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1.
Clin Transl Immunology ; 11(5): e1384, 2022.
Article in English | MEDLINE | ID: covidwho-1849495

ABSTRACT

Objectives: Immunopathology of ongoing COVID-19 global pandemic is not limited solely to pulmonary tissue, but is often associated with multi-organ complications, mechanisms of which are intensely being investigated. In this regard, the interplay between immune, stromal cells and cytokines in pulmonary and extrapulmonary infected tissues, especially in young adults (median age 46 years, range 30-53 years) without comorbidities, remains poorly characterised. Methods: We profiled lung, heart and intestinal autopsy samples from five SARS-CoV-2-infected cases for 18-20 targets to detect immune, cytokine and stromal cell status at subcellular resolution by a novel IHC-based deep-phenotyping technique, iSPOT (immunoSpatial histoPhenOmics using TSA-IHC), to assess spatial and functional patterns of immune response in situ, in lethal COVID-19 infection. Results: SARS-CoV-2-infected autopsy samples exhibit skewed counts of immune populations in all samples with organ-specific dysfunctions. Lung and ileal tissue reveal altered architecture with marked loss of tissue integrity, while lung and heart tissue show severe hyperinflammation marked by elevated TNF-α in heart tissue and additionally IL-6, IFN-γ and IL-10 cytokines in lung samples. Conclusion: With resurgence of infection in younger populations, single-cell cytokine localisation in immune and stromal structures provides important mechanistic insights into organ-specific immunopathology of naïve SARS-CoV-2 infection in the absence of other comorbidities.

2.
Antibiotics (Basel) ; 11(3)2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1731895

ABSTRACT

Data on use of monoclonal antibodies (mAbs) in hospitalized patients are limited. In this cross-sectional study, we evaluated the use of mAbs for early treatment of unvaccinated hospitalized patients with mild-to-moderate COVID-19. All inpatients at our center were screened on 27 October 2021. Primary outcome was in-hospital deterioration as defined by a composite of oxygen requirement, intensive care unit (ICU) admission, or mortality within 28 days of admission. Ninety-four out of 410 COVID-19 inpatients were included in the final analysis, of whom 19 (20.2%) received early treatment with sotrovimab. The median age was 73 years (IQR 61-83), and 35 (37.2%) were female. Although the treatment group was significantly older and had more comorbidities, there was a lower proportion of progression to oxygen requirement (31.6% vs. 54.7%), ICU admission (10.5% vs. 24.0%), or mortality (5.3% vs. 13.3%). Kaplan-Meier curves showed a significant difference in time to in-hospital deterioration (log-rank test, p = 0.043). Cox proportional hazards model for in-hospital deterioration showed that sotrovimab treatment was protective (hazard ratio, 0.41; 95% CI, 0.17-0.99; p = 0.047) after adjustment for baseline ISARIC deterioration score. Our findings support the use of sotrovimab for early treatment in hospitalized patients with mild-to-moderate COVID-19 at a high risk of disease progression.

3.
Clin Infect Dis ; 74(7): 1260-1264, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1702505

ABSTRACT

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Clinical Trials as Topic , Humans , Respiration, Artificial , SARS-CoV-2
5.
Antibiotics (Basel) ; 11(2)2022 Jan 31.
Article in English | MEDLINE | ID: covidwho-1667025

ABSTRACT

BACKGROUND: COVID-19 imposes challenges in antibiotic decision-making due to similarities between bacterial pneumonia and moderate to severe COVID-19. We evaluated the effects of antibiotic therapy on the clinical outcomes of COVID-19 pneumonia patients and diagnostic accuracy of key inflammatory markers to inform antibiotic decision-making. METHODS: An observational cohort study was conducted in patients hospitalised with COVID-19 at the National Centre for Infectious Diseases and Tan Tock Seng Hospital, Singapore, from January to April 2020. Patients were defined as receiving empiric antibiotic treatment for COVID-19 if started within 3 days of diagnosis. RESULTS: Of 717 patients included, 86 (12.0%) were treated with antibiotics and 26 (3.6%) had documented bacterial infections. Among 278 patients with COVID-19 pneumonia, those treated with antibiotics had more diarrhoea (26, 34.7% vs. 24, 11.8%, p < 0.01), while subsequent admissions to the intensive care unit were not lower (6, 8.0% vs. 10, 4.9% p = 0.384). Antibiotic treatment was not independently associated with lower 30-day (adjusted odds ratio, aOR 19.528, 95% confidence interval, CI 1.039-367.021) or in-hospital mortality (aOR 3.870, 95% CI 0.433-34.625) rates after adjusting for age, co-morbidities and severity of COVID-19 illness. Compared to white cell count and procalcitonin level, the C-reactive protein level had the best diagnostic accuracy for documented bacterial infections (area under the curve, AUC of 0.822). However, the sensitivity and specificity were less than 90%. CONCLUSION: Empiric antibiotic use in those presenting with COVID-19 pneumonia did not prevent deterioration or mortality. More studies are needed to evaluate strategies to diagnose bacterial co-infections in these patients.

6.
EMBO Mol Med ; 14(3): e15227, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1643965

ABSTRACT

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1ß and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.


Subject(s)
COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2
7.
J Clin Immunol ; 42(2): 214-229, 2022 02.
Article in English | MEDLINE | ID: covidwho-1544509

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Cytokines/immunology , Host-Pathogen Interactions/immunology , Humans , Inflammation/immunology , Mutation/immunology , Pandemics/prevention & control , T-Lymphocytes/immunology
8.
NPJ Vaccines ; 6(1): 125, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1483131

ABSTRACT

The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence.

