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Our take —

This study, available as a preprint and thus not yet peer reviewed, confirms that cats are highly susceptible to SARS-CoV-2 infection, and that dogs are less susceptible than cats, with limited viral shedding, and that both animals develop antibodies to the virus following infection which provide protection against re-infection in cats. More research will be needed to confirm if cats can transmit the virus back to humans or to other animals.

Study design

Prospective cohort; Ecological

Study population and setting

The study population included seven adult cats (1 male, 6 female, 5-8 years old) and three adult dogs (all female, 5-6 years old). Cats and dogs were housed in groups. Weight, body temperature, clinical status, and oral swabs were obtained prior to viral exposure, and all cats tested negative for feline enteric coronavirus antibody prior to starting the study. Cats were inoculated with 3×10^5 plaque forming units of SARS-CoV-2 and dogs received 1.4×10^5 plaque forming units intranasally. Three inoculated cats (cohort 1) were monitored for viral shedding via orapharyngeal swabs, nasal flushes, and blood samples between for 14 days post-inoculation. At 28 days post-inoculation, cats were re-challenged with 3×10^5 plaque forming units of virus, then oronasal samples were taken between for 14 days post re-challenge (up to 42 days after initial infection). Cats were euthanized at day 42 and tissues were collected for histopathology. Two cats (cohort 2) were exposed to the virus like cohort 1, then two naïve cats were introduced into the room with the infected cats 48 hours following initial infection. Inoculated cats were euthanized at day 5 post-inoculation, and tissues were collected for virus isolation and histopathology. Contact cats were euthanized at day 30 post-inoculation and necropsied. Dogs were sampled at the same frequency as cat cohort 1 for 42 days post-inoculation, but were not re-challenged with the virus.

Summary of Main Findings

None of the cats or dogs showed any clinical signs of infection, including fever or changes in body weight; the clearest pathological sign observed in cats was moderate rhinitis and minor interstitial pneumonia. All three cats in cohort 1 shed virus orally and nasally for up to five days post-inoculation. Contact cats from cohort 2 shed virus orally as early as 24 hours post-exposure. Cats in both cohort 1 and direct contact cats from cohort 2 developed antibodies to SARS-CoV-2 as early as 7 days post-inoculation that remained high until the end of the study. Re-challenged cats showed no signs of viral shedding during the 7 days following re-exposure, but did show a moderate increase in antibody titer. Viral shedding was not detected in any of the dogs post-infection, but dogs developed antibodies by day 14 post-exposure, although with lower titers than cats.

Study Strengths

Compared to previous experimental studies of SARS-CoV-2 infection in cats, this study examines shedding kinetics over time, assesses virus neutralization, seroconversion, and transmission in the same experiment. This is also the first study to report protective immunity against SARS-CoV-2 following repeated exposure.

Limitations

All animals were adults, so it is unclear whether the lack of observed clinical signs of infection changes with animal health status, age, and comorbidities. The study also does not investigate the potential for inter-species transmission, such as between cats and dogs, or between cats and humans.

Value added

The study confirms that cats are highly susceptible to SARS-CoV-2 infection in experimental conditions, and that they develop neutralizing antibodies that protect against subsequent challenge with the virus.

Our take —

This study showed high mortality among cancer patients with COVID-19 in the UK. Mortality was associated with known risk factors for COVID-19 mortality, including older age and comorbidities. There was no evidence of a positive association between non- palliative chemotherapy or other anticancer treatment and mortality due to COVID-19. COVID-19 prevention efforts among cancer patients should continue to be prioritized given the high mortality overall. This study suggests that oncologists should not withhold cancer treatment due to fear of increasing COVID-19 mortality. Larger multi-country prospective cohorts of cancer patients are needed to further evaluate this question, and to evaluate potential heterogeneity in outcomes across different cancer types, treatments and populations.

Study design

Prospective Cohort

Study population and setting

The primary objective of the study was to evaluate whether there were any differences in all-cause mortality, or hospital discharge, among COVID-19 patients with cancer who are on anticancer treatment (cytotoxic chemotherapy or other therapies) compared to cancer patients who are not on cancer treatment. This study analyzed data of all patients with active cancer diagnosed with COVID-19 using RT-PCR in 55 centers in the UK between March 18 and April 26, 2020. These centers were part of the UK Coronavirus Cancer Monitoring Project (UKCCMP), a national initiative established in March 2020 to prospectively collect relevant data on COVID-19 patients with cancer.

