COVID-19 Negative Individuals Research Articles

Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection.

Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period. We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001. Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.

A cross-sectional study on the nasopharyngeal microbiota of individuals with SARS-CoV-2 infection across three COVID-19 waves in India.

Multiple variants of the SARS-CoV-2 virus have plagued the world through successive waves of infection over the past three years. Independent research groups across geographies have shown that the microbiome composition in COVID-19 positive patients (CP) differs from that of COVID-19 negative individuals (CN). However, these observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at the Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India and subjected to 16s rRNA gene amplicon - based sequencing. We found variations in the microbiota of symptomatic vs. asymptomatic COVID-19 patients. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. To our knowledge, this is the first analytical cross-sectional study of this scale, which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Although no clear signatures were observed, this study shall pave the way for a better understanding of the disease pathophysiology and help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.

Evaluating immunohaematological profile among COVID-19 active infection and recovered patients in Ghana.

IntroductionThe rapid spread of COVID-19 has been a global public health problem and it is yet to be put under control. Active COVID-19 is associated with unrestrained secretion of pro-inflammatory cytokines and imbalances in haematological profile including anaemia, leukocytosis and thrombocytopaenia. However, the haematological profile and immune status following recovery from COVID-19 has not been recognized. We evaluated the immunohaematological profile among COVID-19 patients with active infection, recovered cases and unexposed healthy individuals in the Ashanti region of Ghana.MethodologyA total of 95 adult participants, consisting of 35 positive, 30 recovered and 30 unexposed COVID-19 negative individuals confirmed by RT-PCR were recruited for the study. All the patients had the complete blood count performed using the haematological analyzer Sysmex XN-1500. Their plasma cytokine levels of interleukin (IL)-1β, IL-6, IL-10, IL-17, tumour necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) were analysed using ELISA. Statistical analyses were performed on R statistical software.ResultThe Patients with COVID-19 active infection had significantly higher levels of IL10 (181±6.14 pg/mL vs 155.00±14.32 pg/mL vs 158.80±11.70 pg/mL, p = 0.038), WBC count (5.5±0.4 x109 /L vs 4.5±0.6 x109 /L vs 3.8±0.5, p < 0.0001) and percentage basophil (1.8±0.1% vs 0.8±0.3% vs 0.7±0.2%, p = 0.0040) but significantly lower levels of IFN-γ (110.10±9.52 pg/mL vs 142.80±5.46 pg/mL vs 140.80±6.39 pg/mL, p = 0.021), haematocrit (24.1±3.7% vs 38.3± 3.0% vs 38.5±2.2%, p < 0.0001), haemoglobin concentration (9.4±0.1g/dl vs 12.5± 5.0g/dl vs 12.7±0.8, p < 0.0001) and MPV (9.8±0.2fL vs 11.1±0.5fL vs 11.6±0.3fL, p < 0.0001) compared to recovered and unexposed controls respectively. There were significant association between IL-1β & neutrophils (r = 0.42, p<0.05), IL-10 & WBC (r = 0.39, p<0.05), IL-10 & Basophils (r = -0.51, p<0.01), IL-17 & Neutrophil (r = 0.39, p<0.05) in the active COVID-19 cases.ConclusionCOVID-19 active infection is associated with increased IL-10 and WBC with a concomitant decrease in IFN-γ and haemoglobin concentration. However, recovery from the disease is associated with immune recovery with appareantly normal haematological profile.

Effectiveness of BBV152/Covaxin and AZD1222/Covishield vaccines against severe COVID-19 and B.1.617.2/Delta variant in India, 2021: a multi-centric hospital-based case-control study

ObjectivesIndia introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. MethodsWe did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. ResultsWe enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. ConclusionBBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Respiratory viral infections other than SARS CoV-2 among the North Indian patients presenting with acute respiratory illness during the first COVID-19 wave.

