Acute infections were defined as positive SARS-CoV-2 PCR; ten individuals hospitalized with vaccine breakthrough infections; This case is considered as invalid as reported serious adverse event COVID-19 is inclusion criteria of this study.  This is a literature report.  Vaccines against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been demonstrated to be highly effective in preventing symptomatic infections with Coronavirus Infectious Disease 2019 (COVID-19) (1,2). Despite high vaccine efficacy, a small number of breakthrough infections are to be expected. As of 30 April 2021, the Centers for Disease Control and Prevention (CDC) reported 995 acute care hospitalizations for vaccine breakthrough infections (3). However, to date there have been limited data regarding the risk factors for these patients, and no reported serologic COVID-19 testing upon hospitalization. Between 30 December 2020 and 1 April 2021, the System vaccinated more than 25,000, representing over 55% of its eligible patient base. In March 2021, the State experienced a surge of COVID-19, driven largely by the novel B.1.1.7 (Alpha) variant (4). In this observational case series report, we describe all ten cases of SARS-CoV-2 vaccine breakthrough infections diagnosed in hospitalized patients during this time period with the goal of identifying possible patient risk factors as well as serologic responses at the time of admission. Electronic medical records of BNT162b2 (Pfizer-BioNTech) or mRNA-1732 (Moderna) vaccinated patients admitted to the facility with newly diagnosed COVID-19 between 15 March 2021 and 15 April 2021 were reviewed. Patients were included if two or more weeks had elapsed since receipt of the second vaccine dose. Patient factors were collected including medical comorbidities, body mass index (BMI), immunosuppression defined as immunocompromising conditions or treatments, vaccination dates, admission date, presenting symptoms, peak supplemental oxygen requirement, highest level of hospital care needed, status at discharge (living or deceased), and COVID-19 laboratory testing including polymerase chain reaction (PCR) with cycle threshold (Ct) if known (Cepheid), SARS-CoV-2 antigen, and semiquantitative IgM anti-spike(S) and IgG anti-nucleocapsid(N) protein antibody assays. Based on COVID-19 laboratory testing, patients were determined to have acute infection or resolving/resolved infection. Acute infections were defined as positive SARS-CoV-2 PCR, with either Ct values 30, and the presence of anti-N IgG antibodies. This combination of laboratory results was interpreted as consistent with resolving/resolved infection, because anti-N IgG antibodies correlate with neutralizing activity (5) and appear approximately 10 to 14 days after initial infection (6), and Ct values inversely correlate with viral density (7). Presence of anti-N IgG antibodies with high Ct values suggests an expected further decrease in viral load and improvement in symptoms (8). Resolving/resolved infections could include COVID-19 infections greater than 10 days from initial infection, but they could also include remote COVID-19 infections with persistently positive PCR tests. In cases with indeterminate results (e.g., negative anti-N IgG antibodies and a high Ct value), clinical correlation was used to define whether the case was representative of an acute or resolving/resolved infection. The administering clinic of record and staff were also noted. During the study period, twenty patients were hospitalized with COVID-19, of which ten were fully vaccinated (7 BNT162b2 and 3 mRNA-1273) (Table). The mean time between second vaccination dose and diagnosis of COVID-19 was 49 days. All patients with vaccine breakthrough infections were older than 70 years of age. Six had a BMI greater than 30 kg/m2 , all had multiple medical comorbidities, and one was immunosuppressed on nintedanib. Six individuals (patients 1, 2, 3, 5, 9, 10) had acute infections, of which five developed severe COVID-19 necessitating supplemental oxygen. Three individuals (patients 6, 7, 8) had resolving/resolved infections, of which two were admitted for conditions unrelated to their newly diagnosed COVID-19 infection (bacterial endocarditis, axillary abscess). The third individual (patient 6) was admitted for a concern of weakness, but never required oxygen supplementation to suggest a moderate to severe COVID-19 infection. One individual (patient 4) was indeterminate, with a positive PCR, high Ct value, negative antigen, and absent IgM and IgG antibodies. Based on clinical presentation, this was favored to represent early acute infection rather than resolving/resolved infection