Patient-level data were collected on relevant demographic and clinical information, including age and presence of comorbidities, cancer type (localized vs. metastatic) and stage, and cancer treatment history, specifically history of chemotherapy, immunotherapy, hormonal therapies, or radiotherapy within 4 weeks SARS-CoV-2 infection.

Summary of Main Findings

Overall 800 symptomatic and laboratory-confirmed COVID-19 patients were enrolled. The most common cancer types involved digestive organs (19%), hematological (14%), and breast (13%). Of these, 43% had metastatic cancer, while 19% had primary localized tumors. The vast majority (79%) of participants had other comorbidities apart from cancer including cardiovascular disease, hypertension, and diabetes. Half (52%) had mild COVID-19 disease, 39% required oxygen and 7% were admitted to an intensive therapy unit (ITU).

Overall, 28% (226) of the patients died, and 93% of those deaths were attributed to COVID-19. Mortality among patients in ITU was around 43%. Factors positively associated with mortality were older age (adjusted OR) aOR: 9.42 (6.56–10.02), having at least one comorbidity including cardiovascular disease 2.32 (1.47–3.64) or hypertension 1.95 (1.36–2.80), being male and having severe COVID-19 disease. There was no apparent difference in mortality comparing cancer patients on any anticancer treatment in the 4 weeks prior to COVID-19 infection versus cancer patients not on treatment.

Study Strengths

The study is a multi-center nationwide prospective cohort of cancer patients with laboratory-confirmed COVID-19 in the UK. The data collection process was rigorous, in real time and included important clinical and demographic variables that were adjusted for in the analyses.

Limitations

There is potential of selection bias. Symptomatic individuals requiring medical attention may be overrepresented which may in part explain the high overall mortality. The true burden of SARS-COV2 among cancer patients can also not be estimated with these data. Furthermore, the number of patients on non-chemotherapy cancer therapies was small, warranting caution when interpreting findings of these smaller groups.

Value added

Before this study, there was mixed evidence from small studies on the association of cancer treatment and COVID-19 morbidity and mortality. This is the largest prospective cohort study to date evaluating whether chemotherapy or other anticancer treatment are associated with higher mortality among cancer patients with COVID-19. The findings provide valuable data that can inform clinical decision making for cancer patients in the near future.

Our take —

This study, available as a preprint and thus not yet peer reviewed, found that, of 13,278 healthcare workers from two hospital settings in Paris, 1,344 (10%) were symptomatic with potential COVID-19. Following testing, 373 (28%) tested positive for SARS-CoV-2 infection from February 24 to April 10, 2020, for an overall attack rate of 2.8% among healthcare workers. PPE use increased over the course of the study, and just over 60% (n=209/336, 62%) of infected healthcare workers reported using PPE always or almost always in the hospital. This study is likely affected by selection bias resulting in an underestimation of infection, given that only symptomatic workers were tested and provided additional information.

Study design

Prospective Cohort

Study population and setting

The objective of this study was to describe the disease dynamics and risk factors for SARS-CoV-2 infection among healthcare workers. Among 13,278 healthcare workers in two tertiary-care university hospitals in central Paris, including child and adult healthcare settings, 1,344 symptomatic healthcare workers were tested for SARS-CoV-2 from February 24 to April 10, 2020. Of these, 373 tested positive, and 336 (90%) responded to the phone interview to collect demographic and exposure information.

Summary of Main Findings

Among the 13,278 total healthcare workers, 1,344 were symptomatic (10%) and 373 (28%) of symptomatic workers tested positive. The overall estimated attack rate was 2.8%: in the adult setting, 251 (3.2%) of 7,916 healthcare workers tested positive with symptoms, and in the pediatric setting, 122 (2.3%) out of 5,362 tested positive with symptoms. The epidemic curve peaked on March 31, 2020, and then declined until the end of the study. Most positive and symptomatic workers were women (265, 79%), had patient-facing roles (234, 70%), and were not in COVID-19-specific wards (261, 78%). Over half of healthcare workers also reported wearing a mask always/most of the time at the hospital (141, 63% in adult setting, 68, 64% in children setting), and having >4 close contacts with colleagues per day without a mask (118, 52% in adult setting, 63, 59% in children setting). Outside of the hospital, the majority reported using public transportation (134, 59% in adult setting, 67, 62% in children setting), but the minority reported having a child in school or nursery outside the home, or wearing a mask outside the house. Over the course of the study, healthcare workers’ reported PPE use increased and leveled off, while close contact with a COVID-19 patient without PPE remained relatively stable

Study Strengths

This study had a large sample size of health workers, with data on their PPE practices and out-of-hospital exposure collected, which allows the study to assess trends over time, which were presented graphically. This out-of-hospital exposure data also included information on potential exposure from their children. Data is disaggregated by adult versus pediatric healthcare settings.