Acute respiratory infections due to viral or bacterial etiology can cause 60 deaths per one lakh population. Viral etiology is more common as compared to bacterial, but lack of definite diagnosis leads to increased usage of empirical antibiotics. During the first wave of the COVID-19 pandemic, there was a need to identify co-infections especially in severe acute respiratory illness (SARI) patients to identify it as one of the cofactors for increased severity of illness and to identify the causative agents in COVID-19 negative individuals. The SARS CoV-2 real time PCR was carried out using ICMR approved kits and the other respiratory viruses were detected using the multiplex commercially available real time kit. A total of 186 patients presenting with either SARI (89.8%) or influenza like illness (10.2%) were included in the study. Out of these, 43 (23.1%) were positive for SARS CoV-2 RNA and 2 (4.6%) patients with SARI showed concomitant infection with either human rhinovirus or human respiratory syncytial virus . Out of 143 patients negative for SARS CoV-2, 35 (24.5%) were positive for one or more microbial infections and 28 (19.6%) infected with other respiratory viral infection most common being human rhinovirus. The results suggest that viral coinfections are significantly higher among COVID-19 negative individuals (24.5% vs 4.6%) presenting with respiratory illness as compared to COVID-19 positive individuals possibly due to viral interference and competitive advantage of SARS-CoV-2 in modulating the host immunity. Further detailed research is required for the understanding of mechanisms of viral co-infection.

Interferon Gamma Release Assay Mitogen Responses in COVID-19

Background Elevated cytokine release and T cell exhaustion have been associated with COVID-19 disease severity. T cell activity may be indirectly measured through interferon gamma release assays (IGRAs), which use mitogen stimulation of T lymphocytes as a positive control. In our institution, an unexpectedly high rate of indeterminate IGRAs was noted in COVID-19–positive patients. We aimed to evaluate the clinical characteristics associated with indeterminate IGRA results and the difference in mitogen responses between COVID-19–positive and COVID-19–negative patients. Methods We reviewed all patients, regardless of COVID status, who were admitted between March 1, 2020, and May 31, 2020, and for whom an IGRA was collected. For COVID-19–positive individuals, we evaluated the statistical association of their IGRA results and clinical characteristics, including demographics, laboratory values, comorbidities, and hospitalization-related outcomes. For both COVID-19–positive and COVID-19–negative individuals, we evaluated IGRA mitogen control values relative to COVID-19 status as stratified by absolute lymphocyte count. Results In COVID-19–positive patients, indeterminate IGRA results were statistically associated with white blood cell count and other markers of inflammation. When comparing COVID-19–positive and COVID-19–negative patients, we noted a statistically significant difference in IGRA mitogen control values when stratified by absolute lymphocyte count. Conclusions Indeterminate IGRA results were associated with higher levels of inflammatory markers. Furthermore, when comparing mitogen responses between COVID-19–positive and COVID-19–negative patients, there was an observed difference in T cell reactivity between the groups. The mitogen response in IGRAs may serve as a surrogate for T cell function and a marker of disease severity in COVID-19.

Infekce SARS-CoV-2 a postižení slinivky břišní

SARS-CoV-2 is an etiological factor in several diseases that the WHO designated covid-19. Covid-19 infection may affect the digestive tract, including the pancreas. The main/most common symptoms of covid-19 include fever (71.6%), cough (68.9%) subjective feeling of shortness of breath (71.2%). The gastrointestinal symptoms include abdominal pain, nausea and vomiting and/or diarrhea. The relationship of covid-19 and pancreas affection is not clearly described. A common finding is hyperlipasemia, eventually hyperamylasemia. Both conditions are usually associated with either no or minimal histomorphological changes, i.e. changes referred to as edematous glandular infiltration. Rarely, a necrotic form was reported. Nevertheless, the mortality of patients with acute pancreatitis who were covid-19 positive was higher than in covid-19 negative individuals. The available data indicate there is a link between covid-19 infection and the pancreas presenting as an acute disorder of the gland. SARS-CoV-2 impairment of both exocrine and endocrine function of the pancreas is multifactorial. It is debatable whether the involvement of the gland is directly related to the presence of the virus or whether it is an epiphenomenon. Angiotensin-converting enzyme 2 (ACE-2) receptors, inflammatory changes (especially in pancreatic beta cells), together with high IL-18 levels, virus-induced lipotoxicity and immunological dysregulation play an important role in the induction of pancreatic damage. During the covid-19 pandemic, pancreatopathies represent a very lively topic and are being studied intensively. Keywords SARS-CoV-2, COVID-19, chronic pancreatitis, pancreas, endoscopy

Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection.

BackgroundAssessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection.MethodsThis is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants.FindingsA total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine.InterpretationOur study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants.Fun1dingNone.

