Economic Evaluation of Evusheld for Preexposure Prevention of COVID-19 in High-Risk Populations: Early Evidence from Thailand.

BACKGROUND AND AIMS: The introduction of Coronavirus disease 2019 (COVID-19) vaccines urged all Thais to seek prevention of serious illness and death from COVID-19. However, immunocompromised individuals might not be able to achieve an efficient immune response from these vaccines. This study aimed to evaluate the cost-effectiveness and budget impact of introducing Evusheld (tixagevimab plus cilgavimab) for three patient groups-organ transplant, autoimmune disease, and dialysis patients, from the Thai government perspective. METHODS: A Markov decision model was developed to compare the use of Evusheld plus COVID-19 vaccines versus COVID-19 vaccines alone. The methodology followed the National HTA Guidelines of Thailand. Model input parameters were collected locally from retrospective data and from a literature review. RESULTS: Evusheld helped prevent COVID-19 infection, severe infection, and death in all three patient groups. Using the Thai threshold of 160,000 Thai Baht (THB) per quality-adjusted life year (QALY) gained, the only scenario found to be cost-effective was that of dialysis patients with inadequate immune response, with an incremental cost-effectiveness ratio (ICER) of 54,700 THB per QALY gained. To make a policy of Evusheld provision cost-effective in other groups, the price of Evusheld had to be lower (a reduction of 44-88% of its current price). The results of one-way sensitivity analysis indicated that the cost-effectiveness of Evusheld was sensitive to changes in the rate of infection, cost and efficacy of Evusheld, proportion of inadequate immune responses, and the probability of moving from a 'recovered' to 'susceptible' status. CONCLUSION: Among three COVID-19-vaccinated immunocompromised patient populations, this study concluded that Evusheld was cost-effective for dialysis patients with inadequate immune response to the COVID-19 vaccine.

Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients.

Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule, especially in resource-limited settings. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 over time in a cohort of patients who were previously infected with the wild-type SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of wild-type SARS-CoV-2 infection were enrolled in our immunological study. Blood samples were collected at 3-, 6-, 9-, and 12-months post symptom onset or detection of SARS-CoV-2 by RT-PCR (in asymptomatic individuals). The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. We observed a high level of correlation between neutralizing and SARS-CoV-2 spike protein-specific antibody titers. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5-327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time in both participants with severe disease and mild disease were depended on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

The impact of COVID-19 and control measures on public health in Thailand, 2020.

BACKGROUND: The COVID-19 virus has been an emerging disease causing global outbreaks for over a year. In Thailand, transmission may be controlled by strict measures that could positively and negatively impact physical health and suicidal behavior. METHODS: The incidence of COVID-19 was retrieved from the Department of Disease Control (DDC). The impact of viral diseases was retrieved from the open-source of the DDC and King Chulalongkorn Memorial Hospital. The road accidents data were from the Thai Ministry of Transport. The suicidal behavior data were obtained from the Department of Mental Health. We compared data from the year 2019 with the pandemic COVID-19 outbreak period in 2020, before lockdown, during lockdown, easing, and new wave period using unpaired t-test and least-squares linear regression. We compared the impact of the outbreak on various data records in 2020 with corresponding non-outbreak from 2019. RESULTS: There was a significant decline in cases of influenza (p < 0.001) and norovirus (p = 0.01). However, there was no significant difference in RSV cases (p = 0.17). There was a dramatic increase in attempt to suicides and suicides (p < 0.001). There was no impact on roadside accidents and outpatient department visits. DISCUSSION: The extensive intervention measures during lockdown during the first wave positively impacted total cases for each period for acute respiratory and gastrointestinal tract diseases, car accidents, and injuries and negatively impacted indicators of suicidal behavior. The data support government policies that would be effective against the next outbreak by promoting the "new normal" lifestyle.

Long-term specific IgG response to SARS-CoV-2 nucleocapsid protein in recovered COVID-19 patients.