9.
J Clin Invest ; 131(17)2021 09 01.
Article in English | MEDLINE | ID: covidwho-1463086

ABSTRACT

Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein-specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1-convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike-specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 , Immunity, Cellular/drug effects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Adult , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
12.
N Engl J Med ; 385(15): 1401-1406, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1361670

ABSTRACT

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy. (Funded by the Singapore National Research Foundation and National Medical Research Council.).


Subject(s)
Antibodies, Viral/blood , Broadly Neutralizing Antibodies/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/immunology , B-Lymphocytes , Humans , Immunogenicity, Vaccine , Phylogeny , SARS Virus/genetics , SARS-CoV-2/genetics , Survivors
13.
Clin Infect Dis ; 74(7): 1260-1264, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1352150

ABSTRACT

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Clinical Trials as Topic , Humans , Respiration, Artificial , SARS-CoV-2
14.
Sci Rep ; 11(1): 7477, 2021 04 05.
Article in English | MEDLINE | ID: covidwho-1169408

ABSTRACT

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24-6.47) and neutrophil count (aOR 2.39, 95% CI 1.34-4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828-0.979). Median APACHE II score was 19 (IQR 17-22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89-129). Median peak FiO2 was 0.75 (IQR 0.6-1.0), positive end-expiratory pressure 12 (IQR 10-14) and plateau pressure 22 (IQR 18-26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5-13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.


Subject(s)
COVID-19/pathology , Adult , Area Under Curve , C-Reactive Protein/metabolism , COVID-19/virology , Dyspnea/etiology , Female , Humans , Intensive Care Units , L-Lactate Dehydrogenase/metabolism , Logistic Models , Male , Middle Aged , Neutrophils/cytology , Prospective Studies , ROC Curve , Respiration, Artificial , Respiratory Rate , SARS-CoV-2/isolation & purification , Severity of Illness Index , Singapore
15.
Elife ; 102021 03 23.
Article in English | MEDLINE | ID: covidwho-1146275

ABSTRACT

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/etiology , Endothelium, Vascular/pathology , Lymphocyte Activation , Adult , Aged , COVID-19/immunology , COVID-19/pathology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/pathology , Cytokines/immunology , Endothelial Cells/immunology , Endothelial Cells/pathology , Endothelium, Vascular/immunology , Female , Humans , Male , Middle Aged , Risk Factors
16.
Clin Transl Immunology ; 10(2): e1241, 2021.
Article in English | MEDLINE | ID: covidwho-1095258

ABSTRACT

OBJECTIVES: The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralise against the G614 variant. METHODS: Antibody profiling against the SARS-CoV-2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS-CoV-2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID-19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). RESULTS: Profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. CONCLUSIONS: Cross-reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS-CoV-2. More importantly, there should be negligible impact towards the efficacy of antibody-based therapies and vaccines that are currently being developed.

17.
Cell Rep Med ; 2(2): 100193, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1069040

ABSTRACT

Early detection of infection is crucial to limit the spread of coronavirus disease 2019 (COVID-19). Here we develop a flow cytometry-based assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antibodies in individuals with COVID-19. The assay detects specific immunoglobulin M (IgM), IgA, and IgG in individuals with COVID-19 and also acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of infection. Furthermore, asymptomatic individuals with COVID-19 also develop specific IgM, IgA, and IgG, with IgG1 being the most dominant subclass. Although the antibody levels are lower in asymptomatic infection, the assay is highly sensitive and detects 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic and asymptomatic infections, which may otherwise remain undetected.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Immunoglobulin Class Switching/physiology , Immunoglobulin G/blood , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Asymptomatic Diseases , COVID-19/immunology , COVID-19/virology , Flow Cytometry , Humans , Immunoglobulin G/immunology , Immunologic Tests/methods , SARS-CoV-2/isolation & purification
18.
Antimicrob Resist Infect Control ; 10(1): 28, 2021 02 03.
Article in English | MEDLINE | ID: covidwho-1063200

ABSTRACT

BACKGROUND: The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing. METHODS: One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017-2019. RESULTS: The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p = 0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p < 0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p = 0.08). CONCLUSION: During the COVID-19 pandemic, there was no increase in antimicrobial prescribing and no significant differences in antimicrobial prescribing quality indicators.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Drug Prescriptions , SARS-CoV-2 , Anti-Bacterial Agents/administration & dosage , Antimicrobial Stewardship/statistics & numerical data , Humans , Inappropriate Prescribing/statistics & numerical data , Singapore/epidemiology , Tertiary Care Centers
19.
Nat Biotechnol ; 38(9): 1073-1078, 2020 09.
Article in English | MEDLINE | ID: covidwho-1023948

ABSTRACT

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2 , Antibodies/immunology , Antibodies/pharmacology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Neutralization Tests , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Interaction Domains and Motifs/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
20.
Ann Acad Med Singap ; 49(11): 857-869, 2020 11.
Article in English | MEDLINE | ID: covidwho-1001259

ABSTRACT

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION: The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.


Subject(s)
COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , Abortion, Spontaneous/epidemiology , Adult , COVID-19/physiopathology , COVID-19/transmission , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cohort Studies , Disease Transmission, Infectious/statistics & numerical data , Female , Fetal Blood/immunology , Humans , Infectious Disease Transmission, Vertical/statistics & numerical data , Live Birth/epidemiology , Maternal Age , Milk, Human/chemistry , Milk, Human/virology , Obesity, Maternal/epidemiology , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prospective Studies , RNA, Viral/analysis , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Singapore/epidemiology , Umbilical Cord/pathology , Young Adult
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