Study of Hearing Status in COVID-19 Patients: A Multicentered Review.

To evaluate the hearing status of COVID-19 patients and compare with control group. Prospective study carried out in 9 institutes. The pure tone audiogram and impedance audiometry of COVID-19 patients performed initially and at 3 months follow up. The control group consisted COVID-19 negative individuals with no history of ear related diseases. The average of air and bone conduction threshold (AC and BC) were compared between the COVID-19 patients and control group using independent t-test with a p value of less than 0.05 considered significant. Total of 331 patients, age 32 ± 4.3 years, 66.7% males and 33.3% females were included in the study. There were 80 individuals in the control group. Aural symptoms were, tinnitus in 1.8%, aural fullness in 1.4%, hearing loss in 3. 9%, and ear ache in 1.8% were present initially, resolved at 3 months follow up. The impedance audiometry demonstrated type B and type C curve in 5.1% and 1.15% ears, and out of these 64.7% and 40% improved at 3 months follow up respectively. No significant difference observed between the average AC and BC of the COVID-19 patients and control group. The COVID-19 infection may present with aural symptoms; however, it was concluded that there was no significant difference in the hearing status of the COVID-19 positive patients in comparison to the control group. The presence of some changes in the normal functioning of the eustachian tube and middle ear in the COVID-19 infection was also highlighted.

Cross-Reactivity of SARS-CoV-2 Laboratory Diagnostics to Endemic Diseases in Africa: A Diagnostic Accuracy Study

Background: Serology is a great tool to assess the level of immunity against SARS-CoV-2 in settings with limited access to molecular diagnostics. However, African populations displays a particular immunological profile with massive circulation of infectious agents from different aetiologies that can affect assays performance.Methods: We evaluated the OMEGA Diagnostics COVID-19 ELISA-IgG and the ID Screen® SARS-CoV-2-N IgG Indirect in Senegal using a panel of 636 blood samples covering several African-endemic diseases and healthy donors to determine test sensitivity and specificity. The sensitivity panel of sera includes 461 serum samples collected from 91 patients hospitalized for COVID-19 disease. COVID-19 cases were confirmed by qRT-PCR and samples were collected on an interval of three days until viral clearance. In addition, 272 sera obtained from COVID-19 negative individuals were selected from a well-documented biobank of sera collected before the COVID-19 outbreak.Finding: High-cross reactivity have been found in individuals with a history of exposure to Chikungunya, HIV, malaria (Plasmodium falciparum), rheumatoid factor as well as healthy donors with respective specificities of 55%, 41.8%, 70%, 70% and 75%. ELISA experiments with commercial assays targeting either SARS-CoV-2 Nucleocapsid protein and Spike 2 protein or nucleocapsid protein only suggest that cross-reactivity might be directed against Spike 2 protein and not Nucleocapsid protein. Further samples characterisation reveals that anti-malaria IgG is the leading cause of such poor specificities, but exposure to other diseases contributed as well.Interpretation: We anticipate that COVID-19 seroprevalence can be biased if assays are not contextualized. Since malaria is endemic in African settings, we propose that a particular attention must be given in serological surveillance of COVID-19 or anti-SARS-CoV-2 antibodies quantification as vaccines are being rolled out.FundingUK Foreign, Commonwealth and Development Office/Wellcome Trust Joint Initiative for Research in Epidemic Preparedness and Response (JIREP grant number 220764/Z/20/Z).Funding Information: UK Foreign, Commonwealth and Development Office/Wellcome Trust Joint Initiative for Research in Epidemic Preparedness and Response (JIREP grant number 220764/Z/20/Z).Declaration of Interests: JRAF was an employee of Mologic Ltd, which was the development partner of one of the ELISAs adopted in this study. The remaining authors declare no competing interest.Ethics Approval Statement: Pre-COVID-19 samples for malaria (PCR), dengue, yellow fever, Zika, Chikungunya, Influenza A/B, HIV, rheumatoid arthritis and samples tested negative for the same diseases and also Crimean Congo haemorrhagic fever, West Nile fever encephalitis and Rift Valley fever were part of national public health surveillance program of the Senegalese Ministry of Social Action and Health performed in collaboration with Institut Pasteur de Dakar. Therefore, consultation with ethics committee was not required. Pre-COVID-19 samples for malaria endemic areas were from a longitudinal cohort survey performed in Dielmo village and approved by the Senegalese National Ethics Committee for Research in Health (reference number 00000007/MSAS/CNERS/Sec 26 January 2021). Samples from COVID-19 RT-PCR positive patients were obtained from a multicentre cohort survey approved by the Senegalese National Ethics Committee for Research in Health (reference number 00000068/MSAS/CNERS/Sec, 10 April 2020).