This study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N = 302) or multiple time points (N = 229) 3-12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months (P < 0.01) and was higher in the pneumonia group than in the non-pneumonia/asymptomatic group at 6 months (P < 0.01), 9 months (P = 0.04), and 12 months (P = 0.04). The rate started to decline 6-12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r = 0.192, P < 0.01) but negatively correlated with interval between symptom onset and blood sampling (r = - 0.567, P < 0.01). These findings can guide vaccine strategies in recovered COVID-19 patients.

T cell mediated immunity against influenza H5N1 nucleoprotein, matrix and hemagglutinin derived epitopes in H5N1 survivors and non-H5N1 subjects.

BACKGROUND: Protection against the influenza virus by a specific antibody is relatively strain specific; meanwhile broader immunity may be conferred by cell-mediated immune response to the conserved epitopes across influenza virus subtypes. A universal broad-spectrum influenza vaccine which confronts not only seasonal influenza virus, but also avian influenza H5N1 virus is promising. METHODS: This study determined the specific and cross-reactive T cell responses against the highly pathogenic avian influenza A (H5N1) virus in four survivors and 33 non-H5N1 subjects including 10 H3N2 patients and 23 healthy individuals. Ex vivo IFN-γ ELISpot assay using overlapping peptides spanning the entire nucleoprotein (NP), matrix (M) and hemagglutinin (HA) derived from A/Thailand/1(KAN-1)/2004 (H5N1) virus was employed in adjunct with flow cytometry for determining T cell functions. Microneutralization (microNT) assay was performed to determine the status of previous H5N1 virus infection. RESULTS: IFN-γ ELISpot assay demonstrated that survivors nos. 1 and 2 had markedly higher T cell responses against H5N1 NP, M and HA epitopes than survivors nos. 3 and 4; and the magnitude of T cell responses against NP were higher than that of M and HA. Durability of the immunoreactivity persisted for as long as four years after disease onset. Upon stimulation by NP in IFN-γ ELISpot assay, 60% of H3N2 patients and 39% of healthy subjects exhibited a cross-reactive T cell response. The higher frequency and magnitude of responses in H3N2 patients may be due to blood collection at the convalescent phase of the patients. In H5N1 survivors, the effector peptide-specific T cells generated from bulk culture PBMCs by in vitro stimulation displayed a polyfunction by simultaneously producing IFN-γ and TNF-α, together with upregulation of CD107a in recognition of the target cells pulsed with peptide or infected with rVac-NP virus as investigated by flow cytometry. CONCLUSIONS: This study provides an insight into the better understanding on the homosubtypic and heterosubtypic T cell-mediated immune responses in H5N1 survivors and non-H5N1 subjects. NP is an immunodominant target of cross-recognition owing to its high conservancy. Therefore, the development of vaccine targeting the conserved NP may be a novel strategy for influenza vaccine design.

Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020.

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread.

SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts, Thailand, April-June 2020.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although Thailand has been fairly effective at controlling the spread of COVID-19, continued disease surveillance and information on antibody response in recovered patients and their close contacts remain necessary in the absence of approved vaccines and antivirals. Here, we examined 217 recovered COVID-19 patients to assess their viral RNA shedding and residual antibodies against SARS-CoV-2. We also evaluated antibodies in blood samples from 308 close contacts of recovered COVID-19 patients. We found that viral RNA remained detectable in 6.6% of recovered COVID-19 cases and up to 105 days. IgM, IgG, and IgA antibodies against SARS-CoV-2 were detected in 13.8%, 88.5%, and 83.4% of the recovered cases 4-12 weeks after disease onset, respectively. Higher levels of antibodies detected were associated with severe illness patients experienced while hospitalized. Fifteen of the 308 contacts (4.9%) of COVID-19 cases tested positive for IgG antibodies, suggesting probable exposure. Viral clearance and the pattern of antibody responses in infected individuals are both crucial for effectively combating SARS-CoV-2. Our study provides additional information on the natural history of this newly emerging disease related to both natural host defenses and antibody duration.