Limitations

The study is limited by only testing symptomatic healthcare workers, thus underestimating positive cases because asymptomatic workers were not tested. They also did not assess potential exposure among non-cases, so they could not make comparisons whether certain exposure routes were more likely to lead to infection than others.

Value added

This is one of the largest studies of healthcare workers to date that includes information on potential exposure routes over a number of daily domains including mask-wearing, contact with other colleagues, use of public transport, and children in school/nursery.

Our take —

In a large study of over 2 million community members and health care workers, available as a preprint and thus not yet peer reviewed, healthcare workers were found to have more than a 3-fold increase in risk of a reported positive SARS-CoV-2 test, even after adjustment for having received a test. Among healthcare workers, those with inadequate personal protective equipment had higher risk. Access to adequate personal protective equipment did not completely eliminate risk for those caring for COVID-19 patients.

Study design

Prospective Cohort

Study population and setting

Community members and frontline healthcare workers who were prospectively recruited via social media and direct invitations through existing cohort studies, were followed longitudinally and reported on whether they received a positive SARS-CoV-2 test. Data was reported through the COVID Symptom Study smartphone application and were collected between March 24 and April 23, 2020 from the United Kingdom and the United States. Data on demographic information, comorbidities, symptoms, and SARS-CoV-2 testing were captured through the app by self-report. For healthcare workers, defined as those with direct patient contact, additional information was collected about patient interactions and access to personal protective equipment. Cox proportional hazards were used to model adjusted hazard ratios of a positive SARS-CoV-2 test. Secondary analyses were conducted to account for likelihood of receiving a test. Subgroup analyses among healthcare workers also examined factors related to PPE availability.

Summary of Main Findings

A total of 2,810,103 individuals were enrolled– 670,298 individuals were excluded who had follow-up time less than 24 hours, and 4615 who previously tested positive at enrollment. Among the remaining 99,795 frontline healthcare workers and 2,035,395 community members, a total of 34,435,272 person-days were included; 5545 incident reports of a positive SARS-CoV-2 test were reported. Incidence was 48.2 per 100 person-years among healthcare workers and 4.01 per 100 person-years among the general community. Healthcare workers had an adjusted hazard ratio of 11.6 (95% CI 10.9-12.3) for reporting a positive test compared with the general community population. Using methods to adjust for the likelihood of receiving a test, healthcare workers remained at significantly greater risk of a positive test (aHR=3.40, 95% CI 3.37-3.43). In the subgroup analyses looking among healthcare workers, those with adequate personal protective equipment (PPE) had lower risk than those reporting reuse of, or inadequate PPE.

Study Strengths

The use of the novel mobile application to collect data allowed for the prospective collection of data on over two million community individuals and close to 100,000 healthcare workers. The study utilized two different approaches to account for higher likelihood of testing among healthcare workers, and the significantly higher risk among healthcare workers were robust to these adjustments.

Limitations

Recruitment for this study was not random, and may not capture certain underrepresented groups, including older adults. There is also the potential for emigrative selection bias in this study. A large proportion of those originally enrolled did not have any follow-up time greater than 24 hours. Participants were followed until they reported a positive test or the time of last data entry. This assumes that those who stopped providing data were represented by those who continued to provide data; incidence may be overestimated if those less likely to test positive were less likely to engage in follow-up.

Value added

This study directly compares frontline healthcare workers and community individuals to understand differences in risk and the role of personal protective equipment.

Our take —

In this large, prospective cohort study that began during the early stages of the COVID-19 outbreak, the clinical presentation and outcomes of 20,133 patients hospitalized in the UK with COVID-19 were described. Possibly due to the high median age (80 years), the mortality rate in the study was higher than previous reports of ICU patients in Italy and the US, but common symptoms, comorbidities, and factors associated with mortality were similar.

Study design

Prospective Cohort

Study population and setting

This prospective cohort study includes 20,133 patients with COVID-19 who were admitted to 203 acute care hospitals in England, Scotland, and Wales between February 6 and April 19, 2020 with follow-up through May 3, 2020. The study population accounts for 34% of all COVID-19 hospital admissions for the included countries.