Use of Canine Olfactory Detection for Covid-19 Testing Study on U.A.E. Trained Detection Dog Sensitivity

This study aimed to evaluate the sensitivity of 21 dogs belonging to different united arab emirate administrations, trained for covid-19 olfactory detection. The study involved 17 explosives detection dogs, two cadaver detection dogs and two dogs with no previous detection training. Training lasted two weeks before starting the validation protocol. Sequential five and seven- cone line-ups were used with axillary sweat samples from 151 symptomatic covid-19 individuals (sars-cov-2 pcr positive) and from 110 asymptomatic covid-19 negative individuals (sars-cov-2 pcr negative). Each line-up had one positive sample and at least one negative sample. The dog had to mark the positive sample, randomly positioned behind one of the cones. The dog, handler and data recorder were blinded to the positive sample location. The calculated overall sensitivities were between 71% and 79% for three dogs, between 83% and 87% for three other dogs and equal to or higher than 90% for the remaining 15 dogs (more than two thirds of the 21 dogs). After calculating the overall sensitivity for each dog using all line- ups, “matched” sensitivities were calculated only including line-ups containing covid-19 positive and negative samples strictly comparable on confounding factors such as diabetes, anosmia, asthma, fever, body pain, diarrhoea, sex, hospital, method of sweat collection and sampling duration. Most of the time, the sensitivities increased after matching. Pandemic conditions in the U.A.E.., associated with the desire to use dogs as an efficient mass-pretesting tool has already led to the operational deployment of the study dogs. Future studies will focus on comparatives fields-test results including the impact of the main covid-19 comorbidities and other respiratory tract infections.

Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study.

The aim of this proof-of-concept study was to evaluate if trained dogs could discriminate between sweat samples from symptomatic COVID-19 positive individuals (SARS-CoV-2 PCR positive) and those from asymptomatic COVID-19 negative individuals. The study was conducted at 2 sites (Paris, France, and Beirut, Lebanon), followed the same training and testing protocols, and involved six detection dogs (three explosive detection dogs, one search and rescue dog, and two colon cancer detection dogs). A total of 177 individuals were recruited for the study (95 symptomatic COVID-19 positive and 82 asymptomatic COVID-19 negative individuals) from five hospitals, and one underarm sweat sample per individual was collected. The dog training sessions lasted between one and three weeks. Once trained, the dog had to mark the COVID-19 positive sample randomly placed behind one of three or four olfactory cones (the other cones contained at least one COVID-19 negative sample and between zero and two mocks). During the testing session, a COVID-19 positive sample could be used up to a maximum of three times for one dog. The dog and its handler were both blinded to the COVID-positive sample location. The success rate per dog (i.e., the number of correct indications divided by the number of trials) ranged from 76% to 100%. The lower bound of the 95% confidence interval of the estimated success rate was most of the time higher than the success rate obtained by chance after removing the number of mocks from calculations. These results provide some evidence that detection dogs may be able to discriminate between sweat samples from symptomatic COVID-19 individuals and those from asymptomatic COVID-19 negative individuals. However, due to the limitations of this proof-of-concept study (including using some COVID-19 samples more than once and potential confounding biases), these results must be confirmed in validation studies.

Thirty-Day Mortality and Morbidity in COVID-19 Positive vs. COVID-19 Negative Individuals and vs. Individuals Tested for Influenza A/B: A Population-Based Study.

