key: cord-0840202-rn2i3s5u authors: Palka-Kotlowska, M; Custodio-Cabello, S; Oliveros-Acebes, E; Khosravi-Shahi, P; Cabezón-Gutierrez, L title: Review of risk of covid-19 in cancer patients and their cohabitants date: 2021-02-05 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.01.072 sha: d20c436bdb2c922a92c7b56aa9f1cb7dc1c3687a doc_id: 840202 cord_uid: rn2i3s5u Background Patients with history of active malignancy are at increased risk of infection and COVID-19 related complications. Sanitary protection measures are not specifically recommended within household. We wanted to study the risk of seroconversion in cancer patients according to their household exposure. Patients and methods The seroprevalence study is a prevalence study in Torrejon de Ardoz (Spain), and analyzed the seeroprevalence of IgM and IgG antibodies in 104,299 volunteers (participation rate of 74.8% of population) from May 29th to June 5th, 2020. Personal authorization was requested to collect by questionnaire the test result from cancer patients who attended the outpatients department of the University Hospital of Torrejón and their cohabitants between June 1 st and June 19th 2020. Results 229 cancer patients were included in the study. Sixty-four of the 229 individuals tested positive for SARS-CoV-2 IgG antibodies (27.9%) and 22 patients were positive for SARS-CoV-2 IgM antibodies (9.6%). The overall seroprevalence (IgG or IgM positive) was 31.4% (general population seroprevalence was of 10% in Spain). Of 72 seropositive patients, 54.2% had intrafamilial exposure vs 45.8% did not. Among seronegative patients, 30.6% had seropositive cohabitants. The probability of seropositivity for a cancer patient was significantly related to intrafamilial exposure (OR of 2.684, 95% CI 1.51 – 4.76, p = 0.001). Conclusions Cancer patients are a high-risk group for SARS-CoV-2 infection, and could need to implement recommendations against virus transmission even in a household scenario as it is the main factor significantly related to seroconversion. The secondary attack rate of SARS-CoV-2 in household is 16.3%. Age of household contacts and spousal relationship to the index case are risk factors for transmission of SARS-CoV-2 within a household. Quarantine of index patients at home since onset of symptoms is useful to prevent the transmission of SARS-CoV-2 within a household ). In the case of non-household close contacts, sharing a vehicle, verbal interaction and contact with more than one index case were risk factors independently associated with SARS-CoV-2 transmission. We reviewed the serology results of 229 cancer patients and their cohabitants of the population based seroprevalence study in the city of Torrejon de Ardoz. The study J o u r n a l P r e -p r o o f included cancer patients who had symptomatic COVID 19 disease and those who were asymptomatic. Symptom based PCR misses a lot of SARS-CoV -2 asymptomatic cases. Close contact tracing reveals as one of the back bones of the control of transmission of SARS-CoV-2 as this is the only way to the identification of asymptomatic cases. The available findings, including those from our study, support physical distancing and minimising verbal interactions as part of community measures for prevention of SARS-CoV-2 transmission among close contacts. Testing of close contacts regardless of symptoms will reduce missed diagnoses, and it is very important in the cases of high risk patients as cancer patients. Household contacts, who are at high risk of SARS-CoV-2 transmission, should be prioritised for routine testing. Detection of SARS-CoV-2-positive household contacts would prompt either relocation of the person out of the household or implementation of physical distancing and other infection prevention measures within the household. The ongoing coronavirus disease in the 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has affected almost all countries worldwide. COVID-19 was first reported in Wuhan, China, in December 2019, among a group of individuals presenting with atypical pneumonia of unknown etiology (Lu H et al., 2020) . To date, January the 24 th 2021, there are over 97,264,519 reported cases and 2,107,554 deaths due to COVID-19 (World Health Organization, 2020). Individuals over 70 years old and patients with chronic conditions such as diabetes, hypertension or cardiopulmonary disease are at higher risk of severe disease J o u r n a l P r e -p r o o f complications and death (Wu et al., 2020) . However, the spectrum of disease severity and mortality from COVID-19 and the risk factors related to SARS-CoV-2 are unknown because of limitations of routine case detection and surveillance systems. Specifically, if the risk of SARS-CoV-2 infection is higher than the treatment benefit, it should be delayed until the risk-benefit balance is beneficial. Therefore, it is very important to be aware of the regional prevalence of COVID-19 (Sociedad Española de Oncología Médica, 2020). In studies of contact tracing in the cities of Shenzhen and Guangzhou, (China), the secondary attack rates were 14.9% and 10.2%, respectively among household