key: cord-0810154-tzg4c9hz authors: Beyoglu, Muhammet Ali; Sahin, Mehmet Furkan; Turkkan, Sinan; Basaran, Fatmanur Celik; Yazicioglu, Alkin; Bektas, Serife Gokbulut; Tekce, Yasemin Tezer; Yekeler, Erdal title: Vaccine Breakthrough Severe COVID-19 in a Lung Recipient date: 2021-11-12 journal: Transplant Proc DOI: 10.1016/j.transproceed.2021.11.003 sha: 9d6a9382b76be57c5bd77e0c310cfd9a6c6eaca6 doc_id: 810154 cord_uid: tzg4c9hz The vaccines developed against Severe acute respiratory syndrome coronavirus type 2 are seen as the most crucial weapon in controlling the epidemic. It has been reported in early-stage vaccine studies that vaccines provide up to 95% protection against severe disease and mortality, even in the absence of symptomatic infection. Reports on vaccine breakthrough infections that developed after widespread vaccination are available in the literature. In addition to the general population, the course of vaccine breakthrough infections in immunocompromised patients is a matter of concern. This case report aimed to define severe COVID-19 developing in a lung recipient who received three doses of inactivated virus vaccine. Conflict of interest statement: The authors declare that they have no conflict of interest. Funding of the article : This article was not financially supported by any company. Informed consent was obtained from the relatives of the patients. Although almost two years have passed since the first case was detected, ongoing social isolation measures and the widespread use of vaccines, the COVID-19 pandemic continues to cause morbidity and mortality worldwide. Re-infections and vaccine breakthrough infections are reported with a frequency that cannot be named as sporadic. Immunocompromised patients are given priority in vaccination programs in our country, as in the rest of the world. The actual rate and prognosis of vaccine breakthrough infections in this patient group is a matter of curiosity. Lung recipients constitute a unique group among immunocompromised patients. Both the intensive use of immunosuppressants and the fact that the main target of the pandemic agent is allograft creates concerns about the course of COVID-19 in lung recipients [1] . In his routine tests two months later, SARS-Cov-2 spike protein-specific immunoglobulin (IgG and IgM) was found to be low positive in the serum. The patient was vaccinated with a third dose of Sinovac in July. Seven weeks after the third dose of Sinovac, the patient, who developed shivering and fever, was applied to the emergency department. The patient's oxygen saturation was measured as 96 in room air, with a temperature of 36.2 °C, pulse rate of 80/min and respiratory rate of 14/min. Chest X-ray was evaluated as normal, and the SARS-Cov-2 RT-PCR test was found positive from the nasopharyngeal swab. The patient with moderate symptoms was followed up on an outpatient basis. Mycophenolate mofetil treatment was interrupted, and favipiravir (2x1600 mg loading on the first day, 2x600 mg on the next four days) and paracetamol were prescribed. The patient, who developed dyspnea on the third day after diagnosis, was again applied to the emergency department. Oxygen saturation was 92 in room air, heart rate was 96/min, and respiratory rate was 18/min. The patient, who was consulted to our center with the current findings, was transferred from the external center. Respiratory examination revealed bilateral wheezing. Throat, tracheal aspirate, blood and urine cultures were taken from the patient. Cytomegalovirus and aspergillus DNA PCR and galactomannan antigen tests from tracheal aspirate and serum samples were negative. Subsegmental atelectasis and bilateral multifocal ground-glass areas predominantly located peripherally were detected on thorax CT (Figure 1) . Nasal oxygen at 4lt/min, empirical antibiotics (meropenem 2x1000mg), ascorbic acid (2x 500mg), enoxaparin sodium (2x40mg) and methylprednisolone (1mg/kg-day) were started for the patient who was hospitalized and followed up in the COVID-19 service. There was no growth in the throat, tracheal aspirate, blood and urine cultures. High-flow oxygen therapy was started on the third day of hospitalization for the patient whose respiratory failure gradually increased. Pulse steroid therapy (3x1000 mg/day methylprednisolone, gradually reduced to maintenance dose) was planned for the patient. Voriconazole (2x 200 mg), amphotericin-B (3x10 mg with a nebulizer) and ganciclovir (2x200 mg) were started empirically. Since respiratory failure could not be managed despite high flow oxygen therapy, invasive mechanical ventilation was applied to the patient. The patient died on the 19th day of hospitalization due to multi-organ failure and septic shock. Delta variant was detected in the naso-oropharyngeal swab sample. Widespread use of effective and safe vaccines is a crucial factor in ending the COVID-19 pandemic. For this purpose, the World Health Organization has given emergency use approval to various SARS-Cov-2 vaccines One of the important causes of vaccine breakthrough infections is the low neutralizing antibodies after vaccination. The vaccine response is expected to be low, especially in the elderly population and immunosuppressed patients [4] . However, the literature has also reported that vaccine breakthrough SARS-Cov-2 infection is seen despite the high neutralizing antibodies [5] . Immune escape mutations in the spike protein of SARS-CoV-2 are highly likely to cause re-infection and vaccine breakthrough infections. Currently, WHO describes four variants as variants of concern and labelled as alpha, beta, gamma, and delta [6]. Vaccine breakthrough infections are seen in the community with SARS-Cov-2 variants that are more contagious, cause more severe disease and have decreased neutralization with antibodies due to previous disease or vaccination, are reported with a frequency that cannot be called sporadic. High mortality rates ranging from 14-34% have been reported in studies on COVID-19 in lung recipients, which are few in the literature [7] [8] [9] . The success of promising treatments such as convalescent plasma, tocilizumab and anakinra in the early stages of the pandemic has not been demonstrated in randomized controlled trials [10] [11] [12] [13] . The lack of an effective treatment regimen raises concerns about vaccine efficacy and infections with mutant SARS-Cov-2 variants in lung recipients, as in other immunosuppressed patients [14] . Due to immunosuppressants, the antibody response may be low, and the risk of vaccine-breakthrough infection is higher in these patients than in the general population. In its consensus document published on 13 August 2021, ISHLT recommended administering a third dose of COVID-19 vaccine to patients undergoing thoracic organ transplantation, regardless of neutralizing antibody level [15] . In our country, only inactivated virus vaccine has been available since the last months of 2020. Therefore, two doses of inactivated virus vaccine were administered to lung recipients. Afterwards, although mRNA vaccines were also provided and recommended to lung recipients, some preferred the inactivated virus vaccine for the third dose. This case is unique in that three doses of inactivated virus vaccine were administered. This is the first case reported in the English literature that vaccine breakthrough infection developed in a lung recipient after three doses of inactive virus vaccine to the best of our knowledge. As a result, the efficacy of inactivated SARS-Cov-2 vaccines in lung recipients may be far below expectations. Although the SARS-Cov-2 infection that develops in these patients starts with mild symptoms, it can progress rapidly. Even if the inactivated SARS-Cov-2 vaccine is fully administered in lung recipients, they should not compromise isolation measures. COVID-19 in a Lung Transplant Patient: Rapid Progressive Chronic Lung Allograft Dysfunction Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: a test-negative casecontrol study Understanding immunosenescence to improve responses to vaccines Report: Infection With SARS-CoV-2 in the Presence of High Levels of Vaccine-Induced Neutralizing Antibody Responses COVID-19 in Lung Transplant Recipients COVID-19 in solid organ transplant: A multi-center cohort study COVID-19 in lung transplant recipients: A single center case series from New York City Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak Tocilizumab in Hospitalized Patients with Severe Covid-19 Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial COVID-19 in lung transplant recipients: A single-center experience