without serologic response. All individuals were vaccinated through the agency, and there was no obvious relationship among vaccine breakthrough infection, vaccination location, administration date, and vaccinating personnel. Our case series examines patients hospitalized with SARS-CoV-2 vaccine breakthrough infections, in the context of a highly vaccinated population during a COVID-19 surge. The ten hospitalized with vaccine breakthrough infections were elderly, had substantial comorbid conditions, and were often obese. One patient was on immunosuppressive therapy. Given that high risk individuals are more likely to have a diminished humoral response to the SARS-CoV-2 vaccine and subsequently an elevated risk of severe COVID-19 infection, might post vaccination antibody testing be used in this population to determine those with diminished vaccination response so that they could be encouraged to continue precautions? Currently the Food and Drug Administration (FDA) recommends against routine antibody testing to assess immunity after SARS-CoV-2 vaccination (16). However, without a better understanding of vaccine response, many high risk individuals could be at even greater risk as mitigation measures are relaxed (e.g., mandatory masking) for the fully vaccinated. For highrisk individuals, the selective use of antibody testing for anti-S IgM and IgG may be useful to identify those that would benefit from enhanced precautions to SARS-CoV-2 exposure. it is noteworthy that only one individual was hospitalized in their study. While patients with breakthrough infections may tend to have milder symptoms, some will still develop severe symptoms that necessitate hospitalization. Our experience with patients demonstrates that despite higher than average vaccination rates within this population, surging case counts within the community will lead to an increase in breakthrough infections and hospitalizations. As the Delta strain and other highly virulent strains become more prevalent, this report reinforces the need to not only rapidly vaccinate entire communities, but also practice other risk mitigation strategies if local COVID-19 case volumes are high.There are also limitations to this case series, such as the lack of genomic sequencing to detect variants. Laboratory testing included anti-S IgM and anti-N IgG antibodies, but not anti-S IgG antibodies, which would have helped better define humoral response to the vaccine, given limited knowledge of IgM antibody persistence beyond eight weeks. Serial serologic testing was not done to determine the trajectory of an individuals antibody response. This may have helped to further characterize certain cases such as patient 7 who had a resolving/resolved infection but a negative anti-S IgM antibody. Immune protection also involves both serologic and cellular mechanisms, and further research is required to better understand the importance of either. In summary, we report ten patients with SARS-CoV-2 vaccine breakthrough infections requiring hospitalization, including those with acute infection but without observed serologic response, a majority of whom developed severe disease. Our experience suggests that even as vaccination rates climb nationwide, breakthrough infections may continue to occur, especially amidst variant strains and new COVID-19 surges. Additional understanding of factors leading to vaccine breakthrough infection is critical to guide risk mitigation strategies and to help care for those who require acute care hospitalization. Finally, the potential role of serologic antibody testing to identify high risk individuals or to tailor hospital infection control policies should be explored.  TABLE. SUMMARY OF 10 FULLY VACCINATED HOSPITALIZED WITH COVID-19  Patient Number: 2* Age (years): 71 Body Mass Index (kg/m2): 32 Medical Comorbidities: CHF, COPD, DM, IPF Immune system suppression: Yb Presenting Symptoms: Dyspnea, LE swelling Vaccine Series Received: Pfizer Days Between 2nd Vaccine Dose and Hospitalization: 63 COVID-19 Laboratory Testing:  PCRc Status (Ct): Positive (--) Antigen Statusd: Positive Anti-S IgMe (nl, 0- 0.99): 0.13 Anti-N IgGe (nl, 0- 1.39): 0.11 Results Interpretation: Acute infection Peak Supp Oxygen Need (L/min): Mech Vent Peak Hospital Level of Care: ICU Status at Hospital Discharge: Deceased  Follow-up(17Nov2022): This is a literature report. This is a follow-up report based on the receipt of the publication; the case has been updated to include additional information identified in the publication.  Updated information: Literature information was updated.  