COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study).

BACKGROUND: Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis.

BACKGROUND: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. METHODS: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity. RESULTS: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third-46.0%, fourth-44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9-9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection. CONCLUSIONS: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses.

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study.

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report.

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Safeguarding equitable HIV service delivery at the health facility-level in a resource-limited setting during the pandemic.

The COVID-19 pandemic had a severe impact on delivering essential health services, including HIV service delivery. Among the challenges encountered and addressed by the HIV and AIDS Department of the San Lazaro Hospital were ensuring continued access to antiretroviral therapy and ensuring continuity of client education and empowerment. Two years into the pandemic, challenges still ensue, such as protecting health care providers from COVID-19 and regular clinical monitoring of clients. This highlights the importance of urgent action to strengthen the resilience of health systems at all its levels, not only to respond to sudden disturbances, but also to transform and evolve to be able to better face future pandemics.

Severe Anemia Due to Cold Agglutinin Syndrome in a COVID-19 Patient with IgM Monoclonal Gammopathy of Undetermined Significance Successfully Treated with Corticosteroids.

Secondary cold agglutinin syndrome (CAS) is autoimmune hemolytic anemia secondary to infections and lymphoid disorder. We here report the first Asian case of CAS secondary to novel coronavirus disease 2019 (COVID-19). A 72-year-old Japanese woman presented with a 2-week history of dyspnea and cough, and laboratory data revealed severe hemolytic anemia with a hemoglobin level of 4.7 g/dL. She was diagnosed with COVID-19, CAS, and monoclonal gammopathy of undetermined significance (MGUS). The anemia responded to corticosteroids administered for COVID-19 and required maintenance therapy. Although corticosteroids are not a standard therapy for CAS, they might be effective for CAS secondary to COVID-19 complicated with MGUS.

Social and Behavioral Factors Associated with Lack of Intent to Receive COVID-19 Vaccine, Japan.

Persons in Japan who did not intend to receive COVID-19 vaccines after widespread rollout were less likely than others to engage in preventive measures or to be afraid of getting infected or infecting others. They were also not less likely to engage in potentially high-risk behaviors, suggesting similar or higher exposure risks.

Behavioral factors associated with SARS-CoV-2 infection in Japan.

BACKGROUND: The relative burden of COVID-19 has been less severe in Japan. One reason for this may be the uniquely strict restrictions imposed upon bars/restaurants. To assess if this approach was appropriately targeting high-risk individuals, we examined behavioral factors associated with SARS-CoV-2 infection in the community. METHODS: This multicenter case-control study involved individuals receiving SARS-CoV-2 testing in June-August 2021. Behavioral exposures in the past 2 weeks were collected via questionnaire. SARS-CoV-2 PCR-positive individuals were cases, while PCR-negative individuals were controls. RESULTS: The analysis included 778 individuals (266 [34.2%] positives; median age [interquartile range] 33 [27-43] years). Attending three or more social gatherings was associated with SARS-CoV-2 infection (adjusted odds ratio [aOR] 2.00 [95% CI 1.31-3.05]). Attending gatherings with alcohol (aOR 2.29 [1.53-3.42]), at bars/restaurants (aOR 1.55 [1.04-2.30]), outdoors/at parks (aOR 2.87 [1.01-8.13]), at night (aOR 2.07 [1.40-3.04]), five or more people (aOR 1.81 [1.00-3.30]), 2 hours or longer (aOR 1.76 [1.14-2.71]), not wearing a mask during gatherings (aOR 4.18 [2.29-7.64]), and cloth mask use (aOR 1.77 [1.11-2.83]) were associated with infection. Going to karaoke (aOR 2.53 [1.25-5.09]) and to a gym (aOR 1.87 [1.11-3.16]) were also associated with infection. Factors not associated with infection included visiting a cafe with others, ordering takeout, using food delivery services, eating out by oneself, and work/school/travel-related exposures including teleworking. CONCLUSIONS: We identified multiple behavioral factors associated with SARS-CoV-2 infection, many of which were in line with the policy/risk communication implemented in Japan. Rapid assessment of risk factors can inform decision making.

Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to almost every region and country in the world, leading to widespread travel restrictions and national lockdowns. Currently, there are limited epidemiological and clinical data on COVID-19 patients from low and middle-income countries. We conducted a retrospective single-center study of the first 100 individuals with suspected COVID-19 (between Jan. 25 and Mar. 29, 2020) admitted to San Lazaro Hospital (SLH), the national infectious diseases referral hospital in Manila, Philippines. RESULTS: Demographic data, travel history, clinical features, and outcomes were summarized and compared between COVID-19 confirmed and non-confirmed cases. The first two confirmed cases were Chinese nationals, admitted on Jan. 25. The third confirmed case was a Filipino, admitted on Mar. 8. Trends toward confirmed COVID-19 cases not reporting international travel and being admitted to SLH from the densely populated area of Manila city were observed during Mar. 8-29. All 42 of the 100 confirmed COVID-19 cases were adults, 40% were aged 60 years and above and 55% were male. Three were health workers. Among individuals with suspected COVID-19, confirmed cases were more likely to be older, Filipino, not report international travel history and have at least one underlying disease, particularly diabetes, report difficulty in breathing, and a longer duration of symptoms. In over 90% of non-COVID-19 cases, the alternative diagnosis was respiratory. Nine (21%) confirmed cases died. The median duration from symptoms onset to death was 11.5 (range: 8-18) days. CONCLUSIONS: Imported COVID-19 cases have reduced but local transmission persists and there is a trend toward cases being admitted to SLH from densely populated areas. This study highlights the difficulty in diagnosing COVID-19 on clinical grounds and the importance of diagnostic capacity in all settings. Difficulty of breathing was the only symptom associated with COVID-19 infection and should alert clinicians to the possibility of COVID-19. Clinical characteristics of confirmed COVID-19 cases and a hospital case fatality rate of 21% are comparable with other settings.

Performance of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients: A retrospective study in outbreak on a cruise ship.

OBJECTIVES: A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients. METHODS: Blood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a follow-up SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to confirm which antibodies were influenced on LFA- and ECLIA- false-negative result in crew-member samples. RESULTS: Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. All antibody titers measured using ELISA were significantly lower in blood samples with negative results than in those with positive results in both LFA and ECLIA. In the patients with negative results from the follow-up genetic testing, IgM-, IgG-, and total-antibody positivity rates were 22.9%, 47.6%, and 72.4%, respectively. CONCLUSIONS: These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines.

Costing analysis of field implementation of hepatitis C case detection in rural Maung Russey operational district, Cambodia.

BACKGROUND: When a new health programme is introduced, it is crucial to estimate the costs for rational health policy decision-making. The aim of this study was to determine the costs of implementing two strategies for hepatitis C virus (HCV) screening in rural Cambodia. METHODS: We retrospectively analysed clinical and cost data that were collected routinely for a demonstration project for scaling up HCV screening and testing in Cambodia. The programme data were collected between March and December 2018 in Maung Russey operational district in Battambang Province, Cambodia. FINDINGS: During the study period, 24 230 people were screened; 1194 (5%) were HCV seropositive, of whom 793 (66%) were confirmed to be viraemic. During the study period, 18% of the estimated population of the operational district were screened, of whom 45% were estimated to be seropositive and 41% to be viraemic. With passive screening alone, 8% of the estimated population were screened, of whom 29% were estimated to be seropositive and 28% viraemic. The cost per detected viraemic case was US$ 194 for passive screening alone and US$ 283 for passive and active screening combined. Labour costs (31%) and tests and materials (29%) comprised the largest proportions of the cost. CONCLUSION: Combined active and passive screening per viraemic case detected was US$ 89 more expensive than passive screening alone but provided a higher yield (41% versus 28%) of viraemic cases. Therefore, adding active screening to passive screening is beneficial. Selective active screening strategies, such as targeting people over 45 years and other higher-risk groups, added value for HCV diagnosis.

Correction to: First COVID-19 infections in the Philippines: a case report.

[This corrects the article DOI: 10.1186/s41182-020-00203-0.].

Epidemiological and clinical characteristics of the first 500 confirmed COVID-19 inpatients in a tertiary infectious disease referral hospital in Manila, Philippines.