Melioidosis in Thailand: Present and Future.

A recent modelling study estimated that there are 2800 deaths due to melioidosis in Thailand yearly. The Thailand Melioidosis Network (formed in 2012) has been working closely with the Ministry of Public Health (MoPH) to investigate and reduce the burden of this disease. Based on updated data, the incidence of melioidosis is still high in Northeast Thailand. More than 2000 culture-confirmed cases of melioidosis are diagnosed in general hospitals with microbiology laboratories in this region each year. The mortality rate is around 35%. Melioidosis is endemic throughout Thailand, but it is still not uncommon that microbiological facilities misidentify Burkholderia pseudomallei as a contaminant or another organism. Disease awareness is low, and people in rural areas neither wear boots nor boil water before drinking to protect themselves from acquiring B. pseudomallei. Previously, about 10 melioidosis deaths were formally reported to the National Notifiable Disease Surveillance System (Report 506) each year, thus limiting priority setting by the MoPH. In 2015, the formally reported number of melioidosis deaths rose to 112, solely because Sunpasithiprasong Hospital, Ubon Ratchathani province, reported its own data (n = 107). Melioidosis is truly an important cause of death in Thailand, and currently reported cases (Report 506) and cases diagnosed at research centers reflect the tip of the iceberg. Laboratory training and communication between clinicians and laboratory personnel are required to improve diagnosis and treatment of melioidosis countrywide. Implementation of rapid diagnostic tests, such as a lateral flow antigen detection assay, with high accuracy even in melioidosis-endemic countries such as Thailand, is critically needed. Reporting of all culture-confirmed melioidosis cases from every hospital with a microbiology laboratory, together with final outcome data, is mandated under the Communicable Diseases Act B.E.2558. By enforcing this legislation, the MoPH could raise the priority of this disease, and should consider implementing a campaign to raise awareness and melioidosis prevention countrywide.

Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses.

The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific.

Homosubtypic and heterosubtypic antibodies against highly pathogenic avian influenza H5N1 recombinant proteins in H5N1 survivors and non-H5N1 subjects.

Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus.

Activities of daily living associated with acquisition of melioidosis in northeast Thailand: a matched case-control study.

BACKGROUND: Melioidosis is a serious infectious disease caused by the Category B select agent and environmental saprophyte, Burkholderia pseudomallei. Most cases of naturally acquired infection are assumed to result from skin inoculation after exposure to soil or water. The aim of this study was to provide evidence for inoculation, inhalation and ingestion as routes of infection, and develop preventive guidelines based on this evidence. METHODS/PRINCIPAL FINDINGS: A prospective hospital-based 1∶2 matched case-control study was conducted in Northeast Thailand. Cases were patients with culture-confirmed melioidosis, and controls were patients admitted with non-infectious conditions during the same period, matched for gender, age, and diabetes mellitus. Activities of daily living were recorded for the 30-day period before onset of symptoms, and home visits were performed to obtain drinking water and culture this for B. pseudomallei. Multivariable conditional logistic regression analysis based on 286 cases and 512 controls showed that activities associated with a risk of melioidosis included working in a rice field (conditional odds ratio [cOR] = 2.1; 95% confidence interval [CI] 1.4-3.3), other activities associated with exposure to soil or water (cOR = 1.4; 95%CI 0.8-2.6), an open wound (cOR = 2.0; 95%CI 1.2-3.3), eating food contaminated with soil or dust (cOR = 1.5; 95%CI 1.0-2.2), drinking untreated water (cOR = 1.7; 95%CI 1.1-2.6), outdoor exposure to rain (cOR = 2.1; 95%CI 1.4-3.2), water inhalation (cOR = 2.4; 95%CI 1.5-3.9), current smoking (cOR = 1.5; 95%CI 1.0-2.3) and steroid intake (cOR = 3.1; 95%CI 1.4-6.9). B. pseudomallei was detected in water source(s) consumed by 7% of cases and 3% of controls (cOR = 2.2; 95%CI 0.8-5.8). CONCLUSIONS/SIGNIFICANCE: We used these findings to develop the first evidence-based guidelines for the prevention of melioidosis. These are suitable for people in melioidosis-endemic areas, travelers and military personnel. Public health campaigns based on our recommendations are under development in Thailand.