contacts. In a study of the close contacts of ten US patients with COVID-19, the estimated household secondary attack rate was 10.5% (Bi Q et al., 2020, Burke RM et al., 2020). However, this was general population studies and not cancer patients population; the sample size was small for reliable interpretation and only symptom onset of primary cases was examined. Since the start of the alert by COVID-19 and until June 21st, 2020 (health alert end), were diagnosed, with a total cumulative incidence of 455 cases per 100,000 habitants in December 2020 and a maximum incidence of 835 per 100.000 habitants in May 2020. In this study, we wanted to investigate the risk of seropositivity in cancer patients according to their household exposure. We traced the patients who had positive serology and the serological results of their cohabitants. The main hypothesis is that there is a high risk of virus transmission at home because patients do not use preventive measures, and oncologic patients frequently need to go to the hospital to receive their treatments, so they are more exposed than general population to SARS-CoV-2 infection. The seroprevalence study ENE-Covid19 monitored cohort of close contacts provided a unique opportunity to study attack rates based on serological surveys in symptomatic or asymptomatic patients. We present the results of the prevalence of IgG and IgM antibodies against SARS-CoV- The SARS-CoV-2 seroprevalence study is a cross sectional study of Torrejón de Ardoz, (Madrid, Spain) carried out by the council of Torrejon de Ardoz (Ayuntamiento de Torrejon, 2020). It included all citizens over 1 year of age who would be interested in make the serological test. From a total of 139,452 registered citizens, 104,299 volunteers participated (74.8% of the population). The study was made between May 29th and June 5th, 2020, after approval of the institutional ethics board at Elche-Vinalopó and Torrevieja Hospital (Comunidad de Valencia, Spain). Individuals with positive IgM were directed to SARS-CoV-2 nucleic acid by real-time RT-PCR, regardless they were symptomatic or not. All individuals diagnosed with COVID-19 were admitted to hospital if had moderate or severe sympthoms and isolated until they were discharged, following at least two consecutive negative PCR tests on respiratory specimens collected 24 h apart. Using this information, we performed a retrospective cohort study in our center to evaluate the rate of seropositivity among cancer patients in our institution, and its relation to seropositive cohabitants. Authorization was requested to collect the serological test result from cancer patients who attended the outpatients department of the University Hospital of Torrejón and their cohabitants between 1st June and 19 th June 2020. Asymptomatic individuals were defined as those who reported no symptoms at all. Household contacts were defined as those who shared the same home as the index case, regardless of duration of contact. We classified the cancer patients according to if they were seropositive or not, the kind of treatment they were receiving and if they had seropositive household contacts or not. A total of 229 patients were included. All participants gave written informed consent before their participation in the study. Laboratory analysis of anti-SARS-CoV-2 IgG and IgM antibodies was assessed using a commercially available rapid test (Testsealabs® IgG/IgM Rapid Test Cassette, Hangzhou Testsea Biotechnology Co., Ltd) targeting the S1 domain of the spike protein of SARS-CoV-2. The serological test has the following characteristics: sensitivity (IgM 88%; IgG: 96%), specificity (IgM 100%; IgG 100%) and accuracy (IgM 94%; IgG 98%). The test is based on reliability studies carried out in various hospitals of the Spanish National Health System, and has the approval of the European Community and the ISO13485 certificate. The following studies were carried out to validate the test as an instrument for measuring health: a validation study of the selected test, before carrying out the study in a sample of randomly selected health workers. Comparing the results with the ELISA technique, with the aim of obtaining a gross agreement of over 80% for both measure. A concordance study performed on a randomly selected sample, which is performed (in addition to the serological test) for the detection of antibodies using ELISA techniques, with the aim of obtaining a kappa index > 0.7. A concordance study conducted with patients diagnosed at the Torrejón Hospital by PCR before the start of the study and who have attended serological tests (the required objective was to obtain a crude concordance greater than 95%). The validation study showed a diagnostic agreement of 93.6% between Testsealabas® and ELISA test. Intrafamilial exposure was defined as having one or more cohabitants in the same household with IgM or IgG antibodies against SARS-CoV-2. A patient or a cohabitant was considered seropositive when presented with antibodies IgM or IgG against SARS-CoV-2. Otherwise they were considered seronegative. We carried out a study where we analyzed