Vaccines against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been demonstrated to be highly effective in preventing symptomatic infections with Coronavirus Infectious Disease 2019 (COVID-19) (1,2). Despite high vaccine efficacy, a small number of breakthrough infections are to be expected. As of 30 April 2021, the Centers for Disease Control and Prevention (CDC) reported 995 acute care hospitalizations for vaccine breakthrough infections (3). However, to date there have been limited data regarding the risk factors for these patients, and no reported serologic COVID-19 testing upon hospitalization. Between 30 December 2020 and 1 April 2021, the System vaccinated more than 25,000, representing over 55% of its eligible patient base. In March 2021, the State experienced a surge of COVID-19, driven largely by the novel B.1.1.7 (Alpha) variant (4). In this observational case series report, we describe all ten cases of SARS-CoV-2 vaccine breakthrough infections diagnosed in hospitalized patients during this time period with the goal of identifying possible patient risk factors as well as serologic responses at the time of admission. Electronic medical records of BNT162b2 (Pfizer-BioNTech) or mRNA-1732 (Moderna) vaccinated patients admitted to the agency with newly diagnosed COVID-19 between 15 March 2021 and 15 April 2021 were reviewed. Patients were included if two or more weeks had elapsed since receipt of the second vaccine dose. Patient factors were collected including medical comorbidities, body mass index (BMI), immunosuppression defined as immunocompromising conditions or treatments, vaccination dates, admission date, presenting symptoms, peak supplemental oxygen requirement, highest level of hospital care needed, status at discharge (living or deceased), and COVID-19 laboratory testing including polymerase chain reaction (PCR) with cycle threshold (Ct) if known (Cepheid), SARS-CoV-2 antigen, and semiquantitative IgM anti-spike(S) and IgG anti-nucleocapsid(N) protein antibody assays. Based on COVID-19 laboratory testing, patients were determined to have acute infection or resolving/resolved infection. Acute infections were defined as positive SARS-CoV-2 PCR, with either Ct values 30, and the presence of anti-N IgG antibodies. This combination of laboratory results was interpreted as consistent with resolving/resolved infection, because anti-N IgG antibodies correlate with neutralizing activity (5) and appear approximately 10 to 14 days after initial infection (6), and Ct values inversely correlate with viral density (7). Presence of anti-N IgG antibodies with high Ct values suggests an expected further decrease in viral load and improvement in symptoms (8). Resolving/resolved infections could include COVID-19 infections greater than 10 days from initial infection, but they could also include remote COVID-19 infections with persistently positive PCR tests. In cases with indeterminate results (e.g., negative anti-N IgG antibodies and a high Ct value), clinical correlation was used to define whether the case was representative of an acute or resolving/resolved infection. The administering clinic of record and staff were also noted. During the study period, twenty patients were hospitalized with COVID-19, of which ten were fully vaccinated (7 BNT162b2 and 3 mRNA-1273) (Table). The mean time between second vaccination dose and diagnosis of COVID-19 was 49 days. All patients with vaccine breakthrough infections were older than 70 years of age. Six had a BMI greater than 30 kg/m2 , all had multiple medical comorbidities, and one was immunosuppressed on nintedanib. Six individuals (patients 1, 2, 3, 5, 9, 10) had acute infections, of which five developed severe COVID-19 necessitating supplemental oxygen. Three individuals (patients 6, 7, 8) had resolving/resolved infections, of which two were admitted for conditions unrelated to their newly diagnosed COVID-19 infection (bacterial endocarditis, axillary abscess). The third individual (patient 6) was admitted for a concern of weakness, but never required oxygen supplementation to suggest a moderate to severe COVID-19 infection. One individual (patient 4) was indeterminate, with a positive PCR, high Ct value, negative antigen, and absent IgM and IgG antibodies. Based on clinical presentation, this was favored to represent early acute infection rather than resolving/resolved infection without serologic response. All individuals were vaccinated through the agency, and there was no obvious relationship among vaccine breakthrough infection, vaccination location, administration date, and vaccinating personnel. Our case series examines patients hospitalized with SARS-CoV-2 vaccine breakthrough infections, in the context of a