Background: As of October 2020, COVID-19 has caused 1,000,000 deaths worldwide. However, large-scale studies of COVID-19 mortality and new-onset comorbidity compared to individuals tested negative for COVID-19 and individuals tested for influenza A/B are lacking. We investigated COVID-19 30-day mortality and new-onset comorbidity compared to individuals with negative COVID-19 test results and individuals tested for influenza A/B.Methods and findings: This population-based cohort study utilized electronic health records covering roughly half (n = 2,647,229) of Denmark's population, with nationwide linkage of microbiology test results and death records. All individuals ≥18 years tested for COVID-19 and individuals tested for influenza A/B were followed from 11/2017 to 06/2020. Main outcome was 30-day mortality after a test for either COVID-19 or influenza. Secondary outcomes were major comorbidity diagnoses 30-days after the test for either COVID-19 or influenza A/B. In total, 224,639 individuals were tested for COVID-19. To enhance comparability, we stratified the population for in- and outpatient status at the time of testing. Among inpatients positive for COVID-19, 356 of 1,657 (21%) died within 30 days, which was a 3.0 to 3.1-fold increased 30-day mortality rate, when compared to influenza and COVID-19-negative inpatients (all p < 0.001). For outpatients, 128 of 6,263 (2%) COVID-19-positive patients died within 30 days, which was a 5.5 to 6.9-fold increased mortality rate compared to individuals tested negative for COVID-19 or individuals tested positive or negative for influenza, respectively (all p < 0.001). Compared to hospitalized patients with influenza A/B, new-onset ischemic stroke, diabetes and nephropathy occurred more frequently in inpatients with COVID-19 (all p < 0.05).Conclusions: In this population-based study comparing COVID-19 positive with COVID-19 negative individuals and individuals tested for influenza, COVID-19 was associated with increased rates of major systemic and vascular comorbidity and substantially higher mortality. Results should be interpreted with caution because of differences in test strategies for COVID-19 and influenza, use of aggregated data, the limited 30-day follow-up and the possibility for changing mortality rates as the pandemic unfolds. However, the true COVID-19 mortality may even be higher than the stated 3.0 to 5.5-fold increase, owing to more extensive testing for COVID-19.

Clonal Hematopoiesis and COVID-19 Severity in Cancer Patients

Background: Advanced age, medical co-morbidities and a pro-inflammatory immunologic profile are associated with severe COVID-19. Acquired somatic mutations in hematopoietic stem cells (clonal hematopoiesis or CH) are common in elderly individuals. Previous studies have shown CH is associated with alterations in immunologic repertoire and function. Here, we investigate whether CH predisposes to severe COVID-19 or other infections.Methods: We performed a retrospective cohort study of 39,291 adult cancer patients with non-hematologic malignancies who had their tumor and blood sequenced using a panel of 468 known cancer driver genes. We identified individuals who tested positive for SARS-CoV-2 between March 8, 2020 and June 9, 2020. We determined the association between CH and severe COVID-19 (hypoxic event, hospitalization or death) using multivariable logistic regression models. We used an established aggregation schema for ICD-CM codes to identify distinct infection subtypes. The relationship between CH and risk of incident infections was determined using multivariable Cox regression.Results: In the study cohort, 436 patients were positive for SARS-CoV-2 and 165 developed severe COVID-19. COVID-19 patients with CH were more likely to develop severe disease compared to non-severe (OR=1.8; 95% CI: 1.1-2.9; p=0.01). CH was also more common among patients with severe COVID-19 compared to COVID-19 negative individuals (OR=1.6, 95% CI: 1.2-2.4, p=0.01). In 62,891 person-years of follow-up, 4,059 individuals developed an infection. CH was associated with risk of sepsis (HR=1.13; 95% CI 1.01-1.25, p=0.04) and bacterial enteritis (HR=1.8, 95% CI 1.1-2.8, p=0.01).Conclusions: CH is associated with severe COVID-19 and an increased risk of other infections in cancer patients.DisclosuresBolton:GRAIL: Research Funding. Jee:MDSeq Inc.: Patents & Royalties. Papaemmanuil:Celgene: Consultancy, Honoraria, Research Funding; Prime Oncology: Consultancy, Honoraria; Illumina: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSKCC: Patents & Royalties; Kyowa Hakko Kirin: Consultancy, Honoraria; Isabl: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees. Berger:Illumina: Research Funding; Grail: Research Funding; Roche: Consultancy. Levine:Prelude Therapeutics: Research Funding; Qiagen: Current equity holder in publicly-traded company, Membership on an entity’s Board of Directors or advisory committees; Loxo: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Isoplexis: Current equity holder in private company, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Honoraria; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Novartis: Consultancy; Amgen: Honoraria; Gilead: Honoraria. Zehir:Illumina: Honoraria; Memorial Sloan Kettering Cancer Center: Current Employment.