ transplant recipients(SOTr) across SARS-CoV-2 waves, including the impact of different measures, is lacking. This cohort study, conducted from March 2020-May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1,975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, ICU admission, and 30-day and 1-year all-cause mortality. SARS-CoV-2 waves were categorized as Wildtype/Alpha/Delta(318 cases, 16.1%), Omicron-BA.1(268, 26.2%), Omicron-BA.2(268, 13.6%), Omicron-BA.5(561, 28.4%), Omicron-BQ.1.1(188, 9.5%), and Omicron-XBB.1.5(123, 6.2%). Severe COVID-19 rate was highest during the Wildtype/Alpha/Delta wave(44.6%), and lower in Omicron waves(5.7-16.1%). Lung transplantation was associated with severe COVID-19(OR:4.62, 95%CI:2.71-7.89), along with rituximab treatment(OR:4.24, 95%CI:1.04-17.3), long-term corticosteroid use(OR:3.11, 95%CI:1.46-6.62), older age(OR: 1.51, 95%CI:1.30-1.76), chronic lung disease(OR:2.11, 95%CI:1.36-3.30), chronic kidney disease(OR:2.18, 95%CI:1.17-4.07), and diabetes(OR:1.97, 95%CI:1.37-2.83). Early treatment and ≥3 vaccine doses were associated with reduced severity(OR: 0.29, 95%CI:0.19-0.46, and 0.35, 95%CI:0.21-0.60, respectively). Tixagevimab/cilgavimab and bivalent boosters did not show a significant impact. The study concludes that COVID-19 severity decreased across different variants in SOTr. Lung transplantation was associated with worse outcomes and may benefit more from preventive and early therapeutic interventions.

Preventive strategies in the form of early identification and isolation of patients are the cornerstones in the control of COVID-19 pandemic. We have conducted this study to develop a clinical symptom-based scoring system (CSBSS) for the diagnostic evaluation of COVID-19. In this study, 378 patients presenting to screening outpatient clinic with clinical suspicion of COVID-19 were evaluated for various clinical symptoms. Statistical associations between presenting symptoms and reverse transcription-polymerase chain reaction (RT-PCR) results were analysed to select statistically significant clinical symptoms to design a scoring formula. CSBSS was developed by evaluating clinical symptoms in 70% of the total patients. The cut-off score of the CSBSS was determined from ROC (receiver operating characteristics) curve analysis to obtain a cut-off for optimum sensitivity and specificity. Subsequently, developed CSBSS was validated in the external validation dataset comprising 30% of patients. Clinical symptoms like fever >100⁰F, myalgia, headache, cough and loss of smell had significant association with RT-PCR result. The adjusted odds ratios (95% confidence interval [CI]) for loss of smell, fever >100°F, headache, cough and myalgia were 5.00 (1.78-13.99), 2.05 (1.36-3.07), 1.31 (0.67-2.59), 1.26 (0.70-2.26) and 1.18 (0.50-2.78), respectively. The ROC curve and area under the curve of development and validation datasets were similar. The presence of fever >100°F and loss of smell among suspected patients are important clinical predictors for the diagnosis of COVID-19. This newly developed CSBSS is a valid screening tool that can be useful in the diagnostic evaluation of patients with suspected COVID-19. This can be used for the risk stratification of the suspected patients before their RT-PCR results are generated.

Preventive practices are the mainstay to mitigate the spread of the COVID-19 pandemic. We tried to assess the self-reported adherence of our participants to the already known preventive practices. Furthermore, we tried to determine whether the non-compliance to specific preventive practices was associated with the acquisition of the infection or not. We enrolled 379 healthcare workers, hospital staff, and their family members who were tested for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) in an outpatient clinic. Socio-demography and the infection prevention practices of the individuals were recorded in a preformed questionnaire. Statistical analysis was performed to find out the statistical association between these factors and the RT-PCR results. Adjusted and unadjusted odds ratios were determined to find out the degree of protection provided by each of the preventive practices concerning the development of the disease. Social distancing (p<0.001), hand hygiene (p<0.001), ensuring N-95 mask fit check (p<0.001), and the use of alternative medications (p=0.002) were found to be protective. Resident doctors were at a lower risk of developing the disease as compared to the other healthcare workers (odds ratio: 0.39). The failure to practice the already known preventive practices is probably one of the most important factors in the progression of the COVID-19 pandemic. Adherence to these practices is the intervention of choice to reduce disease transmission in the current scenario.

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are susceptible to severe COVID-19 outcomes. Most guidelines recommend a fourth dose (i.e., booster) COVID-19 vaccine to reduce the infection risk, and observational studies are required to determine the immunogenicity and safety of the booster dose in this population. The primary outcome was to determine the quantitative anti-receptor binding domain (RBD) antibody titers after the fourth dose of the COVID-19 vaccine. The secondary outcomes included adverse effects and all-cause mortality. In this single-group prospective cohort, we included allogeneic HSCT patients aged ≥18 who received the fourth dose of COVID-19 mRNA vaccine between December 15, 2021, and August 2, 2022. We excluded patients with a history of COVID-19 diagnosis and those who received IVIG within 21 days of antibody testing or rituximab within six months before cohort entry. We used regression models to determine the contributing factors significantly associated with post-4^th-dose anti-RBD titer. Sixty-seven patients [median (IQR) age: 59.5 (53.5-65.5) years, 33 male (61%)] received the fourth dose of vaccine, and 54 were included in the anti-RBD titer analysis. The median anti-RBD titer, 4-6 weeks after the third and fourth doses, were significantly different [13,350 (2,618 - 34,740) U/ml and 44,500 (11,163 - 84,330) U/ml, respectively, p < 0.0001]. In univariate analysis, the post-third-dose anti-RBD titer (β: 0.70; CI95%: 0.54 to 0.87, p<0.001), and treatment with mycophenolate compounds (β: -1.05; CI95%: -1.97 to -1.12, p=0.03) significantly predicted the antibody response to the 4^th dose. In multivariate analysis, the inverse association between treatment with mycophenolate compounds and the post-fourth-dose anti-RBD antibody titer was not significant (β: -0.57; CI95%: -1.32 to 0.19, p=0.14), while the significant association between the anti-RBD titres following the third and fourth doses did not considerably change (β: 0.66; CI95%: 0.47 to 0.86, p<0.001). The most frequent adverse event was vaccination site soreness (44%), followed by fatigue (16%), myalgia (4%) and headache (2%). No recipient experienced new or worsening pre-existing graft-versus-host disease (GvHD) within 40 days of vaccination, and no patient died. Six patients (11%) developed breakthrough SARS-CoV-2 infections not associated with hospitalization or severe outcomes. The fourth dose of the COVID-19 vaccine appears to be highly immunogenic and safe in allogeneic HSCT patients. Further studies are needed to determine the neutralizing antibody titers against SARS-CoV-2 subvariants and the effectiveness and immunogenicity of bivalent vaccines in allogeneic stem cell transplant recipients.

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.