Summary of Main Findings

Participants had a median age of 73, 60% were male, 1.5% were <18 years old, and 100 were pregnant. Most patients reported respiratory symptoms (cough, fever, and shortness of breath), though some patients also experienced clusters of musculoskeletal and enteric symptoms; only 4.5% of patients were asymptomatic. The majority of patients had at least one comorbidity (77.5%), and the most common comorbidities were cardiac disease (31%), diabetes with/without complications (28%), chronic pulmonary disease (18%), and chronic kidney disease (16%). Over half of patients (55%) received high flow oxygen during hospitalization, and 17% required admission to high dependency or intensive care units. Forty one percent of patients were discharged alive, 26% died, and 34% were still hospitalized at the time of analysis. Factors independently associated with mortality in multivariable Cox proportional hazards analysis included: increasing age, male sex, chronic cardiac disease, chronic pulmonary disease, diabetes, obesity, chronic neurological disorder, dementia, malignancy, and moderate/severe liver disease. The median time from onset of symptoms to hospital presentation was 4 days (interquartile range 1-8).

Study Strengths

This was a very large multi-site study, encompassing more than a third of all hospitalized COVID-19 patients in the study region. Data collection began during the early phase of the outbreak. Future studies plan to link to administrative healthcare databases to assess potential selection bias.

Limitations

Missing data, which seemed to be a pervasive problem, was not imputed. A large portion of patients were still hospitalized at the time of analysis, so the mortality rate is the minimum total mortality that will be observed. Because enrollment began in the early phases of the outbreak, COVID-19 screening and testing criteria changed throughout the study period, potentially resulting in the study population including sicker patients. Findings may not be generalizable to individuals with more moderate or mild disease progression.

Value added

This very large and rapidly conducted study describes the clinical characteristics and outcomes of 20,133 patients at 203 hospitals in the UK (England, Scotland, and Wales).

This article has been retracted due to concerns over data veracity.

Our take —

In this study of 326 patients with laboratory-confirmed SAR-CoV-2 infection in Shanghai, severe disease was more likely to be associated with host factors than with viral characteristics. Older age, reduced levels of CD4+ and CD8+ T cells, and elevated levels of inflammation, specifically Interleukin-6 and Interleukin-8, were all statistically associated with clinical progression in multivariate adjustment; whereas, viral lineage and specific mutations were not.

Study design

Prospective Cohort

Study population and setting

This study included 326 patients with laboratory-confirmed SARS-CoV-2 admitted to the Shanghai Public Health Clinical Center in Shanghai, China from January 20 to February 25, 2020. Data collection included clinical and epidemiological characteristics, and serum cytokine measurements were obtained from 228 of these patients. Viral genome sequences from 112 patients were generated and used to analyse changes in the virus over time. The investigators characterized associations between clinical, immunological, and genomic parameters and disease severity (asymptomatic, mild, severe, and critical).

Summary of Main Findings

The median age was 51 years, and 53% were male. Among all 326 patients, 38% had at least one comorbidity upon admission. A majority (n=293) presented with mild disease. Two distinct groups, or clades, of the virus were identified, with one lineage linked to the Wuhan seafood market; both, however, exhibited similar virulence and clinical manifestations. Phylogenetic analysis indicates that the earliest possible spillover to humans occurred in late November 2019, and that there was limited variation in the virus genome in the sequences collected. Decreased levels of CD3+, CD4+, and CD8+ T cells were significantly associated with disease severity. Levels of IL-6 and IL-8 6 to 10 days post-symptom onset were significantly higher in critical cases relative to non-critical cases. The primary factors associated with disease severity in univariate analyses were higher age, lymphocyte count upon admission, presence of comorbidity, and male sex. In multivariate analysis, higher age and reduced lymphocyte count remained significantly associated with disease severity.

Study Strengths

This study examined a broad array of inflammatory biomarkers, including eleven cytokines and several lymphocyte subsets, as well as the genomic sequences from a relatively large sample of confirmed COVID-19 cases, and linked these characteristics with clinical progression.

Limitations

Variable selection method for multivariate analyses is unclear. The timing of the measurements of inflammatory biomarkers relative to the onset of clinical symptoms is unclear. Methodology for determining sequencing variants is simplistic and unclear.

Value added

This is one of the first studies to examine a broad array of inflammatory biomarkers, including eleven cytokines and several lymphocyte subsets, in conjunction with genomic sequences from a relatively large sample of confirmed COVID-19 cases, and to link these characteristics with clinical progression and epidemiological factors. It also provides phylogenetic evidence that mutations in the viral genome are not linked to clinical progression, suggesting that clinical progression is more closely linked with host factors than viral characteristics.

