key: cord-0838514-yo8wzj7w authors: Ali, Ayad M.; Ali, Kameran Mohammed; Fatah, Mohammed Hassan; Tawfeeq, Hassan Mohammad; Rostam, Hassan Muhammad title: SARS-CoV-2 Reinfection in Patients Negative for Immunoglobulin G Following Recovery from COVID-19 date: 2021-08-02 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2021.100926 sha: 081cde5ad129426a8a2ee0a1d70b41e2d4bcb716 doc_id: 838514 cord_uid: yo8wzj7w While many patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eventually produce neutralising antibodies, the degree of susceptibility of previously infected individuals to reinfection by SARS-CoV-2 is currently unknown. To better understand the impact of the immunoglobulin (IgG) level on reinfection in recovered coronavirus disease 2019 (COVID-19) patients, anti-nucleocapsid IgG levels against SARS-CoV-2 were measured in 829 patients with previously confirmed infection just after their recovery. Notably, 87 of these patients had no detectable IgG concentration. While there was just one case of asymptomatic reinfection 4.5 months after the initial recovery amongst patients with detectable anti-nucleocapsid IgG levels, 25 of the 87 patients negative for anti-nucleocapsid IgG were reinfected within one to three months after their first infection. Therefore, patients who recover from COVID-19 with no detectable anti-nucleocapsid IgG concentration appear to remain more susceptible to reinfection by SARS-CoV-2, with no apparent immunity. Also, although our results suggest the chance is lower, the possibility for recovered patients with positive anti-nucleocapsid IgG findings to be reinfected similarly exists. Coronavirus disease 2019 is an infectious disease caused by a 2019 novel coronavirus 30 2019-nCoV (1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was named so 31 given the similarity of its symptoms to those induced by severe acute respiratory syndrome (2). Since 32 the first reports of a viral pneumonia of unknown origin emerged from China in late 2019, this disease 33 has spread across the world, with new cases reported daily. The clinical manifestations of COVID-19 34 range widely from asymptomatic to mild, moderate and rapidly progressive severe (pneumonia) 35 disease that can lead to death in some individuals (3) (4) (5) . The moderate clinical symptoms of patients 36 with COVID-19 include fever, dyspnoea, fatigue, dry cough, myalgia and pneumonia. In severe cases, 37 affected patients may experience acute respiratory failure, septic shock and organ failure that might 38 culminate in death (6, 7). 39 Transmission of SARS-CoV-2 from infected people to others is suggested based on epidemiology and 40 clinical evidence (8, 9) , with even asymptomatic infected individuals suggested to be capable of 41 transmitting the virus (10, 11) . 42 Infection by SARS-CoV-2 leads to a detectable immune response, but the susceptibility of previously 43 infected individuals to reinfection by SARS-CoV-2 is not well understood given the brevity of the 44 worldwide pandemic to date. Generally, infection results in the generation of neutralising antibodies 45 in patients (12) (13). SARS-CoV-2 has the capacity to escape innate immune responses, which allows 46 the pathogen to produce large numbers of copies in primarily infected tissues, usually airway epithelia 47 (14). Principally, patients who recover from infectious diseases such as influenza A virus are usually 48 University (no. 02 on 01/08/2020). In addition, informed consent was obtained from all study 97 participants or a parent and/or legal guardian if the individual was younger than 18 years of age. 98 Our study found that 86 patients tested negative for IgG specific to SARS-CoV-2 after recovery among 100 a population of 829 patients who were infected with SARS-CoV-2 for the first time. Twenty-six patients 101 (14 male and 12 female patients, aged 10-60 years old) were reinfected after recovery with the rate 102 of 3.13%; of these, 25 patients were in the IgG-negative group and only one patient was IgG-positive 103 ( Figure 1) . 104 Just during the first week after recovery, anti-nucleocapsid IgG antibodies against the SARS-CoV-2 105 were found in 96.2% serum of the reinfected patients. Only one patient was reinfected even though 106 his anti-nucleocapsid IgG result remained positive after recovery from COVID-19 (Table 1) . Most IgG-107 negative patients presented with just a couple of signs of COVID-19, including fever (96%) and myalgia 108 (68%) and continued cough (< 15% cases), while reinfected patients suffered more signs including 109 fever (96%), myalgia (88%), continuous cough (88%), anosmia and ageusia together (72%) ( Table 2) . In addition, after reinfection more than 95% of the reinfected COVID-19 seroconvert patients had 111 been protected as evidenced by anti-nucleocapsid IgG antibody induction. Surprisingly, there was no 112 detectable IgG concentration in a male patient who had most of the common signs and symptoms of 113 COVID-19 during both his first infection and reinfection. Also, an immunocompetent male patient (no. 114 26 in Tables 1 and 2) showed serum IgG level of 5.87 s/ca against SARS-CoV-2 nucleocapsid after 115 recovery but was reinfected 138 days later. Interestingly, the reinfection induced his immune system 116 to produce IgG level by amount (2.08 s/ca) less than the first infection. The occurrence of reinfection 117 in the group ranged from 26 to 138 days after recovery from the initial infection (Table 1) that those patients who recovered from SARS-CoV-2 infection with IgG negativity in this study 155 were exposed to a lesser amount of viral antigen. 156 The reinfection rate in the present study was greater than those recorded by Hall, et al. (33) 157 and Graham et al.(34) . SARS-CoV-2 genomic sequences from the reinfection cases in the study 158 J o u r n a l P r e -p r o o f area have not been concluded yet, which raises the expectation of new phylogenetically 159 distinct variants of SARS-CoV-2 that makes them more virulent. 160 The degree of protective immunity conferred by prior infection and the possibility of 161 reinfection by SARS-CoV-2 is not well understood ( with more severe symptoms (22, 32, 35) . In our study, the degree of disease severity in the 169 reinfection period was worse in most patients than that during the first instance of COVID-19. J o u r n a l P r e -p r o o f 218 2. WHO. 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