Biological properties of H5 hemagglutinin expressed by vaccinia virus vector and its immunological reactivity with human sera.

A recombinant vaccinia virus harboring the full length hemagglutinin (HA) gene derived from a highly pathogenic avian influenza A/Thailand/1(KAN-1)/2004 (H5N1) virus (rVac-H5 HA virus) was constructed. The immunogenicity of the expressed HA protein was characterized using goat antiserum, mouse monoclonal antibody, and human sera. The expressed HA protein localized both in the cytoplasm and on the cytoplasmic membrane of the thymidine kinase negative cells infected with the rVac-H5 HA virus, as determined by immunofluorescence assay. Western blot analysis demonstrated that the rVac-H5 HA protein was post-translationally processed by proteolytic cleavage of the HA0 precursor into HA1 and HA2 domains; and all of these HA forms were immunogenic in BALB/c mice. The molecular weight (MW) of each HA domain was the same as the wild-type H5 HA produced in Madin-Darby canine kidney cells infected with the H5N1 virus, but was higher than that expressed by a baculovirus-insect cell system. Sera from all H5N1 survivors reacted to HA0, HA1, and HA2 domains; whereas sera from H5N1-uninfected subjects reacted to the HA2 domain only, but not to HA0 or HA1, indicating that some cross-subtypic immunity exists in the general population. There was a lot-to-lot variation of the recombinant HA produced in the baculovirus-insect cell system that might affect the detection rate of antibody directed against certain HA domains.

Decreased expression of surfactant protein D mRNA in human lungs in fatal cases of H5N1 avian influenza.

Microarray analysis of gene expression profile of lungs from two fatal H5N1 influenza cases identified 3,435 genes with higher than twofold changes in mRNA levels as compared to those of normal lung. One thousand nineteen genes and 2,416 genes were up-regulated and down-regulated commonly, respectively. Gene ontology analysis identified several ontology terms with significant association with these genes, most of which are related to cellular metabolism and regulation of cellular process including apoptosis and chemotaxis. Pulmonary surfactant protein D (SP-D) was found to be down-regulated. Quantitative RT-PCR confirmed the levels of SP-D mRNA in the lungs infected with H5N1 to be lower than those of normal lungs and lungs from patients with acute respiratory distress syndrome. SP-D plays multiple roles in respiratory innate defense against various pathogens, regulation of inflammatory responses, and maintenance of alveolar integrity. Reduction of SP-D in H5N1 influenza may play important roles in the pathogenesis of the disease.

Reduction of seasonal influenza transmission among healthcare workers in an intensive care unit: a 4-year intervention study in Thailand.

OBJECTIVE: To evaluate the feasibility and effectiveness of an influenza control bundle to minimize healthcare-associated seasonal influenza transmission among healthcare workers (HCWs) in an intensive care unit (ICU) equipped with central air conditioning. METHODS: A quasi-experimental study was conducted in a 500-bed tertiary care center in Thailand from July 1, 2005, through June 30,2009. The medical ICU (MICU) implemented an influenza control bundle including healthcare worker (HCW) education, influenza screening of adult community-acquired pneumonia patients, antiviral treatment of patients and ill HCWs who tested positive for influenza, promotion of influenza vaccination among HCWs, and reinforcement of standard infection control policies. The surgical ICU (SICU) and coronary care unit (CCU) received no intervention. RESULTS: The numbers of influenza infections among HCWs during the pre- and postintervention periods were 18 cases in 5,294 HCW days and 0 cases in 5,336 HCW-days in the MICU (3.4 vs 0 cases per 1,000 HCW-days; P ! .001), 19 cases in 4,318 HCW-days and 20 cases in 4,348 HCW-days in the SICU (4.4 vs 4.6 cases per 1,000 HCW-days; Pp.80), and 18 cases in 5,000 HCW-days and 18 cases in 5,143 HCW-days in the CCU (3.6 vs 3.5 cases per 1,000 HCW-days; Pp.92), respectively. Outbreak-related influenza occurred in 7 MICUHCWs, 6 SICU HCWs, and 4 CCU HCWs before intervention and 0 MICU HCWs, 9 SICU HCWs, and 8 CCU HCWs after intervention.Before and after intervention, 25 (71%) and 35 (100%) of 35 MICU HCWs were vaccinated, respectively (P ! .001); HCW vaccination coverage did not change significantly in the SICU (21 [70%] of 30 vs 24 [80%] of 30; Pp.89) and CCU (19 [68%] of 28 vs 21 [75%]of 28; Pp.83). The estimated costs of US $6,471 per unit for postintervention outbreak investigations exceeded the intervention costs of US $4,969. CONCLUSION: A sustained influenza intervention bundle was associated with clinical and economic benefits to a Thai hospital.