Our take —

The results of this study add to a growing body of literature suggesting that elevated levels of proinflammatory cytokines, such as IL-6, and markers of thrombosis, such as D-dimer, influence severe clinical presentation and mortality due to COVID-19, although there is no data presented on levels prior to infection, which limits attributing the elevations to infection. Additionally, similar to other studies, patients with cardiac and pulmonary comorbidities were at increased risk of mortality. Research on the pathogenesis of inflammatory and coagulation processes of COVID-19 are important and ongoing.

Study design

Prospective Cohort

Study population and setting

This prospective cohort study includes 257 critically ill adults with laboratory-confirmed COVID-19, who were admitted to two New York-Presbyterian hospitals between March 2 and April 1, 2020. Critical illness was defined as having acute hypoxaemic respiratory failure requiring mechanical ventilation or high-level supplemental oxygen at or during hospitalization. Patients were followed until April 28, 2020 or discharge from hospital.

Summary of Main Findings

Among 1150 adults diagnosed with COVID-19 at the two hospitals, 257 were critically ill and included in the study. Among those, 101 (39%) died in the hospital (median duration in hospital: 9 days), 94 (37%) remained hospitalized (median duration of hospitalization: 33 days), 4 (2%) were transferred to a different hospital, and 58 (23%) were discharged alive. In adjusted analyses, older age, chronic cardiac disease (coronary artery disease or congestive heart failure), COPD or interstitial lung disease, elevated IL-6 levels, and elevated D-dimer levels were independently associated with in-hospital mortality.

Study Strengths

Data on demographics, medical history, comorbidities, vital signs, and biochemical parameters were collected prospectively on standardized case report forms, which were developed in collaboration with WHO and the International Severe Acute Respiratory and Emerging Infection Consortium. Participants were followed for at least 28 days. The authors provide well-described justification for the variables included in their multivariable model.

Limitations

Missing data were not imputed, so participants included in the multivariable model did not include the full study population, but the exact number is unclear. A large portion of participants remained hospitalized at the end of follow-up, and were (appropriately) censored, but their outcomes are unknown. The study population comprised patients from only 2 hospitals (both in New York City), which may limit generalizability. Data are limited to critically ill cases who have been hospitalized and findings may not be generalizable to less severe patients.

Value added

This is one of the largest prospective studies (to date) examining characteristics of critically ill COVID-19 patients in the United States.

Our take —

A study of dogs from households with COVID-19 cases in Hong Kong demonstrates that occasional human-to-dog transmission of SARS-CoV-2 can occur, producing infection with limited to no clinical symptoms, viral shedding in the nasal passages, and the development of antibodies following resolution of infection. While there is still no evidence that dogs can infect other dogs or humans, dogs in households with COVID-19 cases should be isolated to prevent infection.

Study design

Prospective cohort; Ecological

Study population and setting

The study focuses on fifteen dogs and seven cats from households with known COVID-19 cases that were quarantined and tested by the Hong Kong Agriculture, Fisheries, and Conservation Department in Hong Kong, China, as of March 27, 2020.

Summary of Main Findings

Two dogs out of the fifteen tested positive for SARS-CoV-2: a 17-year-old male Pomeranian with pre-existing diseases and a 2.5-year-old male German Shepherd in good health. The owner of the Pomeranian developed symptoms of COVID-19 on February 12, 2020 and was diagnosed on February 24, 2020; a female domestic helper developed fever on February 16, 2020. Five consecutive nasal swabs from the Pomeranian tested positive for SARS-CoV-2 genetic material between February 25 and March 9, 2020; all rectal and fecal samples tested negative. The owner of the German Shepherd developed symptoms on March 10, 2020 and was diagnosed with COVID-19 on March 17, 2020. Oral and nasal swabs from the dog tested positive for SARS-CoV-2 genetic material on March 18 and 19, 2020; rectal swabs from March 18, 2020 also tested positive, although with lower viral load than oral and nasal swabs. A second dog from the same household tested negative on five occasions between March 18 and 30, 2020. Both positive dogs showed no clinical signs of infection but produced measurable antibody titers, on March 3, 2020 for the Pomeranian and March 23,2020 for the German Shepherd. Sequencing of viral genetic material from both dogs showed that the viruses in both dogs were identical to those from their respective owners, but the viral clusters in the two households were distinct from one another.