highly vaccinated population during a COVID-19 surge. The ten hospitalized with vaccine breakthrough infections were elderly, had substantial comorbid conditions, and were often obese. One patient was on immunosuppressive therapy. Given that high risk individuals are more likely to have a diminished humoral response to the SARS-CoV-2 vaccine and subsequently an elevated risk of severe COVID-19 infection, might post vaccination antibody testing be used in this population to determine those with diminished vaccination response so that they could be encouraged to continue precautions? Currently the Food and Drug Administration (FDA) recommends against routine antibody testing to assess immunity after SARS-CoV-2 vaccination (16). However, without a better understanding of vaccine response, many high risk individuals could be at even greater risk as mitigation measures are relaxed (e.g., mandatory masking) for the fully vaccinated. For highrisk individuals, the selective use of antibody testing for anti-S IgM and IgG may be useful to identify those that would benefit from enhanced precautions to SARS-CoV-2 exposure. it is noteworthy that only one individual was hospitalized in their study. While patients with breakthrough infections may tend to have milder symptoms, some will still develop severe symptoms that necessitate hospitalization. Our experience with Michigan Veteran patients demonstrates that despite higher than average vaccination rates within this population, surging case counts within the community will lead to an increase in breakthrough infections and hospitalizations. As the Delta strain and other highly virulent strains become more prevalent, this report reinforces the need to not only rapidly vaccinate entire communities, but also practice other risk mitigation strategies if local COVID-19 case volumes are high.There are also limitations to this case series, such as the lack of genomic sequencing to detect variants. Laboratory testing included anti-S IgM and anti-N IgG antibodies, but not anti-S IgG antibodies, which would have helped better define humoral response to the vaccine, given limited knowledge of IgM antibody persistence beyond eight weeks. Serial serologic testing was not done to determine the trajectory of an individuals antibody response. This may have helped to further characterize certain cases such as patient 7 who had a resolving/resolved infection but a negative anti-S IgM antibody. Immune protection also involves both serologic and cellular mechanisms, and further research is required to better understand the importance of either. In summary, we report ten patients with SARS-CoV-2 vaccine breakthrough infections requiring hospitalization, including those with acute infection but without observed serologic response, a majority of whom developed severe disease. Our experience suggests that even as vaccination rates climb nationwide, breakthrough infections may continue to occur, especially amidst variant strains and new COVID-19 surges. Additional understanding of factors leading to vaccine breakthrough infection is critical to guide risk mitigation strategies and to help care for those who require acute care hospitalization. Finally, the potential role of serologic antibody testing to identify high risk individuals or to tailor hospital infection control policies should be explored.  TABLE. SUMMARY OF 10 FULLY VACCINATED HOSPITALIZED WITH COVID-19  Patient Number: 2* Age (years): 71 Body Mass Index (kg/m2): 32 Medical Comorbidities: CHF, COPD, DM, IPF Immune system suppression: Yb Presenting Symptoms: Dyspnea, LE swelling Vaccine Series Received: Pfizer Days Between 2nd Vaccine Dose and Hospitalization: 63 COVID-19 Laboratory Testing:  PCRc Status (Ct): Positive (--) Antigen Statusd: Positive Anti-S IgMe (nl, 0- 0.99): 0.13 Anti-N IgGe (nl, 0- 1.39): 0.11 Results Interpretation: Acute infection Peak Supp Oxygen Need (L/min): Mech Vent Peak Hospital Level of Care: ICU Status at Hospital Discharge: Deceased.  Pfizer is a marketing authorization holder of BNT162B2 in the country of incidence or the country where the product was purchased (if different). This may be a duplicate report if another marketing authorization holder of BNT162B2 has submitted the same report to the regulatory authorities.; Sender's Comments: Based on known drug safety profile, there is reasonable possibility of causal association between the event vaccination failure and covid-19 and bnt162b2. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.; Reported Cause(s) of Death: Acute infections were defined as positive SARS-CoV-2 PCR; ten individuals hospitalized with vaccine breakthrough infections