BACKGROUND: The Philippines has been one of the most affected COVID-19 countries in the Western Pacific region, but there are limited data on COVID-19-related mortality and associated factors from this setting. We aimed to describe the epidemiological and clinical characteristics and associations with mortality among COVID-19-confirmed individuals admitted to an infectious diseases referral hospital in Metro Manila. MAIN TEXT: This was a single-centre retrospective analysis including the first 500 laboratory-confirmed COVID-19 individuals admitted to San Lazaro Hospital, Metro Manila, Philippines, from January to October 2020. We extracted clinical data and examined epidemiological and clinical characteristics and factors associated with in-hospital mortality. Of the 500 individuals, 133 (26.6%) were healthcare workers (HCW) and 367 (73.4%) were non-HCW, with HCW more likely presenting with milder symptoms. Non-HCW admissions were more likely to have at least one underlying disease (51.6% vs. 40.0%; p = 0.002), with hypertension (35.4%), diabetes (17.4%), and tuberculosis (8.2%) being the most common. Sixty-one (12.2%) died, comprising 1 HCW and 60 non-HCW (0.7% vs. 16.3%; p < 0.001). Among the non-HCW, no death occurred for the 0-10 years age group, but deaths were recorded across all other age groups. Compared to those who recovered, individuals who died were more likely to be older (p < 0.001), male (p = 0.015), report difficulty of breathing (p < 0.001), be HIV positive (p = 0.008), be intubated (p < 0.001), categorised as severe or critical (p < 0.001), have a shorter mean hospital stay (p < 0.001), or have an additional diagnosis of pneumonia (p < 0.001) or ARDS (p < 0.001). CONCLUSION: Our analysis reflected significant differences in characteristics, symptomatology, and outcomes between healthcare and non-healthcare workers. Despite the unique mix of cohorts, our results support the country's national guideline on COVID-19 vaccination which prioritises healthcare workers, the elderly, and people with comorbidities and immunodeficiency states.

Detection of SARS-CoV-2 using qRT-PCR in saliva obtained from asymptomatic or mild COVID-19 patients, comparative analysis with matched nasopharyngeal samples.

OBJECTIVES: The accurate detection of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is essential for the diagnosis of coronavirus disease 2019 (COVID-19). We compared the quantitative RT-PCR results between nasopharyngeal swabs and saliva specimens. METHODS: A COVID-19 outbreak occurred on a cruise ship at Nagasaki port, Japan. We obtained 123 nasopharyngeal swabs and saliva each from asymptomatic or mild patients in the late phase of infection. RESULTS: The intervals from the diagnosis to the sampling were 25.5 days for nasopharyngeal swabs and 28.9 days for saliva. The positive rate was 19.5% (24/123) for nasopharyngeal swabs and 38.2% (47/123) for saliva (P = 0.48). The quantified viral copies (mean ± SEM copies/5 µl) were 9.3±2.6 in nasopharyngeal swabs and 920±850 in saliva (P = 0.0006). CONCLUSIONS: The advantages of saliva specimens include positive rate improvement and accurate viral load detection. Saliva may be used as a reliable sample for SARS-CoV-2 detection.

If Not COVID-19 What Is It? Analysis of COVID-19 versus Common Respiratory Viruses among Symptomatic Health Care Workers in a Tertiary Infectious Disease Referral Hospital in Manila, Philippines.

The COVID-19 global pandemic is entering its second year. In this short report we present additional results as a supplement to our previous paper on COVID-19 and common respiratory virus screening for healthcare workers (HCWs) in a tertiary infectious disease referral hospital in Manila, Philippines. We sought to understand what etiologic agents could explain the upper/lower respiratory tract infection-like (URTI/LRTI-like) symptoms exhibited by 88% of the 324 HCWs tested. Among the patients who had URTI/LRTI-like symptoms, only seven (2%) were positive for COVID-19, while 38 (13%) of the symptomatic participants were identified positive for another viral etiologic agent. Rhinovirus was the most common infection, with 21 (9%) of the symptomatic participants positive for rhinovirus. Based on these results, testing symptomatic HCWs for common respiratory illnesses in addition to COVID-19 should be considered during this time of global pandemic.