The Practice of Electroconvulsive Therapy in Asia: Variations and Deviations From the Guidelines-A Response to Dr Grunhaus.

Electroconvulsive therapy (ECT) is widely used in most countries in Asia. There are several regards in which the practice of ECT in this region deviate from the guidelines issued by the American Psychiatric Association and the Royal College of Psychiatrists. The deviations are a matter of concern but are not surprising, considering that most previous surveys have also documented deviations from these guidelines. We are trying to explain all probable causes of this suboptimal practice, and then, we recommend how to improve the practice of ECT in Asian countries.

A survey of the practice of electroconvulsive therapy in Asia.

OBJECTIVE: To describe a comprehensive survey of the practice of electroconvulsive therapy (ECT) in Asia. METHOD: Between 2001 and 2003, a 29-item questionnaire was sent to 977 psychiatric facilities in 45 Asian countries. RESULTS: Completed questionnaires were returned by 334 (34.2%) institutions in 29 (64.4%) countries. Electroconvulsive therapy was available in 257 institutions in 23 countries. During the year before the survey, 39,875 patients (62% men) received a mean of 7.1 ECT treatments. Most patients (73.1%) were 18 to 44 years old; few were younger than 18 years (6.0%) or older than 64 years (4.4%). Indications for ECT were schizophrenia (41.8%), major depression (32.4%), mania (14.0%), catatonia (6.9%), drug abuse (1.8%), dysthymia (1.6%), and others. Brief-pulse ECT devices were used in only 115 (58.4%) of 197 institutions. Routine electroencephalographic monitoring was conducted in only 59 (23.0%) institutions. Bilateral electrode placement was invariable in 202 (78.6%) institutions. Unmodified ECT was administered to 22,194 (55.7%) patients at 141 (54.9%) institutions in 14 countries. Continuation ECT was available in only 115 (44.7%) institutions in 17 countries. No institution had a formal ECT training program. CONCLUSIONS: The practice of ECT in Asia may seem suboptimal: schizophrenia, not depression, is the most common indication; most institutions offer sine-wave ECT; unmodified ECT is commonly administered; bilateral electrode placement is invariable in most institutions; electroencephalographic monitoring is uncommon; continuation ECT is infrequent; and no formal training in ECT is available. We speculate that the suboptimal practices reflect felt needs and ground realities in standards of medical care in developing countries rather than a misuse of ECT.

Kinetics and longevity of antibody response to influenza A H5N1 virus infection in humans.

Anti-H5N1 antibody was determined by microneutralization, hemagglutination inhibition, and Western blotting assays in serial blood samples collected from eight Thai patients, including four fatal cases and four survivors. The antibody was detected as early as 5 days and, typically, with an increase in titer in paired blood at about 15 days after disease onset. The anti-H5 antibody response was long-lasting, for almost 5 years in cases which can be followed that far. In addition, cross-neutralizing activity to related clade 1 viruses was observed.