the clinical characteristics of this cohort, which is published elswere (Cabezón-Gutierrez L, 2020) and the results of the Council population study were published on June 17 th 2020 (Ayuntamiento de Torrejon, 2020) Statistical calculations were performed using SPSS version 26. A comparison between categorical variables was computed using Fisher`s exact test or Pearson Chi-square test. A p-value of less than 0.05 was considered statistically significant. The following predictors were evaluated for inclusion in a final multivariable model using invariable binary logistic regression analysis: age group (<50.51-70,>70), sex (female and male), cancer type (respiratory, digestive, breast, urinary and male genital organs, female genital organs, and others), and cancer treatment (yes/no). A relaxed level significance (p<0.6) was used to identify variables. Goodness of fit of the model was evaluated by the Hosmer Lemeshow test. To estimate the degree of the association, odds ratios and respective 95% confidence intervals were calculated. General characteristics of our study population were as follows: proportion of men and women was well balanced and the mean age was 64 years Neither was it cancer stage. It is of note that neither active treatment nor absence of it during COVID-19 pandemic was significant for seropositivity. The rates of seropositivity are presented in Table 2 . Of 72 seropositive patients, 54.2% had intrafamilial exposure (cohabitants who were seropositive for SARS-CoV-2 IgM or IgG antibodies) vs 45.8% who did not. Among seronegative patients, 30.6% had cohabitants who had antibodies against SARS-CoV-2. The probability of seropositivity for a cancer patient was significantly related to intrafamilial exposure (OR of 2.684, 95% CI 1.51 -4.76, p= 0.001). Sixteen out of 72 seropositive patients (22%) were receiving chemotherapy, and 7 (43%) of them had familial exposure. The multivariable analysis confirmed that having seropositive cohabitants was the only risk factor for cancer patients to be seropositive themselves. (Odds Ratio 2.69, 95% CI 1.47 -4.9, p=0.01). (Figure 1 ). The high seropositivity rate among cancer patients detected in our study (overall seropositivity for IgG or IgM of 31.4%) and the risk factor of having seropositive cohabitants indicate that this population is more exposed to the virus infection than general population (seroprevalence of 5% in Spain and 11.3 in Madrid) (Pollán M et al., 2020) . When individually asked for data collection, cancer patients are a social cohort that has strictly followed the prevention recommendations against COVID-19 spread such as social distance of at least 1.5 m, frequent hand washing and the use of protective masks which were recommended in Spain during the first wave of COVD-19 outbreak. They also reported that in their homes the recommendations were not followed, and this is one of the weakness of the protection. Hence, we can suspect that cancer patients could be In Spain, first wave strict lockdown lasted 99 days. If a case of SARS-CoV-2 infection was detected, 14 days inhouse isolation was strongly recommended. If this isolation could J o u r n a l P r e -p r o o f be made in a different house it was optimal, but most patients did not have this possibility so isolation was done in the same house as their close relatives. Liu et al carried out a study of seroconversion in cancer patients and suggested a lower capacity for seroconversion in this group of patients (Liu T et al., 2020) . The main explanation was that it is an immunosuppressed population. In our study, 31.4% of patients did present seroconversion, which is a much higher prevalence than the one showed in the nationwide seroprevalence study ENE-COVID (Pollán M et al., 2020 Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission (Ng OT et al., 2020) . Eighty-seven patients out of 229 had seropositive cohabitants, and only 72 (31.4%) presented antibodies against SARS-CoV-2. We assume that they were exposed to the virus in some point of the lockdown (serological tests at Torrejon de Ardoz were done between May 29th and June 5th, 2020, and the lockdown lasted since 15 th March until 21st June 2020). This data suggest that close household contact may be the main risk factor for virus transmission, with a 54.2% risk of SARS-CoV-2 seropositivity if intrafamilial exposure existed (OR of 2.684, 95% CI 1.51 -4.76, p= 0.001). The main limitations of our study are the number of patients included and limited to outpatients, which can lead to selection bias since only those patients who felt good enough could undergo the serology analysis and come to oncology consultation. We did not made a design with a control group based on the study of Torrejon Council because we could not contact people who underwent the serology tests but were not our patients as dictates the law on personal data protection. In conclusion, cancer patients are a high-risk group for SARS-CoV-2 infection, and could need to implement recommendations against virus transmission even in a household scenario. 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