Dengue versus COVID-19: Comparing the incidence of cardiovascular, neuropsychiatric, and autoimmune complications.

BACKGROUND AND AIMS: While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was contrasted against that following SARS-CoV-2 infection in a multi-ethnic adult Asian population. METHODS: National testing and healthcare claims databases in Singapore were utilised to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 Jul 2021-31 Oct 2022). Risks of new-incident cardiovascular/neuropsychiatric/autoimmune complications 31-300 days post-dengue infection, contrasted with SARS-CoV-2 infection were estimated using Cox regression with overlap weights. Risks were reported in terms of adjusted-hazard-ratio (aHR) and excess-burden (EB) per-1000-persons. RESULTS: 11 707 dengue-infected individuals and 1 248 326 contemporaneous COVID-19 cases were included; the majority had mild initial infection not requiring hospitalisation. Amongst dengue-infected individuals, there was 21% (aHR = 1.21 [1.06-1.38]) increased risk of any sequelae, with 55% (aHR = 1.55 [1.27-1.89]) increased risk of cardiovascular sequelae. Specifically, increased risk of dysrhythmias (aHR = 1.79[1.35-2.37]), ischemic-heart-disease (aHR = 1.45[1.12-1.89]), other cardiac disorders (aHR = 2.21[1.54-3.16]) and thrombotic disorders (aHR = 2.55[1.50-4.35]) was noted. Elevated risk of individual neuropsychiatric sequelae, including cerebrovascular disorders (aHR = 1.49[1.09-2.13]), cognition/memory disorders (aHR = 2.13[1.55-2.93]), extrapyramidal/movement disorders (aHR = 1.98[1.33-2.94]) and anxiety disorders (aHR = 1.61[1.01-2.56]) was observed in dengue-infected individuals compared to COVID-19 cases. Elevated risks of post-acute sequelae in dengue survivors were observed when contrasted against COVID-19 survivors infected during Delta/Omicron predominance, as well as across vaccination strata. CONCLUSIONS: Increased risk of post-acute cardiovascular/neuropsychiatric complications was observed in dengue survivors, when contrasted against COVID-19 survivors infected during Delta/Omicron predominance.

Intravenous fluid therapy in hospitalized adult dengue patients without shock: Impact on subsequent severe dengue and potential adverse effects.

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazard ratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.

Neutrophils - an understudied bystander in dengue?

Dengue is a mosquito-borne viral disease which causes significant morbidity and mortality each year. Previous research has proposed several mechanisms of pathogenicity that mainly involve the dengue virus and host humoral immunity. However, innate immune cells, such as neutrophils, may also play an important role in dengue, albeit a much less defined role. In this review, we discuss the emerging roles of neutrophils in dengue and their involvement in pathologies associated with severe dengue. We also describe the potential use of several neutrophil proteins as biomarkers for severe dengue. These studies suggest that neutrophils are important players in dengue, and a better understanding of neutrophil-dengue biology is urgently needed.

Febrile Phase Soluble Urokinase Plasminogen Activator Receptor and Olfactomedin 4 as Prognostic Biomarkers for Severe Dengue in Adults.

BACKGROUND: Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. METHODS: We prospectively enrolled 99 adults with dengue-40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. RESULTS: The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P < .001), critical (P < .001), and recovery (P = .005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P = .04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. CONCLUSIONS: In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase.

Variant-specific IgA protects against Omicron infection.

BACKGROUND: The emergence of rapidly evolving SARS-CoV-2 variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. METHODS: We examined two prospective cohorts of mRNA-vaccinated-and-boosted individuals during the Omicron wave of infection in Singapore. RESULTS: We found that, individuals, who remain uninfected over the follow-up period, had a higher variant-specific IgA, but not IgG, antibody response at 1-month post booster vaccination, compared with individuals who became infected. CONCLUSIONS: We conclude that IgA may have a potential contributory role in protection against Omicron infection.

Correction: Understanding antibody-dependent enhancement in dengue: Are afucosylated IgG1s a concern?

[This corrects the article DOI: 10.1371/journal.ppat.1011223.].

Myeloperoxidase inhibition may protect against endothelial glycocalyx shedding induced by COVID-19 plasma.