Study Strengths

Compared to other studies focused on testing community dogs, the study focused only on dogs from COVID-19 patients to ascertain whether human-to-dog transmission can occur. The sequencing of the virus in the human cases and in the infected dogs was important for confirming human-to-dog transmission (rather than independent infection from a community source).

Limitations

With the very small sample size, it is difficult to determine the frequency of human-to-dog transmission of SARS-CoV-2, the possibility of dog-to-dog transmission, and the absence of clinical signs in infected dogs. The focus in this study on dogs from COVID-19 patients certainly overestimates the frequency of human-to-dog transmission relative to the larger population of dogs.

Value added

The evidence presented in this study demonstrating occasional human-to-dog transmission of SARS-CoV-2 confirms anecdotal reports of dogs becoming infected with SARS-CoV-2, and experimental transmission studies confirming that dogs are susceptible to SARS-CoV-2 infection, although to a lesser degree than cats.

Our take —

This study provides an important estimation of household secondary infection in Zhuhai, China; they found the secondary infection rate to be 32.4% (95% CI: 22.4 – 44.4%), with a serial interval of 5.1 days (95% CI: 4.3 – 6.2 days). Weaknesses included a somewhat limited sample size (35 households, 48 secondary cases among 148 exposed contacts), and the lack of a robust a priori determined statistical approach to estimate risk factors for transmission

Study design

Prospective Cohort

Study population and setting

The study objective was to estimate the risk of secondary transmission within households and the associated risk factors for secondary infection. From January to February 2020 in Zhuhai, China, the study identified 104 probable/confirmed COVID-19 cases in 46 households, and enrolled 35 people who met inclusion criteria: 1) a confirmed case, 2) the only index case in their household, and 3) lived with others in their household. All 35 index cases and their 148 contacts completed study questionnaires, and the 148 household contacts were then prospectively followed for 21 days for symptom monitoring, and naso-/oropharyngeal swabs were collected every 3 to 7 days during the study period to test for SARS-CoV-2 infection.

Summary of Main Findings

Among the 35 households, 22 (62.9%) had a secondary infection, with 48 secondary cases (of which 10.4%, n=5 were asymptomatic) among the 148 exposed contacts, with an estimated secondary infection rate of 32.4% (95% CI: 22.4 – 44.4%). Using a multivariate regression model, they found having an underlying medical condition increased the odds of susceptibility of infection by 5.99 times (95% CI: 1.81 – 19.83), direct exposure to Wuhan increased the odds of infection by 4.14 times (95% CI: 1.24 – 13.68), having no protective measures after the index case developed symptoms increased the odds by 4.95 (95% CI: 1.59 – 15.39), and sharing a vehicle with them increased it by 4.37 (95% CI: 1.80 – 10.58). Notably, whether the index case wore a mask, whether the index case self-isolated while indoors, and the number of hours spent at home with the index case were not associated with the odds of secondary infection. Using a log-normal model for household secondary cases, the estimated median incubation period was 4.3 days (95% CI: 3.4 – 5.3 days), and the serial interval between successive cases was estimated at 5.1 days (95% CI: 4.3 – 6.2 days).

Study Strengths

The study had prospective follow-up of households which allowed for estimation of the secondary infection rate and serial interval to better understand transmission, and to construct an epidemiological curve of the date of symptom onset, diagnosis, and hospital admission within the sample. Authors also collected a number of demographic and clinical variables among not only the household contacts, but the index cases (e.g. symptoms), and the household (e.g. ventilation/disinfection, number of contacts in the house, etc.). Using naso-/oropharyngeal swabs allowed them to confirm case status among the contacts, as opposed to relying on clinical diagnosis based on symptoms, which allowed for asymptomatic cases to also be included.

Limitations

To construct their major multivariate model, the study used different models for the index case, contact case, and household, and then based on these results, took the most significant variables to construct their final model. This is not a valid approach to integrate these multi-level variables, and likely leads to confounding, especially given that the final model was based on significance level and not a priori defined confounders reasonably thought to play a role. In addition, they had a relatively small sample size, which is reflected in wide confidence intervals, and may lead to an underpowered analysis. They also assumed that secondary infections were exposed via the index case only, which is an oversimplification of potential transmission routes and may overestimate secondary attack rates. There may also be selection bias in the households that were selected, and households with more cases may be more likely to seek medical care and evaluation, which could again overestimate the secondary infection rate.

Value added

The study has prospective follow-up of households in order to determine the secondary infection rate and serial interval and determined potential risk factors for secondary infection.