BACKGROUND: SARS-CoV-2, the causative agent of COVID-19, is a threat to public health. Evidence suggests increased neutrophil activation and endothelial glycocalyx (EG) damage are independently associated with severe COVID-19. Here, we hypothesised that an increased level of blood neutrophil myeloperoxidase (MPO) is associated with soluble EG breakdown, and inhibiting MPO activity may reduce EG damage. METHODS: Analysing a subset of acute and convalescent COVID-19 plasma, 10 from severe and 15 from non-severe COVID-19 cases, and 9 from pre-COVID-19 controls, we determined MPO levels, MPO activity and soluble EG proteins (syndecan-1 and glypican-1) levels by enzyme-linked immunosorbent assay. In vitro primary human aortic endothelial cells were cultured with plasma untreated or treated with specific MPO inhibitors (MPO-IN-28, AZD5904) to determine EG shedding. We then investigated whether inhibiting MPO activity decreased EG degradation. RESULTS: In COVID-19 plasma, MPO levels, MPO activity and levels of soluble EG proteins are significantly raised compared to controls, and concentrations increase in proportion to disease severity. Despite clinical recovery, protein concentrations remain significantly elevated. Interestingly, there is a trend of increasing MPO activity in convalescent plasma in both severe and non-severe groups. MPO levels and MPO activity correlate significantly with soluble EG levels and inhibiting MPO activity leads to reduced syndecan-1 shedding, in vitro. CONCLUSIONS: Neutrophil MPO may increase EG shedding in COVID-19, and inhibiting MPO activity may protect against EG degradation. Further research is needed to evaluate the utility of MPO inhibitors as potential therapeutics against severe COVID-19.

COVID-19 can result in severe disease and is potentially fatal. Neutrophils, the most abundant white blood cells in circulation, secrete antimicrobials that have been linked to severe COVID-19 development. The endothelial glycocalyx (EG) is a carbohydrate rich layer that coats the inner surface of the vasculature and damage to the EG is observed in severe COVID-19. Here, we investigate whether myeloperoxidase, an antimicrobial released by neutrophils, is associated with EG damage in COVID-19 patients. We also determine whether reducing myeloperoxidase activity prevents damage to the EG. Our results suggest myeloperoxidase is associated with EG damage and severe COVID-19. We also demonstrated that a reduction in myeloperoxidase activity may protect against EG degradation. Further studies to evaluate the utility of MPO inhibitors as a therapy against severe COVID-19 are warranted.

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

Conserved longitudinal alterations of anti-S-protein IgG subclasses in disease progression in initial ancestral Wuhan and vaccine breakthrough Delta infections.

Introduction: COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods: Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results: We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion: While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

The Omicron-transformer: Rise of the subvariants in the age of vaccines.

INTRODUCTION: Omicron is the latest SARS-CoV-2 variant of concern, the pathogen that causes COVID-19. Since its emergence in late 2021, Omicron has displaced other circulating variants and caused successive waves of infection worldwide throughout 2022. Omicron is characterised by the rapid emergence of many subvariants and high rates of infection in people with vaccine- and/or infection induced immunity. This review article will consolidate current knowledge regarding Omicron subvariants, the role of boosters, and future vaccine development. METHOD: This narrative review is based on a literature search using PubMed. Search terms related to Omicron were used and priority was given to published peer-reviewed articles over pre-prints. RESULTS: Studies indicate that vaccinations and boosters are important to reduce disease severity, hospitalisation, and death from Omicron. A variety of factors, such as differing host factors, circulating variants, and forces of infection, can influence the benefit of repeated booster administration. Next-generation bivalent vaccines have now been approved in some countries including Singapore and have demonstrated the ability to induce broad variant protection. Future third-generation vaccines involving mucosal vaccines and/or pan-sarbecovirus vaccines may provide broader and longer-lasting protection. CONCLUSION: Due to current high levels of vaccine- and infection-induced immunity, it is likely that rates of severe illness, hospitalisation, and death due to Omicron will continue to moderate. Nevertheless, the virus is ever-changing, and public health policies, especially those related to vaccinations, will also have to continually evolve and adapt as COVID-19 transitions to endemicity.

Association of Neutrophil Mediators With Dengue Disease Severity and Cardiac Impairment in Adults.

BACKGROUND: Cardiac impairment contributes to hypotension in severe dengue (SD). However, studies examining pathogenic factors affecting dengue-associated cardiac impairment are lacking. We examined the role of neutrophil mediators on cardiac impairment in clinical dengue. METHODS: We prospectively enrolled adult patients with dengue and controls. Cardiac parameters were measured using a bioimpedance device. Neutrophils mediators were measured, including myeloperoxidase (MPO) and citrullinated histone H3. RESULTS: We recruited 107 dengue patients and 30 controls. Patients with dengue were classified according to World Health Organization 2009 guidelines (44 with dengue fever [DF], 51 with DF with warning signs, and 12 with SD). During critical phase, stroke index (P < .001), cardiac index (P = .03), and Granov-Goor index (P < .001) were significantly lower in patients with dengue than in controls. During critical phase, MPO was significantly higher in patients with dengue than in controls (P < .001) and also significantly higher in patients with SD than in those with DF. In addition, MPO was inversely associated with the stroke, cardiac, and Granov-Goor indexes, during the critical phase, and longitudinally as well. CONCLUSIONS: Cardiac function was decreased, and MPO increased, during with critical phase in patients SD compared with those with DF and controls. MPO may mediate dengue-associated cardiac impairment.

Clinical and prognostic relevance of sST2 in adults with dengue-associated cardiac impairment and severe dengue.

BACKGROUND: Dengue can be complicated by severe outcomes including cardiac impairment, and the lack of reliable prognostic biomarkers poses a challenge in managing febrile dengue patients. Here, we investigated the functionality of soluble suppressor of tumorigenicity (sST2) as a predictive marker of severe dengue and its association in dengue-associated cardiac impairment. METHODS: Plasma samples, aged >16 years, collected from 36 dengue fever, 43 dengue with warning signs, 11 severe dengue (collected at febrile, critical and recovery phases) and 30 controls were assayed for plasma levels of sST2, troponin T and N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) by ELISA. Cardiac parameters: stroke index (SI), cardiac index (CI) and Granov-Goor Index (GGI) were measured with a bioimpedance device during the different phases for dengue subjects and once for the controls. PRINCIPAL FINDINGS: In the febrile, critical and early recovery phases, sST2 levels were significantly elevated in dengue participants and sST2 levels increased with increasing disease severity (P < 0.01 for all). sST2 concentrations were negatively correlated with SI (r = -0.48; P < 0.001, r = -0.55; P < 0.001), CI (r = -0.26; P = 0.02, r = -0.6: P < 0.001) and GGI (r = -0.44; P < 0.001, r = -0.57; P < 0.001) in the critical and early recovery phases. In contrast, sST2 levels in the febrile and critical phases, were positive correlated to troponin T (r = 0.44, P < 0.001; r = 0.22, P = 0.03, respectively) and NT-proBNP (r = 0.21, P = 0.03; r = 0.35, P < 0.001). ROC analysis demonstrated sST2 as a good biomarker of severe dengue in the critical phase, AUROC 0.79, P < 0.001. CONCLUSION/SIGNIFICANCE: sST2 levels were elevated in patients with dengue especially in cases of severe dengue. Furthermore, increased sST2 levels were associated with cardiac indicators suggesting lower cardiac performance. While further research is needed to demonstrate its clinical utility, sST2 may be a useful prognostic biomarker of severe dengue.

Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC].

BACKGROUND: Over 2021, COVID-19 vaccination programs worldwide focused on raising population immunity through the primary COVID-19 vaccine series. In Singapore, two mRNA vaccines (BNT162b2 and mRNA-1273) and the inactivated vaccine CoronaVac are currently authorized under the National Vaccination Programme for use as the primary vaccination series. More than 90% of the Singapore population has received at least one dose of a COVID-19 vaccine as of December 2021. With the demonstration that vaccine effectiveness wanes in the months after vaccination, and the emergence of Omicron which evades host immunity from prior infection and/or vaccination, attention in many countries has shifted to how best to maintain immunity through booster vaccinations. METHODS: The objectives of this phase 3, randomized, subject-blinded, controlled clinical trial are to assess the safety and immunogenicity of heterologous boost COVID-19 vaccine regimens (intervention groups 1-4) compared with a homologous boost regimen (control arm) in up to 600 adult volunteers. As non-mRNA vaccine candidates may enter the study at different time points depending on vaccine availability and local regulatory approval, participants will be randomized at equal probability to the available intervention arms at the time of randomization. Eligible participants will have received two doses of a homologous mRNA vaccine series with BNT162b2 or mRNA-1273 at least 6 months prior to enrolment. Participants will be excluded if they have a history of confirmed SARS or SARS-CoV-2 infection, are immunocompromised, or are pregnant. Participants will be monitored for adverse events and serious adverse events by physical examinations, laboratory tests and self-reporting. Blood samples will be collected at serial time points [pre-vaccination/screening (day - 14 to day 0), day 7, day 28, day 180, day 360 post-vaccination] for assessment of antibody and cellular immune parameters. Primary endpoint is the level of anti-SARS-CoV-2 spike immunoglobulins at day 28 post-booster and will be measured against wildtype SARS-CoV-2 and variants of concern. Comprehensive immune profiling of the humoral and cellular immune response to vaccination will be performed. DISCUSSION: This study will provide necessary data to understand the quantity, quality, and persistence of the immune response to a homologous and heterologous third booster dose of COVID-19 vaccines. This is an important step in developing COVID-19 vaccination programs beyond the primary series. TRIAL REGISTRATION: ClinicalTrials.gov NCT05142319 . Registered on 2 Dec 2021.

Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial.

BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.

Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications for infection control: a review.

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.

Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum ß-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum ß-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta).

BACKGROUND: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. METHODS: National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. RESULTS: A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). CONCLUSIONS: B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.